case study for chronic renal failure

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• Kidney Int Suppl (2011)
• v.10(1); 2020 Mar

Global case studies for chronic kidney disease/end-stage kidney disease care

Chih-wei yang.

1 Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan

David C.H. Harris

2 Centre for Transplantation and Renal Research, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia

Valerie A. Luyckx

3 Institute of Biomedical Ethics and the History of Medicine, University of Zurich, Zurich, Switzerland

4 Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

Masaomi Nangaku

5 Division of Nephrology, The University of Tokyo School of Medicine, Hongo, Japan

Fan Fan Hou

6 State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China

Guillermo Garcia Garcia

7 Servicio de Nefrologia, Hospital Civil de Guadalajara Fray Antonio Alcalde, University of Guadalajara Health Sciences Center, Hospital 278, Guadalajara, Jalisco, Mexico

Hasan Abu-Aisha

8 Almughtaribeen University, Khartoum, Sudan

Abdou Niang

9 Department of Nephrology, Dalal Jamm Hospital, Cheikh Anta Diop University Teaching Hospital, Dakar, Senegal

10 Dialysis Unit, CASMU-IAMPP, Montevideo, Uruguay

Sakarn Bunnag

11 Division of Nephrology, Department of Internal Medicine, Rajavithi Hospital, Bangkok, Thailand

Somchai Eiam-Ong

12 Department of Medicine, Chulalongkorn Hospital, Bangkok, Thailand

Kriang Tungsanga

13 Division of Nephrology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

14 Bhumirajanagarindra Kidney Institute, Bangkok, Thailand

Marie Richards

15 SEHA Dialysis Services, Abu Dhabi, United Arab Emirates

Nick Richards

Bak leong goh.

16 Department of Nephrology and Clinical Research Centre, Hospital Serdang, Jalan Puchong, Kajang, Selangor, Malaysia

Gavin Dreyer

17 Department of Nephrology, Barts Health NHS Trust, London, UK

18 Centre for Nephrology, University College London, London, UK

Henry Mzingajira

19 Malawi Ministry of Health, Queen Elizabeth Central Hospital, Blantyre, Malawi

Ahmed Twahir

20 Parklands Kidney Centre, Nairobi, Kenya

21 Department of Medicine, The Aga Khan University Hospital, Nairobi, Kenya

Mignon I. McCulloch

22 Paediatric Intensive and Critical Unit, Red Cross War Memorial Children’s Hospital, University of Cape Town, Cape Town, South Africa

23 Division of Nephrology, College of Medicine, Seoul National University, Seoul, Korea

Charlotte Osafo

24 School of Medicine and Dentistry, College of Health Sciences, University of Ghana, Legon, Accra, Ghana

Hsiang-Hao Hsu

Lianne barnieh.

25 Department of Medicine, University of Calgary, Calgary, Alberta, Canada

26 Pan American Health Organization/World Health Organization’s Coordinating Centre in Prevention and Control of Chronic Kidney Disease, University of Calgary, Calgary, Alberta, Canada

Jo-Ann Donner

27 International Society of Nephrology, Brussels, Belgium

Marcello Tonelli

The prevalence of chronic kidney disease and its risk factors is increasing worldwide, and the rapid rise in global need for end-stage kidney disease care is a major challenge for health systems, particularly in low- and middle-income countries. Countries are responding to the challenge of end-stage kidney disease in different ways, with variable provision of the components of a kidney care strategy, including effective prevention, detection, conservative care, kidney transplantation, and an appropriate mix of dialysis modalities. This collection of case studies is from 15 countries from around the world and offers valuable learning examples from a variety of contexts. The variability in approaches may be explained by country differences in burden of disease, available human or financial resources, income status, and cost structures. In addition, cultural considerations, political context, and competing interests from other stakeholders must be considered. Although the approaches taken have often varied substantially, a common theme is the potential benefits of multistakeholder engagement aimed at improving the availability and scope of integrated kidney care.

The prevalence of chronic kidney disease (CKD) and its risk factors is increasing worldwide, and there is a rapid rise in global need for the treatment of end-stage kidney disease (ESKD). The global nephrology community recognizes the need for a plan to address the growing incidence of CKD and a cohesive approach for CKD/ESKD integrated care. 1 This provides a major challenge for health systems, particularly in lower-middle-income countries (LMICs). Because of the growing demand for expensive kidney replacement therapy (KRT; dialysis or kidney transplantation) and in light of the limited resources, ESKD care must be prioritized against the prevention and treatment of CKD, acute kidney injury (AKI), and other noncommunicable diseases (NCDs).

Countries are responding to the challenge of ESKD in different ways, with variable provision of the components of a kidney care strategy (effective prevention, detection, conservative care, kidney transplantation, and an appropriate mix of dialysis modalities) and World Bank classification of economic status. 2 A key goal stated in the article by Harris et al. 1 was to identify a representative selection of country-based case studies showing different levels of development in managing CKD/ESKD care, which offers valuable learning examples. This article illustrates the different approaches that 15 countries have taken toward integrated kidney care ( Table 1 ). Specific areas of approach, in distinct contexts, provide unique experience in CKD, dialysis, and transplantation for ESKD care that are appropriate for each country. Variability in approaches may be explained by country differences in burden of disease, available human or financial resources, and cost structures. In addition, cultural considerations, political context, and competing interests from other stakeholders are confounding factors. This created value to appreciate the similarities and differences of approaches among the unique pathways obtained from each country’s cases.

Table 1

Summary of the CKD/ESKD care study cases

CKD, chronic kidney disease; ESKD, end-stage kidney disease; KRT, kidney replacement therapy; PD, peritoneal dialysis.

Finally, the current approach to kidney disease in many countries is neither sufficient nor sustainable. Thus, this series of case studies demands the urgent attention of governments and policymakers in each country to achieve better integrated CKD/ESKD care.

Integrated CKD/ESKD Care Cases

Taiwan (high-income country): evolution of comprehensive integrated ckd/eskd care.

High prevalent rates of CKD have continued in Taiwan and are reported to be 6.9% for CKD stage 3 to 5, 9.83% for clinically recognized CKD, and 11.9% for CKD stage 1 to 5. However, overall awareness of CKD is low. 3 The major underlying kidney diseases contributing to ESKD are diabetes mellitus (43.2%), chronic glomerulonephritis (25.1%), hypertension (8.3%), and chronic interstitial nephritis (2.8%). 4 The national kidney care program was initiated in response to high rates and has been successfully implemented across Taiwan, resulting in improvements in outcomes for patients along with sustainable cost reductions for the health care system. The pathway and evolution of the CKD/ESKD program in Taiwan may serve as a template in countries where CKD/ESKD is an emerging health care burden ( Table 2 and Appendix 1 ).

Table 2

Evolutionary pathway and road map of CKD/ESKD integrated care in Taiwan

CKD, chronic kidney disease; ESKD, end-stage kidney disease.

To monitor the incidence and burden of ESKD, a national dialysis registry was initiated in 1987 by the Taiwan Society of Nephrology. After this, the Taiwan Society of Nephrology proposed to the Department of Health to make CKD prevention and care a major public health priority. Subsequently, an integrated CKD care program was initiated to promote the screening of high-risk populations (according to the risk factor analysis of epidemiology studies), patient education, and multidisciplinary team care. The CKD care program started in major hospitals in the first phase, then extended to 90 institutes in 2009, and finally rolled out to clinics of general practitioners in 2011. To encourage enrollment in the CKD care program, the Bureau of National Health Insurance reimbursed comprehensive pre-ESKD care for patients with CKD stage 3b to 5 since 2007 and has extended coverage to CKD stage 1 to 3a (early CKD) in 2011. 5 , 6 , 7

These efforts to combat CKD in Taiwan involve collaboration among government, academia and their respective societies, and nongovernmental organizations (NGOs) to enable a multidisciplinary approach that targets not just CKD but also upstream drivers such as diabetes, hypertension, and hyperlipidemia.

Since November 2003, widely used nephrotoxic Chinese herbs containing aristolochic acid were prohibited through public health legislation. This important step also contributed to CKD/ESKD prevention in Taiwan.

Dedicated nephrologists are key to the success of the program, as this group is crucial for performing roles ranging from CKD screening, education, and treatment to involvement and negotiation of public health policy. The CKD committee within the Taiwan Society of Nephrology was the core for the promotion of CKD prevention activities in collaboration with the government—including the Taiwan Kidney Day campaign, which started in 2005.

Strategies for CKD/ESKD care

The strategy and road map for CKD/ESKD care in Taiwan include the following:

• • extending the target population from severe CKD to early stages of CKD as well as commencing kidney health promotion in the general population;
• • integration of CKD as a target of pay-for-performance health care improvement projects, along with diabetes and cardiovascular disease;
• • implementation of early detection and surveillance via national annual physical checkup data for early CKD;
• • early referral to proper care clinics/hospitals;
• • promoting health literacy to the general public; and
• • increased attention to those at highest risk: elderly, multiple diseases, polypharmacy, and so on.

Other factors that have affected the incidence and prevalence of ESKD in Taiwan include universal health coverage (UHC) along with collaboration among government, academia, and NGOs with nephrology societies. Further efforts will be on the prevention and reduction of AKI, outcome monitoring, the promotion of CKD/ESKD shared decision-making, and kidney conservative care. Finally, sustainable quality care of patients with ESKD receiving KRT should be maintained as the ultimate goal.

Outcome measures include the stabilization of the incidence of ESKD in those younger than 75 years, along with lower mortality, better quality of care, less medical costs, better quality of life, and slower rate of progression in patients as demonstrated by findings from the pre-ESKD and early CKD integrated care program 5 , 6 , 7 and diabetes care program. 8 Recent progress of ESKD care has evolved to include more shared decision-making within advance care planning to enable patients and families to choose from various supportive or conservative care options (KRT and withholding/withdrawal of dialysis, where appropriate). The era of CKD care has in parallel progressed to include multidisciplinary care alongside cardiac-kidney-diabetes care with involvement from cardiologists, nephrologists, and endocrinologists. Together these specialists evaluate and educate through dietary management, medical treatment, and surgical intervention, with the goal of reducing mortality and complications in patients with CKD/ESKD. A new concept of personalized care for patients with multimorbidities on dialysis was initiated to treat patients with evidence-based medicine according to the recommended guidelines while also adjusting and modifying for more personalized therapy. This approach has resulted in the stabilization of diabetes mellitus as a cause of ESKD in Taiwan and has also reduced the use of analgesics in patients with ESKD in the year before the initiation of dialysis. 9 The involvement of vascular surgeons in the care of patients on dialysis has also resulted in a reduction of vascular access reconstruction rates. The overall 5-year survival rate of patients on dialysis is currently ∼55.2%, which lies between the rates observed in Japan and Europe. Although the rate of transplantation has been low in Taiwan, the recent promotion of living-related kidney transplantation has increased.

Japan (high-income country): a mature integrated CKD/ESKD care system

Strategies and action plans for kidney disease have been discussed and implemented in collaboration with national and local governments, academic societies, nonprofit organizations, and patient groups in Japan.

Strategies for kidney disease in Japan have focused on early diagnosis of kidney disease by health checkups conducted in schools or workplaces, improvement in CKD care, and dialysis therapy. Dialysis therapy has been covered by health insurance since 1967, and patients requiring maintenance dialysis treatment have been exempted from medical expenses since 1972. Kidney transplantation has been covered by health insurance since 1978, and the Organ Transplant Law of Japan was legislated in 1997. The Ministry of Health, Labour and Welfare promotes various areas of research, such as the kidney failure research team (founded in 1989) and the medical care of chronic kidney failure (published guidelines for dialysis initiation in 1991).

Following the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification of Risk, a CKD initiative subcommittee was launched in the Japanese Society of Nephrology (JSN) in 2004. 10 To raise awareness of CKD and its complications to society and promote its measures on a national scale, the Japan Association of Chronic Kidney Disease Initiative was founded by JSN in association with the Japanese Society for Dialysis Therapy and the Japanese Society for Pediatric Nephrology in 2006. Since 2007, Kidney Disease Measures Study Meetings, with participation from physicians, nurses, public health specialists, local government staff, and representatives of kidney disease patient groups, were held by the Ministry of Health, Labour and Welfare. These meetings resulted in the formation of the national action plan of CKD strategies in 2008: Future Kidney Disease Measures to Be Achieved. The aim of the strategies is to slow progression of kidney dysfunction, prevent the need for KRT, decrease the number of patients with incipient kidney failure, and reduce cardiovascular complications from CKD. Specifically, this action plan called for raising awareness and disseminating knowledge, a medical cooperation system, improvement in medical treatment standards, development of human resources, and promotion of research. The Ministry of Health, Labour and Welfare is currently revising the national action plan for CKD through the second Kidney Disease Measures Study Meeting, discussing a new national action plan to reduce the number of patients on incident dialysis below 35,000 per year by 2028.

Japanese scientific societies, including JSN, Japanese Society for Dialysis Therapy, and Japan Medical Association, developed various guidelines for referral and care of patients with kidney disease between general practitioners and nephrologists.

In 2013, the Ministry of Health, Labour and Welfare developed a formal document targeting CKD within the national health promotion agenda (Basic Direction for Comprehensive Implementation of National Health Promotion). This document included numerical targets to reduce the number of patients on incident dialysis due to diabetic kidney disease by 2022.

Since Japan instituted UHC in 1961, all citizens are covered by some kind of health insurance. The Japan Revitalization Strategy 2013, a growth strategy announced by the Japanese government extending the nation’s “healthy life expectancy,” was set as one of the themes. 11 Programs to develop a new system of preventive care and health management will be promoted through the requirement of all health insurance societies to analyze data such as health insurance claims. This project program called Data Health Plan will use health data to maintain and improve health conditions of its subscribers, including reduction in the incidence of dialysis. Concrete plans are needed to prevent the onset and worsening of CKD from lifestyle-related disease, such as diabetes or hypertension, identified in specific medical checkups ( Figure 1 ) 12 instituted in 2008. These specific medical checkups are mandated by individual health insurance companies according to the guidelines that outline appropriate laboratory tests to be included, standard inquiries, and the selection and stratification of individuals who require further health guidance. JSN is continuing to emphasize collaboration with other domestic and international societies and regulatory agencies. JSN also achieved its goal of collaborating with the International Society of Nephrology (ISN) and the Japanese Diabetes Society. 13

Relationship between the basic concept of Data Health Plan and chronic kidney disease (CKD), Japan. Reproduced with permission from [Proposal to achieve a decline in the number of dialysis initiations due to lifestyle related diseases—early detection and prevention of onset and progression of CKD]. Nihon Jinzo Gakkai Shi. 2016;58:429–475 [in Japanese]. 12 Copyright © 2016 Japanese Society of Nephrology.

The number of kidney transplantation procedures has increased from 749 in 2000 to 1598 in 2011 and remains constant in 2016 with 1648 total transplants (of note, 1471 from living donors, 61 from donors after cardiac death, and 16 from donors after neurological death). As a proportion of the general population, these rates are low compared to other high-income countries. Standardized incidence ratios of dialysis have significantly decreased since 2008 in Japan ( Figure 2 ). 14 However, the total number of patients on incident dialysis was projected to increase from 36,797 in 2015 to 40,360 in 2025 because of the aging population.

Incidence rates of dialysis by sex and age group in Japan, 2005–2015. Reproduced with permission from Wakasugi M, Narita I. Evaluating the impact of CKD initiatives on the incidence of dialysis in Japan. Jpn J Nephrol. 2018;60:41–49. 14 Copyright © 2018 Japanese Society of Nephrology and the Japanese Journal of Nephrology.

China (upper-middle-income country): prevention and treatment of ESKD

China is the largest LMIC and is home to 20% of the world’s population. CKD is common in China and is now the fastest growing cause of death. 15 The government’s current NCD policy, along with major national medical research grants, focuses predominantly on 5 diseases—cardiovascular disease, cancer, diabetes, chronic respiratory disease, and mental illness—notably excluding CKD. There is no national program for the prevention and treatment of CKD or chronic dialysis in China, though Chinese nephrologists have made great efforts to reduce the prevalence of ESKD and improve outcomes in this population, particularly during the last decade.

Understanding CKD and ESKD burden

CKD is a rapidly growing health burden and is a huge health care challenge in China. Epidemiological studies show that the prevalence of CKD in Chinese adults is 10.8%, 15 representing a population of 120 million patients. As of 2017, there were ∼1 million patients with ESKD in China, with only 52% of them having access to KRT. 16 Based on the current average treatment cost, the annual health care expenditure on dialysis in China is ∼US$50 billion.

A recent study, the China Renal Biopsy Series, analyzed 71,151 patients who had a kidney biopsy at 1 of 938 hospitals in 282 cities across China from 2004 to 2014. 17 This analysis found that IgA nephropathy was the most common glomerular disease with a standardized frequency of 28% and the leading cause of progressive CKD in all age groups. Furthermore, the risk of membranous nephropathy has increased by 13% annually during the last decade. The latter could be associated with the increased level of air pollution with particulate matter <2.5 μm in diameter, a health problem faced by many developing countries.

With the rapid growth of the economy and changes in lifestyle, the prevalence of diabetes mellitus is significantly increasing in China. 18 This increase has changed the pattern of CKD in China. Since 2011, the percentage of CKD due to diabetes has exceeded that of glomerulonephritis-induced CKD in hospitalized patients. 19

AKI is an important driver of CKD, and in China, the incidence of AKI is 11.6% in hospitalized adults 20 and 19.6% in children, 21 but the detection rate is only 0.99% in hospitalized patients. 22 In addition to other known risk factors, nephrotoxic herbs are a potential risk factor for AKI in Chinese adults.

Developing population-based prevention approaches for CKD/ESKD according to the risk factor in the Chinese population

Epidemiological studies have shown that folic acid deficiency is prevalent in Chinese hypertensive populations, particularly in rural areas, and is associated with the risk of development of CKD. 23 A recent large-scale, multicenter, randomized controlled trial conducted in 20 rural communities in China evaluated the efficacy of folic acid supplementation in the prevention of kidney function loss in a hypertensive population without previous cardiovascular disease. 24 Compared to treatment with enalapril alone, the addition of low-dose folic acid significantly reduced the risk of kidney function decline. In patients with CKD at study enrollment, folate supplementation reduced the risk of CKD progression by 56%. Folic acid therapy was also found to reduce the risk of a first stroke 25 and new-onset albuminuria in patients with diabetes. 26 Because folate deficiency has been reported in other developing countries, 27 supplementation of folic acid would be considered a kidney-protective approach for hypertensive populations in these regions.

Developing intervention approaches for delaying progression of CKD in China

Once CKD progresses to ESKD, the risk of death and medical costs increase exponentially. Delaying progression of CKD toward ESKD is an important strategy for reducing the burden of ESKD, particularly in LMIC with limited medical resources. The efficacy of renoprotection by angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with CKD has been demonstrated in randomized controlled trials. 28 , 29 Angiotensin-converting enzyme inhibitors can even be administered in patients with CKD stage 4 and delays the onset of ESKD from 3.5 to 7 years. 30 Uptitration of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker dosages against albuminuria confers further benefit on kidney outcomes in patients with nondiabetic CKD and kidney insufficiency. 31 Given the ∼80,000 patients initiating dialysis every year in China, the uptake of these therapies could save US$120 million annually by delaying dialysis by 1 year for each patient.

Promoting home-based KRT in China

The number of patients on peritoneal dialysis (PD) in China rose from 37,942 in 2012 to 55,373 in 2014. 32 China also has the largest variation in PD uptake among regions, ranging from 14% in mainland China to 73% in Hong Kong. 33 The PD-First policy implemented by Hong Kong health authority may contribute to the higher rate of PD uptake. PD has been recommended as a preferred KRT because of its lower cost, reduced requirement for technical support, and less need for trained medical staff. Increasing access to PD could help increase access to KRT for patients with ESKD, particularly in LMIC.

There are still challenges in delivering PD to patients with ESKD living in rural areas with less access to medical care and dialysis. The Flying Angel program is a model developed by a partnership between the Chinese government, medical centers, and the PD industry to overcome the barriers of promoting PD in rural China. 34 This program develops collaboration between central hospitals and community clinics, provides PD training for community medical practitioners, and has a delivery system for PD fluid and materials. This program has increased access to KRT for rural patients with ESKD. 34

The optimal management of home-based PD is critical for reducing the risk of failure and improving outcomes. By implementing a telephone hotline and mobile phone applications, the collaboration between central hospitals and community clinics is strengthened further, facilitating communication between physicians and patients on PD. Home-based management systems, which include mobile phone applications, also provide lifestyle modification guidance for patients and collects information on treatment response from patients. This model of care increases the compliance of patients on PD and decreases the cost associated with hospital and physician visits.

Mexico (upper-middle-income country): moving toward universal access of CKD/ESKD care

Mexico’s health system does not offer UHC for patients with kidney disease. Social security benefits, including universal access to dialysis and kidney transplantation, are available to individuals employed by the private sector or by the government. However, more than half of the population does not have access to social security benefits and cannot afford private health care services. Access to dialysis and kidney transplantation for this population is limited or nonexistent. 35

To reduce health disparities, a constitutional reform was introduced in 1983, recognizing the right of Mexicans to access health insurance. 36 In 1984, legislation on organ and tissue donation and transplantation was passed by the Mexican congress, including the setup of the National Transplantation Registry, to coordinate and facilitate organ procurement and transplantation. In the 1990s, a network of state transplant coordinators and associated organizations were organized throughout the country, as well as a central coordinating center, the National Transplant Center (CENATRA in Spanish). 37

In 2000, a workshop was convened by the Ministry of Health (MOH) to organize a national dialysis registry, with the participation of representatives of all 32 Mexican state health secretariats; members of the Mexican Society of Nephrology, the Mexican Institute for Nephrology Research, the Mexican Board of Nephrology, and Jalisco Dialysis and Transplant Registry; the directors of the Canadian Organ Replacement Registry and the United States Renal Data System. After this, an ad hoc steering committee began a series of meetings at the MOH’s National Directorate of Epidemiology to set up the registry 38 and a number of actions for the prevention and control of CKD were included in Mexico’s National Health Plan 2001–2006. 39 Among them was the implementation of early screening and treatment of CKD along with a national dialysis registry.

In 2003, a structural reform of the Mexican health system increased financial protection of its citizens by offering publicly subsidized health insurance to more than half of the population not covered by social security. The center of the reform was the creation of Seguro Popular (Popular Health Insurance), 40 which divides personal health services into essential packages of interventions financed by the Fund for Protection against Catastrophic Health Expenditures (FPGC). 41 The law came into effect on January 1, 2004, and dialysis and organ transplantation were among the 7 high-cost interventions included in the FPGC. In 2010, the MOH set up the Strategic Health Services Network Against Chronic Kidney Disease, emphasizing the need for early detection and treatment of CKD. 42

In 2015, the Mexican Health Foundation (FUNSALUD in Spanish) began organizing a series of meetings with representatives from Mexico’s health systems and members of the Mexican nephrology societies to reinitiate the setup of the dialysis registry, which had been abandoned by Mexican health authorities. After the ISN Global Kidney Policy Forum held at the ISN World Congress of Nephrology 2017 in Mexico City, the MOH implemented the pilot testing of the National Registry of Chronic Kidney Disease (RENERC in Spanish) as part of the nation’s health information system.

Thirty-five years after the constitutional reform of 1983, universal access to kidney care is yet to be realized. Since the implementation of Seguro Popular, the proportion of the population with some type of public health insurance has increased from 41% in 2002 to 81% in 2015 43 and the number of high-cost interventions included in the FPGC has increased from 7 to 68. However, Seguro Popular still does not pay for dialysis. As a result, the marked disparities between the insured and uninsured populations with access to KRT persist. By 2015, the incidence and prevalence of patients receiving treatment for ESKD with social security were 281 and 1357 per million population (pmp), respectively; however, 130 patients pmp on incident dialysis and 200 patients pmp on prevalent dialysis remained uninsured. 35

The introduction of legislation on organ donation and transplantation in 1984 resulted in a significant increase in kidney transplantation rates, from 1.57 pmp in 1984 to 22.8 pmp in 2015. However, this success is not observed in the population without social security. Because Seguro Popular still does not cover the cost of kidney transplantation and immunosuppressive drugs, transplantation rates remain significantly lower in patients without social security. 35

Eight years after the setup of the Strategic Health Services Network Against Chronic Kidney Disease, strategies to prevent CKD are yet to become part of the nation’s NCD health policies. CKD screening is low or nonexistent across Mexico. Furthermore, uninsured patients with predialysis CKD are often denied access to treatment by Seguro Popular once identified as having kidney disease. 35 Therefore, the opportunity to intervene to delay the progression of CKD is lost.

Finally, the dialysis registry is currently under pilot testing with the participation of several dialysis centers. The sustainability and nationwide expansion of the registry are yet to be seen.

Sudan (lower-middle-income country): evolution of strategies for CKD/ESKD care

During the 1970s, a Sudanese patient was treated in London, UK, for kidney failure by hemodialysis (HD). As he decided to continue his treatment under the care of medical staff of the University Hospital of Khartoum, his HD machine was the basis for the first dialysis unit in Khartoum.

Around the same time, a young surgeon by the name of Omar Beliel was sent by the University Hospital of Khartoum to train in England to be a neurosurgeon. While in the United Kingdom, he had kidney failure and eventually he received a kidney donated by his brother. Dr. Beliel later wrote an autobiography titled Two Lives: Death Odyssey of a Transplant Surgeon , 44 in which he describes how kidney transplantation gave him a “second life.” He subsequently shifted his training from neurosurgery to transplant surgery and performed the first kidney transplantation procedure in Africa from a living-related donor in 1974. By the mid-1970s, HD, intermittent PD through the use of hard catheters, and living-related kidney transplantation were established services at the University Hospital of Khartoum. However, these services were limited because of resources and the University Hospital remained mostly an academic and teaching facility.

The 1980s saw an expansion in dialysis services to benefit more patients, which was supported by the Ministry of Finance. It was soon evident that these services were costly and further expansion was unlikely to be feasible.

In 1994, the government called for Expert Opinion Conferences on How-Best-to-Do (HBTD) the civil services. The conferences called on scholars and experts in health, education, economy, and other areas to discuss reform of these issues and make recommendations to be executed by the government. A final recommendation in the area of health was to establish the National Centers of Health Care for 5 key areas: kidney disease, heart disease, oncology, gastroenterology and hepatology, and neurosciences. These national centers were required to plan for health care in their respective areas, along with suggestions and the means for successfully operating across the country. Thus, the National Center for Kidney Diseases and Surgery was established in 1995 and has been responsible for CKD/ESKD care across Sudan for the last 2 decades.

The National Medical Supplies Fund was established hand in hand with the National Centers of Health Care. The main objective was to procure and justly distribute medicines nationwide at the lowest cost. An important issue that resulted from the National Medical Supplies Fund policies was the need to have a national regulation for life-saving medicines (LSM), medicines that should be available to all citizens free of charge. After many discussions, it was agreed that the treatment of ESKD was to be considered a lifesaving issue and therefore both dialysis and kidney transplantation would be covered by the LSM bill. Thanks to this huge step forward, the development of both CKD services as preventive measures and ESKD therapy would be managed under the umbrella of the National Center for Kidney Diseases and Surgery.

Another important contribution to the success of managing CKD/ESKD in Sudan is the National Zakat Fund (NZF), which was established in the 1990s. Zakat is an Islamic concept where Muslims with the financial means are required to contribute 2.5% of their annual income as charity. The current government decided, for the first time, to create an organized institution to then use these funds in an orderly fashion. As the activities of the fund are regularly published, it became a trustworthy organization and most individuals who pay zakat prefer NZF to find suitable recipients of the aid. Religious scholars agreed that treatment of ESKD through dialysis and transplantation would be eligible to be supported by NZF.

In 2005, the National Medical Supplies Fund accepted continuous ambulatory PD as a viable option for treatment of ESKD, particularly for children and young patients. It has since become an option for ESKD management, albeit on a limited scale.

Using funds obtained from the LSM bill and NZF, the National Center for Kidney Diseases and Surgery is able to meet the requirements of providing CKD/ESKD care for citizens in Sudan.

Dialysis facilities and modalities

Sudan is the second largest country in Africa, with a total population of ∼38 million. Nearly all cities and large towns have governmental HD centers to care for patients with ESKD. Currently, the total number of HD centers is 72. There are 7200 patients currently on dialysis; 97% of these are on HD. 45 HD is based on twice weekly sessions for stable patients. The reason for this suboptimal dialysis schedule is to accommodate as many patients with EKSD as possible under the free-of-charge scheme of the national HD system. A recent survey showed that the 1-year survival of patients on twice weekly HD was 83%. 46 Patients who had functioning arteriovenous fistulas did significantly better than those who were dialyzed via cuffed or noncuffed central venous catheters. 46 Availability of continuous ambulatory PD is still limited to the greater Khartoum state. Although only 3% of patients on dialysis are on continuous ambulatory PD, the outcome and quality of life figures are rewarding. If PD fluid could be manufactured locally, ideally more patients on PD could be accommodated.

Kidney transplantation

The kidney transplant activities in Sudan over the last 5 years are increasing. Kidneys are transplanted exclusively from living-related donors. About 80% of the cost of the transplant is covered by either the LSM bill or NZF. All patients (irrespective of where the transplant was done) receive immunosuppressive drugs free of charge.

In summary, the most important milestones in developing a strategy for care for patients with CKD/ESKD in Sudan are as follows:

• • The call by the government in 1994 for national conferences to give advice on how best to do reforms across the country. This resulted in the birth of the National Center for Kidney Diseases and Surgery, which plans and supervises kidney care nationwide.
• • The introduction of the LSM bill was a novel resolution that made it possible to view CKD/ESKD care as a lifesaving issue, using funds to cover almost all citizens free of charge.
• • The Islamic system of zakat that requires eligible Muslims to voluntarily pay 2.5% of their annual income to support the poor or programs designed to help the poor. The addition of CKD/ESKD care to be covered by this fund has helped immensely.

Senegal (lower-middle-income country): fundamental development of CKD/ESKD care

Senegal is a country on the western tip of Africa, with a population of 15 million, and is one of the poorest countries in the world. Nephrology was unknown in Senegal until the return of the first Senegalese nephrologist after the conclusion of his training in France. Over time, a dedicated nephrology curriculum for undergraduate medical students along with HD and kidney biopsy practices has been introduced. Until 2010, however, there were only 2 HD centers in each of the public and private health sectors, dialysis costs were paid out of pocket by patients without health coverage, and there were only 3 nephrologists in the country.

Epidemiology

The prevalence of CKD in Senegal is estimated at 4.9%. 47 The main cause of CKD is hypertension, followed by chronic glomerulonephritis (especially primary focal segmental glomerulosclerosis), diabetes, and the use of traditional nephrotoxic drugs. The World Health Organization STEPwise survey found the prevalence of hypertension and diabetes in the general Senegalese adult population aged 45 to 49 years to be 25% and 5.4%, respectively. Advocacy and increased awareness among political authorities has made it possible to set up an NCD office at the MOH with a focal point on nephrology for the management of kidney disease. UHC was introduced in 2014, which provides free dialysis for Senegalese patients, but with limited availability. The government provides all dialysis supplies and a bundled payment of 10.000 FRFA (US$20) for each dialysis session at public dialysis centers. Patients, when dialysis slots are not available, are registered on the first come, first serve waiting list. In the meantime, to survive, patients must pay out of pocket to receive dialysis in the private sector.

Kidney care

A national and international nephrology referral service has been developed at the largest university hospital in Senegal. An average of 200 kidney biopsies are done each year, with samples processed and read on site. HD began at the largest public HD center with 25 stations, and HD services grew from 2 HD centers in 2010 to 20 centers all across Senegal. In 2004, the first PD center was established for the management of acute and chronic kidney failure in children and adults using continuous ambulatory PD and automated PD. 48 The costs of dialysis were first fully and then partially borne by the patient until 2012. Since 2012, dialysis costs, with the exception of epoetins and laboratory tests, are fully covered by the government in the public sector and partly covered in the private sector. In the public sector, dialysis supplies are obtained through the National Pharmacy Supply, through 2-year international tenders, permitting regular renegotiations. Kidney transplantation has not yet been done in Senegal. However, a working group with the support of experts drafted texts and laws governing organ transplantation, which passed a National Assembly vote on November 27, 2015. A presidential decree establishing the National Council for Organ Transplantation is on standby.

Training and education in nephrology

A nephrology school was opened in 2005 in Dakar to fill the gap of nephrologists in the sub-Saharan Africa region as no single country had more than 5 nephrologists, half the countries had no nephrologists, and Senegal had only 3 nephrologists. Between 2005 and 2017, by combining internal medicine and nephrology, the school trained 104 nephrologists from 21 African countries in a 4-year curriculum (including 2 semesters in France). A 2-year curriculum for nephrology nurses was introduced in 2008 and has trained 90 senior nephrology nurses from 7 African countries. In collaboration with the ISN, 3 training workshops on AKI, CKD, and PD have been organized with >400 participants per workshop to meet continuing medical education goals. 49

A working group with diverse experts (doctors, biologists, surgeons, pharmacists, and administrative staff) has been set up by the MOH to achieve an integrated CDK/ESKD care strategic plan. This strategy will enhance awareness and prevention, propose ways to reduce the growing number of patients on dialysis waiting lists, and extend PD to rural areas as it costs less than HD and will allow more patients with ESKD to be treated with dialysis. The annual cost per patient is US$13,650 for PD compared with US$18,000 for HD. 50 Training standards for health care workers must be developed in conjunction with nephrologists. The National Council for Organ Transplantation will be established, and the support of foreign partners will be needed for the accreditation of the initiation of living-related kidney transplantation.

An integrated CDK/ESKD care strategic plan was developed in 2019. The number of patients with CKD on dialysis has grown from 50 in 2010 to >800 currently; this number was doubled in 2019 with the opening of 10 new HD centers across the country. Two new PD centers were opened in 2019. This expanded the treatment of 60 patients with CKD and 20 patients with AKI at the current single center to the treatment of >150 patients with CKD and 50 patients with AKI. From 3 nephrologists in 2008, the country currently has 27 nephrologists and 128 nurses with specialization in nephrology; the goal is to train 5 additional nephrologists and 10 additional specialized nurses per year. The establishment of the National Council for Organ Transplantation will set the rules and criteria for accreditation, enabling the first successful kidney transplantation in Senegal in 2019.

CKD Strategy Cases

Uruguay (high-income country): prevention and treatment of ckd.

Uruguay, a developing country in South America with 3.44 million inhabitants, was classified as a non–Organisation for Economic Co-operation and Development high-income country by the World Bank in the last decade. In recent years, there has been a sustained growth in the aging of the population, and life expectancy at birth has increased to 77 years (73 years for men and 81 years for women). A National Integrated Health System (SNIS in Spanish) was launched in 2008 to provide UHC to the entire population. The total expenditure on health per capita in 2016 was ∼US$1800, which represents 8.6% of the nation’s gross domestic product. 51

The SNIS is funded by contributions from employers, employees, retirees, and tax revenues that go to the National Health Fund (FONASA in Spanish) and the National Fund of Resources (FNR in Spanish) ( Figure 3 ). 52 The FNR is a public nongovernmental agency, created by law in 1980 with the purpose of providing funds for highly specialized medical procedures, such as dialysis and transplantation, on the basis of approved protocols. This fund accounts for ∼10% of all public expenditures on health; expenses related to dialysis account for ∼27% of the entire fund.

National Integrated Health System (SNIS in Spanish) financial sources in Uruguay. Reproduced with permission from Ministerio de Salud Pública. La Construcción del Sistema Nacional Integrado de Salud. 2005–2009. Available at: http://www.paho.org/hq/dmdocuments/2010/construccion_sist_nac_integrado_salud_2005-2009-uruguay.pdf . Accessed March 18, 2018. 52

Action and strategies for CKD/ESKD care

UHC of patients receiving KRT has been available since 1981, with the financial support of the FNR. Data on these patients are collected by the Uruguayan Dialysis Registry.

In April 2004, representatives from the Uruguayan and Latin-American societies of nephrology, the Uruguayan Department of Health, and the FNR signed the Declaration of Montevideo with the aim of enhancing CKD care and recommended an Advisory Committee on Renal Healthcare to develop a National Renal Healthcare Program. Six months later, a pilot program was launched that included (i) education programs on kidney health care, including information on a healthy lifestyle, in the general population, with the aim to reduce cardiovascular and kidney risk factors; (ii) increased accessibility to kidney health care at the primary care level; (iii) promotion of early diagnosis of CKD in the population at risk; (iv) enhanced care given to patients at all stages of CKD; and (v) prevention of cardiovascular morbidity and mortality, as they are high in the target population. 53 , 54

The methodology for developing and spreading the National Renal Healthcare Program included several advances: (i) the development of clinical guidelines for identification, 55 evaluation, and management of patients with CKD at the primary care level; (ii) the creation of kidney care teams (including a nephrologist, a dietitian, and a nurse) to work in primary care centers to treat patients referred to them by primary care practitioners; (iii) the management of patients with CKD stage 1 to 3 directly by the laboratory; and (iv) patients with CKD stage 4 and 5 were referred to a CKD advanced clinic, staffed by a formal multidisciplinary team including nephrologists, dietitians, nurses, psychiatrists, vascular surgeons, and social workers.

An online CKD registry housed at the FNR records data on patients with estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m 2 and persistent albuminuria >300 mg/d (or >30 mg/d in patients with diabetes) and features a centralized alarm system to minimize failure to follow-up. 56 Although the National Renal Healthcare Program is not mandatory for every health care provider, the feasibility of this is being studied. 57

Since 2009, testing for CKD in high-risk populations (case finding) has been incorporated into the mandatory health checkups of the working population via a decree of the Department of Health. Evaluation includes urine examination and serum creatinine tests in diabetic and hypertensive individuals. 58

Not all Latin American countries provide the same level of CKD care, which is why the Latin-American Society of Nephrology and Hypertension (SLANH in Spanish) and the Pan American Health Organization declared that all countries should improve CKD care and increase coverage of dialysis treatment. Together, through Pan American Health Organization’s virtual space, they launched an online course (in Spanish and Portuguese) on CKD prevention and care in July 2016, aimed at primary care practitioners throughout Latin America. 59

Uruguayan Dialysis Registry

Data from the Uruguayan Dialysis Registry found that diabetic and hypertensive diseases are the most common causes of ESKD. 60 The prevalence of ESKD was 756 patients pmp, with 90% on HD and 10% on PD in December 2014; the prevalence of ESKD is 1031 pmp when patients with a functioning kidney allograft are included.

CKD registry

The target population and the variables included in the registry have already been described elsewhere. 61 Between October 1 and December 31, 2017, 20,879 patients were recorded; the mean age was 66 years, and 47.6% were female. The most frequent causes of CKD were vascular nephropathy (40.8%), diabetic nephropathy (19.1%), obstructive nephropathy (7.9%), and primary glomerulonephritis (4.8%). The most frequent risk factors for kidney disease were hypertension (86.9%), dyslipidemia (54.2%), diabetes (37.3%), and obesity (37.7%). Most patients were referred to a nephrologist at later stages (CKD stage 3 or greater). 62

Every year, the Advisory Committee on Renal Healthcare carries out an evaluation that assesses the quality of care at the primary level, the achievement of therapeutic goals under nephrology care, the rate of progression of CKD, and the mortality due to ESKD. There has been a sustained increase in blood pressure control care since 2005, with the proportion of patients with systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg rising from 36.5% to 63.9% and from 58.5% to 86.5%, respectively. 63

Table 3 highlights some indicators of kidney care in Uruguay. 64 More than 50% of patients are stabilized with an eGFR loss of <1 ml/min per 1.73 m 2 per year, and 79% of patients with diabetes and albuminuria are taking renin-angiotensin system blockade (despite heterogeneity between groups, ranging from 54% to 96%). The risk of new cardiovascular events was related to previous cardiovascular disease, diabetes, male sex, and increased age and albuminuria and had a U-shaped curve for systolic blood pressure. 65 Other than well-known risk factors such as albuminuria and blood pressure, acidosis was related to greater increase in creatinine. 66 Finally, there is evidence that predialysis CKD care may improve outcomes once patients are established on dialysis in Uruguay. 67

Table 3

Achievement of quality of care indicators under nephrology care in Uruguay (National Renal Healthcare Program 2004–2016)

eGFR, estimated glomerular filtration rate; LDL, low-density lipoprotein; RAS, renin-angiotensin system.

Since 1981 in Uruguay, there is UHC for dialysis. A CKD screening and prevention program was launched in 2004. Today, these are being incorporated into mandatory health programs, with the aim of making them universal throughout the country. There has been improvement in the quality of care as well as a reduction in CKD progression; the potential benefits of predialysis CKD care seem to extend even to patients who eventually have kidney failure. CKD care requires the commitment of the nephrology community and the national authorities. The former provides guidelines for systematic CKD detection and follow-up, while the latter sets the framework for health care providers and ensures the provision of UHC for treatment from the early stages of CKD to dialysis and kidney transplantation.

Thailand (upper-middle-income country): unique CKD prevention program

The prevalence of CKD stage 3 and 4 in Thailand is 9.3% for those older than 18 years, representing 4.8 million people, with a further 4.6 million people with CKD stage 1 and 2. 68 Diabetes mellitus and hypertension are the main causes of CKD. 69 The Ministry of Public Health has divided the country into 12 health care regions (excluding the Bangkok metropolitan area), with each region consisting of 4 to 8 provinces covering a population of ∼5 million. Within each province, there are between 6 and 30 districts, each with their own district hospital. Within each district, there are a further 5 to 10 subdistrict health offices. A district hospital usually comprises general practitioners, nurses, pharmacists, a physical therapist, and, in larger hospitals, a nutritionist. At each subdistrict health office, there are 1 to 2 public health officers and 1 to 2 community nurses, caring for anywhere between 3000 and 5000 inhabitants. Community nurses are responsible for basic drug prescription, on behalf of the district hospital, and for treating common ailments. Moreover, there are village health volunteers, grassroots personnel, who provide a connection between villagers and health personnel and cover public health issues at the village level. Basic health care programs in Thailand are implemented through this infrastructure. Across Thailand, there are ∼10,000 subdistrict health offices and >1 million village health volunteers. 70

Diabetes mellitus and hypertension are the 2 most common NCDs in rural areas. To cope with these problems, general practitioners, diabetes/hypertension case manager nurses, and multidisciplinary care teams work together at the district hospital level. Community nurses and village health volunteers are also responsible for medication refills for stable patients and facilitate patients’ self-care and any necessary lifestyle modifications. Key performance indicators from all public hospitals are transferred to the Health Data Center of the Ministry of Public Health. Table 4 illustrates a set of key performance indicators of diabetes and hypertension. 71

Table 4

Key performance indicators of diabetes mellitus and hypertension reportable to the Ministry of Public Health, Thailand

HbA 1c , hemoglobin A 1c .

It is challenging to use the limited resources available in the country to delay the progression of CKD on a national scale. Community nurses and village health volunteers, who are more present in the community, can be trained to decrease the reliance on multidisciplinary care teams who are present only in hospitals. This is a paradigm shift from hospital-based to a joint hospital-community–based approach.

To test this concept of care, a pilot project was launched a few years ago in Kamphaeng Phet Province, 400 km north of Bangkok. In brief, this study took place at 2 districts within the province. 72 In district hospital A (control), there was no multidisciplinary care team available and patients were cared for as usual by general practitioners and diabetes/hypertension/NCD nurses. There were no home visits by community nurses/village health volunteers. In district hospital B (intervention), multidisciplinary care teams, community nurses, and village health volunteers were trained on CKD with information on lifestyle modifications and dietary counseling. Educational materials and a protocol checklist were provided in accordance with the Nephrology Society of Thailand and international guidelines on CKD management. 73 , 74 CKD cases were referred by community nurses/village health volunteers during regular home visits to multidisciplinary care teams at the district hospital. The community nurses/village health volunteers also had a checklist on exercise, smoking cessation, avoidance of analgesic/nonsteroidal anti-inflammatory drugs, and avoidance of high salt and protein intake. Two years later, patients with CKD in the intervention group had lower dietary salt and protein intake and lower rates of eGFR decline than did those in the control group. 75 An economic evaluation demonstrated that this program was cost-effective. 76 The conclusions of this study imply that integrated care provided by multidisciplinary care teams at district hospitals in combination with home visits by community nurses/village health volunteers could help delay the progression of CKD through lifestyle modifications, without the intervention of specialists.

In 2015, the Ministry of Public Health announced the prevention of CKD as a national health priority. All referral, provincial, and district hospitals were requested to set up multidisciplinary care teams around CKD. A protocol checklist on the essential parts of CKD management and key performance indicators of CKD were agreed upon. A reference eGFR equation was declared, and the implementation of national serum creatinine standardization is underway.

Our findings illustrate favorable outcomes in a CKD prevention program at a national scale ( Table 5 ). 71 It is yet too early to identify absolute eGFR change over time. We recognize that the key success factors behind our CKD program are the homogeneity of an existing well-organized primary health care system, the inclusion of an integrated care team at district hospitals, frequent home visits by community nurses and village health volunteers in the program, and, most importantly, a strong sense of belonging to their native homeland of the personnel. Our experience shows that in developing countries such as Thailand, combating CKD progression under limited resources is possible, provided that an integrated care program is developed, including trained multidisciplinary care teams, educational materials, protocol checklists, and dedicated community nurses and village health volunteers. This program could be sustainable and cost-effective.

Table 5

Key performance indicators of CKD reportable to the Ministry of Public Health, Thailand

ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blockade; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HbA 1c , hemoglobin A 1c .

United Arab Emirates (high-income country): early detection of CKD in Abu Dhabi

In 2012, the prevalence of ESKD and CKD in Abu Dhabi were unknown, but the population on dialysis was doubling approximately every 5 years. Of the new patients starting dialysis, 90% started with <90 days of predialysis care, only 2% of patients had a fistula at their first dialysis session, and patients primarily started on HD. There were no systematic attempts at early detection and management of CKD as the projection of future patients with CKD was unknown.

SEHA, the government health system within Abu Dhabi, has a single electronic medical record system that covers the whole country. The data contain patient demographics and information on all patient encounters. Between September 2011 and October 2012, data on 212,314 adults were extracted from the electronic medical record. The eGFR was calculated for every serum creatinine measurement and was used to calculate an estimate of CKD prevalence on the basis of the population breakdown. The prevalence of CKD stage 2 to 5 was estimated to be 22.6% in Emirati men, 12.9% in Emirati women, 26.6% in foreign men, and 16.5% in foreign women.

To address the relative high rates of CKD, extensive discussions occurred at both primary and secondary levels of care; a potential solution was introduced in February 2014. This solution included the adoption of several strategies: the automated calculation of eGFR using the CKD Epidemiology Collaboration 77 equation embedded within the electronic medical record; an automated addition of International Classification of Diseases 9th and 10th Revisions codes for CKD to the electronic medical record based on Kidney Disease: Improving Global Outcomes (KDIGO) CKD 2012 criteria 74 ; an algorithm-based management of CKD; online physician decision support for referral and medication management; physician feedback at the individual, practice, and regional level; and kidney nurses working both at the primary level of care and in multidisciplinary advanced CKD clinics.

At the outset of the program, 35% of patients with CKD stage 3 to 5 managed within primary care and 20% managed within secondary care were taking nonsteroidal anti-inflammatory drugs. From 2011 to 2012, these rates fell to 15% and 10%, respectively. To date, 29,000 patients with CKD have been identified, of whom 25% are at high risk of progression as per the KDIGO classification. 74 More than 3500 patients, however, have had a >30% improvement in eGFR over a 2-year follow-up period. The presentation rate for dialysis with <90 days of predialysis care (emergency start) has fallen from 90% to 35%. The proportion of patients commencing dialysis with an arteriovenous fistula has risen each year, with 34% starting dialysis with a fistula in 2018.

This program of early detection and management of CKD has been extremely successful and continues to improve outcomes for Emirati patients. The program has clearly demonstrated the ability to modify physician prescribing behavior and exemplifies value-based health care with improved patient outcomes at a reduced cost to the health system. Data analysis is ongoing, with more work needed on defining the incidence density of progression to KRT and death as well as hazard ratios of progression and the impact of changes in medication regimen.

HD Strategy Cases

Malaysia (upper-middle-income country): near-universal coverage for dialysis.

Nephrology services in Malaysia have come a long way, from a humble beginning in the 1960s with steady growth to the mid-1970s, when the country was still categorized as an agricultural-based LMIC. With rapid development in the last 2 decades, a full range of nephrology services is now readily available throughout the country at an affordable cost. For an upper-middle-income country, Malaysia has an impressive treatment rate for patients with ESKD.

Action and strategies for HD and PD

How does malaysia achieve near-uhc for dialysis.

Over the last 5 decades, the nephrology community in Malaysia has worked toward achieving the World Health Organization indicators of UHC 78 of dialysis via good stewardship and governance (provided by the government), nephrology champions, key opinion leaders, and professional societies via the following strategies.

Effective stewardship of health reforms

• • Strong support via the MOH by providing sufficient funding for the development, operation, and subsidy of dialysis centers and services throughout the country.
• • Ongoing planning over the last 40 years.
• • Cooperation between private corporations and NGOs to develop more HD centers.

Effective stewardship of public funds

• • Allocation of more funds from the MOH to expand services, particularly in rural areas.
• • Allocation of subsidies to NGOs by the MOH and Treasury.
• • Outsourcing of dialysis to private centers by the Public Service Department, Social Security Organization, and zakat. All of the above agreed to consider dialysis as rehabilitation therapy.
• • Purchasing HD services from all qualified providers.

These measures were a major departure of standard policies of the public sector in the 1970s and 1980s. The funding of dialysis was one of the very first mixed public, private, and NGO financing operations in Malaysia.

Stewardship in proper training of doctors and allied health staff

• • Emphasizing the importance of a proper training program for nephrologists, kidney nurses, and allied head staff, with a syllabus, logbook, and exit evaluation where trainees are assessed by local and external examiners.

Ensuring quality and integrity

• • Introduced quality initiative efforts, such as the development of practice guidelines on KRT and a document on Hemodialysis Quality Standards.
• • Established National Renal Registry (jointly between the MOH and the Malaysian Society of Nephrology) to provide accurate data for health care planners, clinicians, and multinational dialysis industry companies.

Public–private partnership

• • There continues to be collaboration among government, professional societies, private industry, NGOs, and local manufacturers (consumables and solution). There is also widespread implementation of health care laws that have enabled organizations to start an HD facility irrespective of whether they have links to a hospital.

During the last 3 decades of transformation from LMIC to upper-middle-income country, the above measures have resulted in near-universal access to dialysis for all patients with ESKD, at a reasonable cost, with comparable quality to many developed countries.

Malaysia has an interesting dual-tiered system of health care services consisting of a government-led public sector that coexists alongside a private-NGO sector, creating a synergistic public–private/NGO model. The government is the main source of funding for new and existing patients on dialysis (55%–60%); out-of-pocket payments or self-funding for dialysis was ∼26% to 30%; and funding from NGOs remained at 11% to 15% over the years. 78 Public financing, mainly through taxation and/or social health insurance (e.g., Social Security Organization), is the dominant form of financing for dialysis. The majority of patients on HD are treated in the private/NGO sector (54%), but almost all patients on PD are treated in government facilities (97%) via financing operations described above. 79 The total health expenditure in Malaysia was 4.21% of the gross domestic product (RM51,742 million) in 2016 80 ; the total spending on dialysis was US$100 million, accounted for 1.72% of the total health expenditure in 2005. 81

In Malaysia, diabetes and hypertension were the most common causes of ESKD, 82 with the prevalence of 17.5% and 30.3%, respectively, in those older than 18 years. 83 The prevalence of CKD stage 5 was 0.36% in those older than 18 years. 84 Recent forecasting estimates that the cost to treat 51,269 patients on dialysis in the year 2020 will be US$384.5 million. 85 This burden has implications for future health care financing. The prevalence of ESKD is increasing at an alarming rate. Options proposed to tackle this issue include early medical intervention to slow the progression of CKD in high-risk patients, the promotion of kidney transplantation, and the use of more cost-effective dialysis therapies. In Malaysia, kidney failure prevention initiatives have been carried out nationwide, including patient screening in the primary care setting, the prevention of kidney failure workshops targeting primary care doctors and allied health care staff, the development of clinical practice guidelines on CKD management and nephrology services operational policy, and national public awareness of World Kidney Day. Despite kidney transplantation providing the best KRT option, the transplantation rate remains low at 3 pmp owing to a lack of donors, leaving the choice of KRT between HD and PD. 82

In Malaysia, citizens can access the subsidized dialysis services provided by the MOH at university hospitals, Ministry of Defense hospitals, and local authorities. Public sector health care services are considered a national health service with its tax-based financing and heavy subsidies. NGOs and political parties also provide support either by providing services (e.g., dialysis services by the National Kidney Foundation), subsidizing part of the payment, or assisting in the appeal for public donations. These measures combined have resulted in expanded coverage of stand-alone dialysis services over the years ( Figure 4 ), with the number of dialysis centers across Malaysia increasing from 205 in 2000 to 758 in 2014. 79 , 81 , 86

Providing dialysis to meet Malaysian needs. Dialysis treatment by sector (per million population [pmp]), 1980–2016. 79 , 81 , 86 BAKTI, Badan Amal dan Kebajikan Tenaga Isteri-Isteri Menteri dan Timbalan Menteri (Charitable and welfare bodies of the wives of Ministers and deputy Ministers); HD, hemodialysis; JPA, Jabatan Perkhidmatan Awam (Public Service Department) (civil servants and their dependants would be reimbursed by the government); MOH, Ministry of Health, Malaysia (public health care services are funded through general taxation, with annual health budgets allocated by the Ministry of Finance to the MOH); NGO, nongovernmental organization (NGOs are providing support to access dialysis by either providing some of these services [e.g., dialysis services by the National Kidney Foundation {NKF}], subsidizing part of the payment, or assisting in appealing for public donations [e.g., NKF]); SOCSO, Social Security Organization (a government-run social insurance body that receives mandatory contributions from private-sector employees earning below US$950 per month); YKN, Yayasan Kebajikan Negara; Zakat, state-run Islamic social welfare organizations reimburse eligible patients for certain treatments and dialysis, which was included as a rehabilitation therapy.

Between 2005 and 2014, private dialysis centers have almost tripled from 6 to 14 pmp, NGO centers increased from 4 to 5 pmp, and the pmp rate of public centers remained unchanged. Private dialysis centers are distributed mainly in economically developed west coast states of Peninsular Malaysia. The government operates most of the dialysis centers in less developed areas.

Reimbursement by government agencies per HD treatment at private and private for-profit HD centers has not changed since 1999 and remains at about RM120 to RM200 and at RM150 to RM200 per dialysis session, respectively. 81 There were 37,183 patients on dialysis in 2015. 79 In 2015, the incidence and prevalence rates of dialysis were 261 and 1295 pmp, respectively. 82 These rates compare favorably to more developed countries in the region, such as Singapore, South Korea, and Hong Kong. 87

In summary, the number of patients receiving KRT has increased sharply over the last few decades. Malaysia, an upper-middle-income country, has been able to achieve near-UHC for dialysis and consistently reports outcomes; this is usually observed only in industrialized nations. This achievement is due to good stewardship and governance shown by the government, professional societies, NGOs, and clinical champions.

Malawi (low-income country): unique strategy for ESKD care

Malawi, a country of 16.7 million people, has offered free HD services for both AKI and ESKD since 1998. 88 , 89 The first dialysis unit was established in 1998 in Lilongwe with a donation of 4 Gambo AK 95 machines (Baxter International Inc.; Deerfield, IL). As the original HD machines were in poor working order, with spare parts difficult to obtain, patient care was often interrupted and outcomes were generally poor. A second unit was established in Blantyre in 2011 with 4 of the same HD machines to face the increasing demand for services and to reduce the large distances that patients would be required to travel to access dialysis.

All HD machines and water plants were replaced at both units between 2013 and 2014. Lilongwe now has 10 stations and Blantyre has 5. A public–private initiative with Fresenius Medical Care (based in South Africa) has provided 5 additional units; the water plant and dialysis machines were offered at no direct capital cost as part of a 5-year contract to purchase consumables from Fresenius. Training of medical and nursing staff has also been a core component of improved service delivery in Blantyre through the Sister Renal Center Program from the ISN. Dialysis is provided on a twice weekly basis, which has increased the number of patients treated, though at a cost of delivering a lower dialysis dose.

Although HD services have expanded, providing integrated care for kidney disease remains a challenge. Regular adult and pediatric nephrology clinics help identify patients approaching ESKD, but the overwhelming majority of patients present in extremis, requiring emergency dialysis for both AKI and ESKD. Screening patients for CKD in high-risk groups such as those with diabetes, hypertension, and HIV remain challenging because of many reasons including the cost of materials such as urine dipstick and laboratory reagents, a low awareness of kidney disease among the public and medical professionals, and the sheer volume of patients.

There is currently no access to transplantation within Malawi; instead, patients are sent overseas for living donor transplants at a cost of ∼$30,000 borne by either the patient or the government. PD has been delivered when suitable supplies of PD fluid and equipment have been available, but these periods are brief and difficult to sustain. Thus, HD remains, and is likely to remain, the predominant dialysis modality in Malawi. Vascular access for HD also remains a challenge, and surgical expertise is urgently required to address this. Some patients do have a native arteriovenous fistula that was created by either a surgeon in Malawi or visiting specialists, but a regular vascular access service has not formally been established. Complications from both temporary and semipermanent HD catheters are both common and severe.

Significant efforts are being made to provide integrated care for CKD and AKI in Malawi. Both HD units have focused on the development of predialysis nephrology services in terms of clinical activity, teaching, and research. Screening for CKD in high-risk patients such as those with diabetes and HIV has identified an unexpectedly high prevalence of CKD; this further highlights the importance of robust mechanisms for the early detection and management of CKD. 90 , 91 Clinical expertise for nephrology in Malawi remains a significant challenge—the country has just received its first qualified nephrologist. The nursing staff in dialysis units represents an excellent source of clinical expertise and have been instrumental in advancing the delivery of dialysis care and education together with physicians and clinical officers.

Kidney services in Malawi have been supported by bidirectional teaching and training programs with Barts Health NHS Trust in the United Kingdom. This partnership has helped develop clinical, research, and teaching expertise. The volume of patients with kidney disease in Malawi, both acute and chronic, has required the development of a specialist kidney ward to care for patients with both AKI and ESKD at Queen Elizabeth Central Hospital in Blantyre. To address the needs of patients who do not proceed with dialysis, a partnership with palliative care services has been established. This service provides holistic and symptomatic care for patients with ESKD in the absence of dialysis. 92 , 93

Preliminary discussions around providing transplantation in Malawi have identified attendant laboratory, pharmacy, clinical, legal, and ethical challenges; although difficult, they are not impossible to overcome. Although transplantation in Malawi will ultimately lead to a better quality of life for patients and lower direct cost to the government, it remains some years away.

The total number of patients on dialysis in Malawi has dramatically increased with the provision of new equipment, allowing better access to dialysis for both patients with ESKD and those with AKI. 88 Increasing dialysis has saved lives but at a high cost to the health economy, and the HD capacity is not yet sufficient to treat every case of ESKD. Patient dialysis groups in Malawi have become strong and vocal advocates for services for patients with kidney disease and are instrumental in sustaining and improving HD services in conjunction with clinicians. The educational activities undertaken over the last 7 years have strengthened the clinical and research expertise in Malawi. There are significant challenges ahead for kidney care in Malawi, but working with the ISN on the Kidney Care Network project has the potential to make a major impact on the care of AKI, ultimately saving lives. Strengthening the breadth and depth of clinical nephrology expertise sustainably will require continued financial and operational support from the Malawi government and is essential to a national kidney strategy in Malawi.

Kenya (lower-middle-income country): upscaling HD

Kenya, with a population of >50 million, has a huge number of patients with kidney failure and who would potentially benefit from KRT.

HD was first offered in Kenya in 1964 when an HD machine had to be flown in from England along with a team of doctors for a British soldier. In 1970, regular HD was offered in an intensive care unit at the referral hospital, Kenyatta National Hospital (KNH) in the capital Nairobi. PD was introduced in 1971, but this expertise was available only in Nairobi. A kidney unit was established at KNH in 1979, and it remained the only unit in the country until 1982, when private hospitals started offering both HD and PD. As these units were located only in Nairobi, other regions still had no access to HD and anybody who needed dialysis traveled to the capital city. By 1990, most provincial hospitals had the personnel to provide acute PD and a few patients started on continuous ambulatory PD. With the introduction of the double bag system in 2002, PD slowly became costlier than HD and few patients opted for this modality. Starting in 2002, satellite HD units appeared outside Nairobi; by 2006, however, there were still only 4 government hospitals offering HD across the country.

In 1978, the first ever kidney transplantation was carried out in a patient whose horseshoe kidneys had been mistaken for an abdominal mass and inadvertently removed; she lived for 1 year after surgery. A few private hospitals started kidney transplantation in 1984, though the numbers were low and irregular. By 1988, KNH was also doing kidney transplantation; however, over the next 20 years, only 130 had been done.

In 2010, it became clear that the government could no longer cope with the growing burden of ESKD and the Kenya Renal Association drafted a plan to increase kidney services ( Table 6 94 , 95 , 96 , 97 , 98 , 99 ).

Table 6

Progress of kidney services in Kenya since 1995

Actions and strategies for CKD/ESKD care

A partnership between KNH and Novartis Pharmaceuticals was established in 2010 to retrain the transplantation team at KNH. Over the next few years, with travel between Spain and Kenya, the team was fully equipped to run a successful transplantation program. The number of transplantations increased, and expertise was shared with some of the private hospitals.

Because of lobbying from powerful dialysis patient groups to improve the situation in the country, the government implemented the Kenya Renal Association recommendations to increase kidney services in 2015. Recommendations that were implemented included the establishment of at least 1 HD unit in each of the 47 counties with 5 machines each over a 2-year period. This task involved the government creating new structures in regions that did not have the necessary infrastructure. Currently, 90% of the county units, representing 40% of dialysis units in the country, are in place and delivering services to patients.

The National Hospital Insurance Fund, established in 1966, provides UHC to all Kenyans 18 years or older and who have a monthly income of >US$10; monthly contributions range from US$5 to US$17. The National Hospital Insurance Fund has the aim of ensuring access to affordable, sustainable, equitable, and quality care and was entrusted by the government to provide funds to reimburse dialysis centers.

Kenya has been entrusted with the East African Kidney Institute of Urology, Nephrology, and Transplantation as part of a new initiative set up by the African Development Bank. The overall objective of this institute is to develop a world class institution that facilitates the realization of the vision to strengthen health training, research capacity, and provision of services to the local and international communities, more so in the East and Central African regions. Although a full nephrology fellowship program is 2 years in length, to address the urgent need for trained doctors, the institute created a 3-month preceptorship.

Despite the advancements in infrastructure, many challenges remain ( Table 7 ). A good supportive structure is needed to ensure the success of the program. Involving partners such as the World Health Organization, United Nations, and ISN to support the program and endorse safety is important. Adapting good guidelines that suit the patient needs is critical.

Table 7

Challenges for the growing kidney replacement therapy program in Kenya

BMD, bone mineral density; PD, peritoneal dialysis.

The MOH is charged with implementing this program and to ensure standards are met by empowering the medical board. Funding comes from the National Hospital Insurance Fund, and the supply of medicines comes from the Kenya Medical Supplies Authority, a state corporation whose mandate is to procure, warehouse, and distribute drugs and medical supplies for prescribed public health programs.

In 2017, a health bill was passed into law, which enables public hospitals in Kenya to start deceased donor (DD) kidney transplantation. Once implemented, this law will ease the number of patients waiting for a kidney transplantation. The Kenya Renal Association, which oversees the program, has started creating a registry for dialysis and transplantation. Nephrologists work closely with the MOH to ensure standards for safe HD are met by each unit. A national epidemiological survey to determine the number of patients with kidney disease in Kenya is being planned. Despite all these systems being put into place, further team efforts are required to ensure success.

PD Strategy Cases

South africa (upper-middle-income country): pediatric pd for eskd.

ESKD in pediatric patients is a significant problem in South Africa as it is in many parts of the world. Adults often get preference in terms of dialysis and transplantation.

Facilities are present in 3 of the larger academic centers—Johannesburg, Durban, and Cape Town—to provide KRT and transplantation to children who have access to these centers. There is lobbying at the local hospital level for the purchase of pediatric and, in some centers, infant dialysis equipment. Provision for pediatric facilities has also been facilitated in some private facilities. There has been some lobbying at the government level for specific pediatric support but with limited success.

Like adult centers in South Africa, pediatric centers do not provide chronic dialysis for children unless they are suitable for transplantation. This has proved difficult as many children have started on acute dialysis, only to be changed to conservative care as their family and home facilities are not suitable for long-term dialysis. This transition plan has been difficult for some centers, and thus long-term dialysis has been started in some children without a satisfactory plan for future dialysis.

The first strategy in developing a pediatric dialysis program in South Africa is to create pediatric programs where adult programs exist. Adult programs can then provide the initial knowledge and technical support associated with caring for adolescents and bigger children.

The next strategy is to use a PD-First approach for children who have been accepted for transplantation and thus dialysis. This uses automated home cycle machines for overnight dialysis while children are sleeping, enabling them to continue school during the day. Families are trained during an in-patient visit over a period of 2 weeks and then examined on their technique before discharge. In most centers, a single home visit is done to see if this is a suitable option as well as to advise them in practical matters of having a dialysis machine at home. There are currently 2 marketed machines for home automated PD in children: Homechoice Claria by Baxter International Inc. and Sleepsafe by Fresenius Medical Care (Waltham, MA).

Advanced technology (Claria Baxter) now allows the remote daily follow-up of overnight dialysis patterns.

Other strategies include the training and employment of specialized advanced nurse practitioners who can operate in- and outpatient PD programs.

Children who have failed PD and would go onto HD provide the challenge to appropriate pediatric and infant HD lines and filters. While pediatric centers are being established, bigger children will often initially dialyze in adult facilities. This emphasizes the need for training of medical and nursing staff in both adult and pediatric centers.

The ultimate goal in pediatrics is to arrange kidney transplantation as soon as possible; this avoids stunting due to long-term dialysis. To ensure the success of a pediatric transplantation program, it is critical to have a few dedicated centralized areas across the country. This will centralize the skills base and improve results.

Over the last 10 years, pediatric nephrology has grown in South Africa from 10 to 27 active pediatric nephrologists. Over the last 15 years, at the Red Cross Children’s Hospital alone, we have trained a further 24 pediatric nephrologists from elsewhere in Africa.

The challenge remains to increase the training of nurses, technicians, and advanced nurse practitioners to provide dialysis and transplantation for children.

Overall, the situation is slowly improving: in December 2016, the South African Renal Registry found that there were 54, 53, and 86 patients younger than 19 years on PD and HD, and with a functioning transplanted kidney, respectively (with permission from Razeen Davids, Webmaster of South African Renal Registry). The result of staff training as well as collaboration with adult nephrology teams gives hope for the future of pediatric patients with nephrology disorders in South Africa as well as in other parts of Africa.

Transplantation Strategy Cases

South korea (high-income country): system development for dd kidney transplantation.

Kidney transplantation improves the quality of life of patients with ESKD and is cost-effective. The first living-donor kidney transplantation in Korea was conducted in 1969, and the first DD kidney transplantation was conducted in 1976. The number of hospitals performing kidney transplantation has since rapidly increased. However, as most kidneys are donated within families and there is an increasing trend of smaller families, living donor kidney donation has stagnated. Furthermore, the revered traditional Confucian view teaches that your entire body was given to you by your parents and people are taught to value their bodies. The meaning of this teaching has been overinterpreted to mean value all parts of human body even after death , resulting in the rejection of organ procurement from DDs.

To address the shortage, in 1988, the Korean Society for Transplantation proposed DD organ transplantation legislation to the congress. Although DD kidney transplantation was being conducted by several hospitals at the time, it took 10 years to secure legal support for it. This situation resulted in kidneys from the poor being traded on the black market. Thus, a renewed legal review of brain death was initiated, and the Organ Transplantation Law was passed in 1999 and the Korean Network for Organ Sharing was established in 2000. The major role of the Korean Network for Organ Sharing was to review the legal and ethical relationship between living donors and their recipients. It also became responsible for the management of the transplantation wait-list and the allocation of DDs. Over time, the Korean Network for Organ Sharing became a national authority, regulating organ transplantation–related activities.

The overly tight regulation of each process soon resulted in a decline in kidney transplantation, and the annual number of patients who died while waiting for organ transplantation increased. Patients became increasingly desperate, and overseas transplantation rapidly increased starting in 2002. The Organ Allocation Study Group, under the Korean Society for Transplantation, elected to change its name to the Deceased Organ Donation Improvement Program Committee in 2009 and started devoting its efforts to formulating strategic plans for reactivating DD organ transplantation. The Organ Allocation Study Group cooperated with the congress in revising the existing law in 2010, adding a law on mandatory reporting, the establishment of an independent organ procurement organization, and the implementation of a transplantation registry.

Vitallink is an NGO that was established by the Korean Society for Transplantation in August 2009 to promote public awareness of DD organ donation. Vitallink educates medical and high school students about organ donation. Vitallink also established the Korean Organ Donation Network in 2010 to conduct consistent education for NGO leaders. They jointly collaborate with Catholic and Buddhist NGOs to host various campaigns. Finally, Vitallink has been supporting the development of the Asian organ transplantation program through annual workshops and the provision of training courses for medical professionals from Korea and abroad.

The Korea Organ Donation Agency was established in 2009. Currently, this agency has jurisdiction over 3 regional divisions. The main responsibility of procurement coordinators is to discover potential DDs by visiting hospitals. When the Korea Organ Donation Agency receives notification of a potential brain death donor, they first visit the hospital to conduct a primary medical evaluation for donor eligibility and then obtain consent from the family, process the evaluation of brain death, and contact and coordinate the organ procurement teams and operations. After donation, they collect the body to transfer to the family and provide emotional support. The Korea Organ Donation Agency is also in charge of education for medical professionals and donor families.

In 2014, the Korean Society for Transplantation established a web-based registry, the Korean Organ Transplantation Registry. The Korean Organ Transplantation Registry collects data on ∼85% of all organ transplantation and issues an annual report. They have hosted various seminars and provide research grants and awards. The Korean Organ Transplantation Registry has now started the Asian Organ Transplantation Registry (ASTREG).

The rate of DD organ transplantation in Korea has greatly increased because of the adoption of new strategies ( Figure 5 ). 100 This increase has led to a decrease in the number of overseas transplantation ( Figure 6 ). 100 As of 2017, the number of DD organ donations in Korea was 10.7 pmp, the highest in Asia; however, Korea is still ranked only 37th worldwide. To provide a better life for patients with ESKD in Korea, partnerships will be required with other Asian countries in organ transplantation.

Number of kidney transplantation cases in South Korea. Data from Ahn HJ, Kim HW, Han M, et al. Changing patterns of foreigner transplants in Korea and overseas organ transplants among Koreans. Transplantation. 2018;102:310–317. 100 Copyright © 2018 Wolters Kluwer Health, Inc.

Relationship between the number of overseas organ transplantation cases and the number of deceased organ donors in South Korea. Doha: Doha, Qatar; DOI, Declaration of Istanbul; IOPO, independent organ procurement organization; KODA, Korea Organ Donation Agency; KOTRY, Korean Organ Transplantation Registry. Reproduced with permission from Ahn HJ, Kim HW, Han M, et al. Changing patterns of foreigner transplants in Korea and overseas organ transplants among Koreans. Transplantation. 2018;102:310–317. 100 Copyright © 2018 Wolters Kluwer Health, Inc.

Ghana (lower-middle-income country): framework for the development of living donor kidney donation

In 2008, a living donor kidney transplantation program was established in Ghana in collaboration with the Transplant Links Community and the Queen Elizabeth Hospital Birmingham, part of University Hospitals Birmingham NHS Foundation Trust–ISN Sister Renal Center. Our model for developing a kidney transplant program involved 3 stages ( Figure 7 ): the pre-transplant stage, crucial in ensuring effective planning and long-term sustainability; and the transplant and post-transplant stages, important for clinical capacity building, patient care, monitoring, and evaluation, which then feed back into the pre-transplant stage to optimize the transplantation process.

Model for kidney transplantation in Ghana. HDU, high-dependency unit; ICU, intensive care unit.

Pre-transplant planning

The decision to undertake living donor kidney donation was based on the youthfulness of patients on dialysis, the cost of HD (beyond the means of most patients), and the opportunity for an improved quality of life. First, a knowledgeable and committed champion was identified to lead, drive, and coordinate the program through effective and ongoing engagement with all stakeholders. 101

The second step involved an assessment of the capacity of the hospital to ensure that it could support kidney transplantation. A checklist was developed to assess infrastructure : personnel, policies, protocols, laboratory support, and medicine availability. This was implemented by a team including heads of departments of medicine, surgery, pharmacy, pathology, and anesthesia. The assessment of clinical capacity included identification of comprehensive protocols for both donor and recipient work-up and immunosuppressant management, including a choice of affordable generic immunosuppressants. Identified key gaps included no legal framework for organ transplantation, a lack of transplantation surgeons, and the nonavailability of protocols and some immunosuppressive drugs.

The third step was the development of a legal and ethical framework for living donor kidney donation. In the absence of a national legal framework for transplantation, hospital management and the MOH decided to adopt the Declaration of Istanbul on organ trafficking and transplant tourism as a means of ensuring best practices. 102 , 103 To work within the principles of the Declaration of Istanbul, only living-related donors were considered. In addition, a transplant ethics committee was established, guided by the UK Human Tissue Act (2004), the World Health Organization Guiding Principles on Human Cell, Tissue and Organ Transplantation, and the Declaration of Istanbul, to independently assess the transplantation process and to avoid coercion and organ trafficking. 104 , 105 , 106 The committee comprised a retired professor of surgery, a priest, a lawyer, a clinical psychologist, and a professor in public health.

The final step was financing . Given the projected costs of a transplantation program, the hospital engaged funders including the National Health Insurance Scheme and the Social Security and National Insurance Trust. The hospital also provided letters to patients to solicit funds for transplantation. The Transplant Links Community raised enough funds to cover the costs of the visiting transplantation team, volunteers who visited during their holidays. The National Kidney Foundation–Ghana raised funds to support medicines and laboratory investigations. The cost of a kidney transplantation was estimated at US$10,000 per transplantation, including pre- and post-transplantation laboratory investigations, hospital admission, both operations (donor and recipient), postoperative management, and a 3-month supply of immunosuppressive drugs. Corporate organizations sponsored transplantation patients to ensure that all patients, even those who could not afford it, were provided for, including ongoing immunosuppressants, which average US$3600 to US$4000 per year.

• (i) Development of local clinical capacity for transplantation : A multidisciplinary clinical team made up of local nephrologists, urologists, anesthetists, clinical pharmacists, and critical care nurses was created. Clinical expertise in kidney transplantation was achieved with periods of training of surgeons and physicians in South Africa and the United Kingdom through ISN fellowship awards.
• (ii) Donor and recipient selection: Recipients along with suitable living donors were selected from dialysis centers. Two local nephrologists applied standard guidelines to evaluate donor and recipient pairs. Donors and recipients were provided with counseling and educational materials on the risks and alternatives available. Materials were provided in English; however, a team of local nurses were able to counsel in the local language. After the medical evaluation, donors and recipients were further evaluated by the transplantation surgeon and the anesthetist. The ethics committee provided an independent assessment and interviewed each pair separately and together. Once the committee was satisfied that the pair were genuinely related, that the donor was not acting under any coercion, and that the Declaration of Istanbul was adhered to, written approval was given to proceed to the transplant stage. Two other nephrologists from the international team reevaluated the donor-recipient pair before surgery.
• (iii) Transplantation procedure and follow-up: The University Hospitals Birmingham NHS Foundation Trust and Transplant Links Community teams made 2 initial visits before the first transplantation and then performed the kidney transplantations on subsequent visits. These visits enabled hands-on training of local surgeons, anesthetists, nurses, and theater technicians. The Ghanaian team adopted the University Hospitals Birmingham NHS Foundation Trust protocols, with minor modifications, for patient management and follow-up pre-, intra-, and postoperation.
• (iv) Monitoring and evaluation of the program involved entering all patients into a database for ongoing follow-up: After the first set of kidney transplantations done in 2008, the donor work-up process was reevaluated and a new donor work-up sheet was designed to reduce the cost of the donor work-up ( Appendix 2 ). Outcome of the transplantation program has been good: in the first 17 transplantations done, there was 100% 1-year patient survival and 91.7% graft survival. 106

ESKD is a global problem and cuts across all sociodemographic differences and cultural context. Despite the diversity in countries discussed here, common themes emerged in the approach to reducing the burden of CKD/ESKD:

• • the importance of screening high-risk populations and multidisciplinary care in slowing the rate of progression of CKD;
• • improving access to KRT options (HD, PD, DD, and living donor transplantation) to all patients (including rural) affected by ESKD;
• • moving toward financially sustainable KRT options; and
• • the recognition of the harm of nephrotoxic drugs.

Countries have made great strides to date in recognizing the importance of and developing strategies to address CKD/ESKD across different income status ( Table 8 ). Future work needs to continue to rely on strong data collection and analysis to identify key risk factors across populations, enact strategies that delay the onset and progression of CKD, increase universal access to appropriate KRT, and use the leverage of international collaboration to strengthen systems around the world ( Figure 8 ). Capitalizing on partnerships that can limit the financial burden on LMIC should continue to be explored. A cohesive collaborative approach among experts around the globe will continue to strengthen the international nephrology community and improve outcomes for patients with CKD/ESKD.

Table 8

Featured strategies of CKD/ESKD care stratified by World Bank economic classification

CKD, chronic kidney disease; ESKD, end-stage kidney disease; KRT, kidney replacement therapy; NGO, nongovernmental organization; NSAID, nonsteroidal anti-inflammatory drug; UHC, universal health coverage.

Strengths, weaknesses, opportunities, and threats (SWOT) analysis of chronic kidney disease (CKD)/end-stage kidney disease (ESKD) strategies .

Publication of this article was supported by the International Society of Nephrology.

DCHH reports grant support from the National Health and Medical Research Council. GGG reports grant support from CloudCath and ICON Clinical Research, Ltd. BLG reports lecture fees from Baxter, Fresenius Medical Care, Sanofi, and Kwoya Kirin and grant support from Baxter and Kwoya Kirin. JD reports consulting fees from the International Society of Nephrology. All the other authors declared no competing interests.

Acknowledgments

This article emerged as an individual product of the International Society of Nephrology’s 2nd Global Kidney Health Summit held in Sharjah, United Arab Emirates, in March 2018 and portions of the material in this document have been published in the full report from the summit (Harris DCH, Davies SJ, Finkelstein FO, et al. Increasing access to integrated ESKD care as part of universal health coverage. Kidney Int. 2019;95:S1–S33 1 ). In addition to the International Society of Nephrology, support of the summit was provided through unrestricted grants from Baxter and B. Braun.

MT was supported by the David Freeze Chair in Health Services Research at the University of Calgary. The Libin Institute at the University of Calgary is the host institution for the Pan American Health Organization/World Health Organization’s Coordinating Centre in Prevention and Control of Chronic Kidney Disease.

The authors thank Drs. Hong Teck Chua, Chwee Choon Tan, and Zaki Morad for assisting with the preparation of the section on Malaysia and Dr. Shang-Jyh Hwang for the section on Taiwan. The authors thank the patients; the donors; Mr. Charles Antwi; Professor Nii Otu Nartey, former Chief Executive Officer of the Korle Bu Teaching Hospital; and the doctors; especially Dr. Dwomoa Adu, Dr. Bernard Morton, Professor Michael Mate Kole, Mr. Andrew Ready; and the Transplant Links Community team who worked together to make transplantation possible in Ghana. The authors also thank Dr. Manar Bushra, Director of the Sudan National Center for Kidney Diseases and Surgery, for the statistics provided.

The views expressed in this commentary are solely the responsibility of the authors and they do not necessarily reflect the views, decisions, or policies of the institutions with which they are affiliated.

Appendix 1 │ Evolutionary pathway of CKD/ESKD integrated care in Taiwan

BNHI, Bureau of National Health Insurance; CKD, chronic kidney disease; DOH, Department of Health; eGFR, estimated glomerular filtration rate; ERA-EDTA, European Renal Association – European Dialysis and Transplant Association; ESKD, end-stage kidney disease; NBHP, National Bureau of Health Promotion; NGO, nongovernmental organization; NHI, National Health Insurance; PD, peritoneal dialysis; TSN, Taiwan Society of Nephrology; USRDS, United States Renal Data System.

Appendix 2 │ Work-up checklist for living donor kidney donation in Ghana

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Day 1:  A 62-year old, recently widowed male Hispanic patient, named Mr. Kevin Ulyses Blanco (K. U. B.) was brought in to the emergency department (ED) by his daughter for progressively worsening shortness of breath, fatigue, a lingering non-productive cough, and generalized edema. One month prior, he noticed dyspnea upon exertion, loss of appetite, nausea, vomiting and malaise, which he attributed to the flu. In the emergency department, he appeared anxious and pale, and had a dry yellow tint to the skin. He denied any chest pain, and he could not recall the last time he urinated. He has history of benign prostatic hyperplasia, diabetes mellitus type 2, hypertension, dyslipidemia, and renal insufficiency for the past two years. His ED assessment findings included: 1+ pedal edema, basilar crackles in the lungs bilaterally, and a scant amount of urine according to a bladder scan. His lab results indicated a glomerular filtration rate (GFR) of 12. Based on his subjective and objective symptoms, he was admitted with a diagnosis of progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). The plan of care was focused on managing his symptoms and consulting with his nephrologist regarding need for hemodialysis.

Day 3:  Mr. K.U.B had an AV graft placed in his forearm to receive dialysis and a dual-lumen hemodialysis catheter for temporary use. His symptoms were worsening despite medical interventions and hemodialysis was needed urgently. The plan was to continue his medications to manage anemia, HTN, diabetes, and renal disease. The nurse identified psychosocial stressors of financial concern and having to live alone with his worsening health condition. With his daughter living far away, he was worried he wouldn’t have support. He stated that he was worried about the financial burden of hemodialysis and struggled with facing the reality of his diagnosis and what his quality of life would be like in the next few years of his life. A recommendation was made for a social worker and psychiatric consult.

Day 8:  By the end of day 8, most of his acute symptoms had been relieved and he was stable enough to be discharged. He had been in contact with case management for his follow up appointment had been made with his primary physician and discharge teaching was given.

• What modifiable factors could Mr. K.U.B. have addressed to slow the progression of his renal disease?
• What collaborative interventions could be used to enhance his care and ensure continuity of care after discharge?
• What affect did uncontrolled hypertension and poor medication compliance have on his disease process?

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Chronic Kidney Disease (CKD) Case Study (45 min)

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Mr. Stinson is a 52-year-old male with a history of HTN, DM Type II, CKD, and CHF. He presented to the Emergency Department (ED) complaining of severe itching, nausea, and vomiting.  He appeared pale and is lethargic. He reported shortness of breath and the nurse notes crackles in his lungs. He has now been admitted to your unit.

What additional nursing assessments should be performed?

• Full set of vital signs
• Auscultate heart and lung sounds, as well as peripheral pulses
• Assess skin turgor and edema
• Assess the patient’s dialysis access site for functionality or bleeding

What diagnostic or lab tests would you expect the provider to order?

• Complete metabolic panel (electrolytes, renal function, etc.
• Complete blood count
• Possibly an ABG to assess for acidosis
• Possibly a BNP to assess volume overload and its effect on the heart

Upon further questioning, the patient reports he normally gets dialysis Monday, Wednesday, Friday, but that he skipped dialysis yesterday because he was “not feeling well”. He has +2 pitting edema in his legs. Vital signs are as follows:

HR 102 RR 24

BP 153/97 SpO 2 90%

The patient’s labs result and show the following:

BUN 62 mg/dL Na 134 mg/dL

Cr 3.9 mg/dL Ca 7.8 mg/dL

GFR 13 mL/min/m 2 Phos 5.0 mg/dL

K 6.3 mEq/L Mg 1.6 mg/dL

Gluc 224 mg/dL H/H 8.2 / 30%

pH 7.32 pCO 2 32 HCO 3 – 16

BNP 247 pg/mL

Interpret these lab results and explain their meaning.

• The BUN/Cr and GFR indicate the patient is definitely in kidney failure as his glomerulus is not filtering the blood like it should and the waste products are building up
• His electrolyte abnormalities (hyperkalemia, hyponatremia, hypocalcemia, hyperphosphatemia, and hypomagnesemia) are all indicative of kidney disease and acidosis. The kidneys would normally retain sodium and excrete potassium. In kidney failure, they do the opposite and potassium levels can get very high.
• He is in metabolic acidosis, likely because his kidneys are not able to retain the bicarb buffer like they normally would – this also contributes to the hyperkalemia. As the body tries to balance the H+ ions, it kicks K+ out into the bloodstream.
• His BNP is also elevated, indicating volume overload – this is probably caused both by the kidney failure and not getting dialysis and by the heart failure
• He is anemic – chronic anemia is common in chronic kidney disease patients due to the lack of erythropoietin.

What is going on with Mr. Stinson physiologically?

• Because of his CKD, Mr. Stinson requires dialysis to perform the normal functions of the kidneys, since his aren’t working. He likely felt sick because his potassium was elevated and because of the azotemia (toxins building up in his blood).
• He missed dialysis and therefore he is now even more volume overloaded and azotemic
• This will cause a risk to his heart and lungs because of the overload and the hyperkalemia

The nephrologist is consulted and determines that the patient needs hemodialysis. As soon as possible.  The charge nurse of the dialysis unit is working to create a bed for him and will call back as soon as one is available, hopefully within the hour.

What do you, the nurse, need to consider and assess for Mr. Stinson PRIOR to sending him to dialysis?

• ALWAYS hold antihypertensives before HD (obtain provider order)
• Hold any medications that may be dialyzed off as they will not have their therapeutic benefit (confirm with pharmacist and obtain provider order)
• May require potassium-lowering medications before dialysis if the wait is going to be too long – hyperkalemia can be deadly
• Determine if any medications should be held prior to HD
• Assess full set of vital signs
• Obtain a weight, preferably on a standing scale
• Assess heart and lung sounds, as well as skin/edema

Mr. Stinson goes to hemodialysis, where they are able to pull of 3 L of fluid. He tolerates the procedure well and returns to his room.  

What would you need to assess for Mr. Stinson AFTER he returns from Dialysis?

• Obtain a weight, preferable on a standing scale, to compare to the pre-HD weight. This helps determine how much fluid was pulled off (1 kg = 1 L)
• Obtain a full set of vital sign
• Re-draw a renal function panel as ordered to ensure electrolytes are not in a dangerous range (requires provider order)

What are some important patient education topics for Mr. Stinson before discharge?

• Importance of hemodialysis – he likely didn’t feel well because he NEEDED dialysis.
• Reasons to “skip” dialysis typically involve severe infections and fevers, in which case he should go the following day whenever possible or notify his nephrology team
• Should also reinforce teaching regarding nutrition – foods to avoid (high in potassium) and when to take medications with or without food (especially Phos-Lo and Calcium supplements)

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Nursing Case Studies

This nursing case study course is designed to help nursing students build critical thinking.  Each case study was written by experienced nurses with first hand knowledge of the “real-world” disease process.  To help you increase your nursing clinical judgement (critical thinking), each unfolding nursing case study includes answers laid out by Blooms Taxonomy  to help you see that you are progressing to clinical analysis.We encourage you to read the case study and really through the “critical thinking checks” as this is where the real learning occurs.  If you get tripped up by a specific question, no worries, just dig into an associated lesson on the topic and reinforce your understanding.  In the end, that is what nursing case studies are all about – growing in your clinical judgement.

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• Published: 10 January 2022

Chronic kidney disease and its health-related factors: a case-control study

• Mousa Ghelichi-Ghojogh 1 ,
• Mohammad Fararouei 2 ,
• Mozhgan Seif 3 &
• Maryam Pakfetrat 4  

BMC Nephrology volume  23 , Article number:  24 ( 2022 ) Cite this article

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Chronic kidney disease (CKD) is a non-communicable disease that includes a range of different physiological disorders that are associated with abnormal renal function and progressive decline in glomerular filtration rate (GFR). This study aimed to investigate the associations of several behavioral and health-related factors with CKD in Iranian patients.

A hospital-based case-control study was conducted on 700 participants (350 cases and 350 controls). Logistic regression was applied to measure the association between the selected factors and CKD.

The mean age of cases and controls were 59.6 ± 12.4 and 58.9 ± 12.2 respectively ( p  = 0.827). The results of multiple logistic regression suggested that many factors including low birth weight (OR yes/no  = 4.07, 95%CI: 1.76–9.37, P  = 0.001), history of diabetes (OR yes/no  = 3.57, 95%CI: 2.36–5.40, P  = 0.001), history of kidney diseases (OR yes/no  = 3.35, 95%CI: 2.21–5.00, P  = 0.001) and history of chemotherapy (OR yes/no  = 2.18, 95%CI: 1.12–4.23, P  = 0.02) are associated with the risk of CKD.

Conclusions

The present study covered a large number of potential risk/ preventive factors altogether. The results highlighted the importance of collaborative monitoring of kidney function among patients with the above conditions.

Peer Review reports

Chronic kidney disease (CKD) is a non-communicable disease that includes a range of different physiological disorders that are associated with an abnormal renal function and progressive decline in glomerular filtration rate (GFR) [ 1 , 2 , 3 ]. Chronic kidney disease includes five stages of kidney damage, from mild kidney dysfunction to complete failure [ 4 ]. Generally, a person with stage 3 or 4 of CKD is considered as having moderate to severe kidney damage. Stage 3 is broken up into two levels of kidney damage: 3A) a level of GFR between 45 to 59 ml/min/1.73 m 2 , and 3B) a level of GFR between 30 and 44 ml/min/1.73 m 2 . In addition, GFR for stage 4 is 15–29 ml/min/1.73 m 2 [ 4 , 5 ]. It is reported that both the prevalence and burden of CKD are increasing worldwide, especially in developing countries [ 6 ]. The worldwide prevalence of CKD (all stages) is estimated to be between 8 to 16%, a figure that may indicate millions of deaths annually [ 7 ]. According to a meta-analysis, the prevalence of stage 3 to 5 CKD in South Africa, Senegal, and Congo is about 7.6%. In China, Taiwan, and Mongolia the rate of CKD is about 10.06% and in Japan, South Korea, and Oceania the rate is about 11.73%. In Europe the prevalence of CKD is about 11.86% [ 8 ], and finally, about 14.44% in the United States and Canada. The prevalence of CKD is estimated to be about 11.68% among the Iranian adult population and about 2.9% of Iranian women and 1.3% of Iranian men are expected to develop CKD annually [ 9 ]. Patients with stages 3 or 4 CKD are at much higher risk of progressing to either end-stage renal disease (ESRD) or death even prior to the development of ESRD [ 10 , 11 ].

In general, a large number of risk factors including age, sex, family history of kidney disease, primary kidney disease, urinary tract infections, cardiovascular disease, diabetes mellitus, and nephrotoxins (non-steroidal anti-inflammatory drugs, antibiotics) are known as predisposing and initiating factors of CKD [ 12 , 13 , 14 ]. However, the existing studies are suffering from a small sample size of individuals with kidney disease, particularly those with ESRD [ 15 ].

Despite the fact that the prevalence of CKD in the world, including Iran, is increasing, the factors associated with CKD are explored very little. The present case-control study aimed to investigate the association of several behavioral and health-related factors with CKD in the Iranian population.

Materials and methods

In this study, participants were selected among individuals who were registered or were visiting Faghihi and Motahari hospitals (two largest referral centers in the South of Iran located in Shiraz (the capital of Fars province). Cases and controls were frequency-matched by sex and age. The GFR values were calculated using the CKD-EPI formula [ 16 , 17 ].

Data collection

An interview-administered questionnaire and the participant’s medical records were used to obtain the required data. The questionnaire and interview procedure were designed, evaluated, and revised by three experts via conducting a pilot study including 50 cases and 50 controls. The reliability of the questionnaire was measured using the test-retest method (Cronbach’s alpha was 0.75). The interview was conducted by a trained public health‌ nurse at the time of visiting the clinics.

Avoiding concurrent conditions that their association may interpreted as reverse causation; the questionnaire was designed to define factors preceding at least a year before experiencing CKD first symptoms. Accordingly participants reported their social and demographic characteristics (age, sex, marital status, educational level, place of residency), history of chronic diseases (diabetes, cardiovascular diseases, hypertension, kidney diseases, family history of kidney diseases, autoimmune diseases and thyroid diseases [ 18 ]). Also history of other conditions namely (smoking, urinary tract infection (UTI), surgery due to illness or accident, low birth weight, burns, kidney pain (flank pain), chemotherapy, taking drugs for weight loss or obesity, taking non-steroidal anti-inflammatory drugs, and taking antibiotic) before their current condition was started. Many researchers reported recalling birth weight to be reliable for research purposes [ 19 ]. Moreover, we asked the participants to report their birth weight as a categorical variable (< 2500 g or low, 2500- < 3500 g or normal, and > 3500 g or overweight). Medical records of the participants were used to confirm/complete the reported data. In the case of contradiction between the self-reported and recorded data, we used the recorded information for our study.

Verbal informed consent was obtained from patients because the majority of the participants were illiterate. The study protocol was reviewed and approved by the ethical committee of Shiraz University of Medical Sciences (approval number: 1399.865).

Sample size

The sample size was calculated to detect an association‌ between the history of using antibiotics (one of our main study variables) and CKD as small as OR = 1.5 [ 20 ]. With an alpha value of 0.05 (2-sided) and a power of 80%, the required sample size was estimated as large as n  = 312 participants for each group.

Selection of cases

The selected clinics deliver medical care to patients from the southern part of the country. In this study, patients with CKD who were registered with the above centers from June to December 2020 were studied. A case was a patient with a GFR < 60 (ml/min/1.73 m 2 ) at least twice in 3 months. According to the latest version of the International Classification of Diseases (2010), Codes N18.3 and N18.4 are assigned to patients who have (GFR = 30–59 (ml/min/1.73 m 2 ) and GFR = 15–29 (ml/min/1.73 m 2 ) respectively [ 21 ]. In total, 350 patients who were diagnosed with CKD by a nephrologist during the study period.

Selection of the controls

We used hospital controls to avoid recall-bias. The control participants were selected from patients who were admitted to the general surgery (due to hernia, appendicitis, intestinal obstruction, hemorrhoids, and varicose veins), and orthopedic wards‌ from June to December 2020. Using the level of creatinine in the participants’ serum samples, GFR was calculated and the individuals with normal GFR (ml/min/1.73 m 2 ) GFR > 60) and those who reported no history of CKD were included ( n  = 350).

Inclusion criteria

Patients were included if they were ≥ 20 years old and had a definitive diagnosis of CKD by a nephrologist.

Exclusion criteria

Participants were excluded if they were critically ill, had acute kidney injury, those undergone renal transplantation, and those with cognitive impairment.

Statistical analysis

The Chi-square test was used to measure the unadjusted associations between categorical variables and CKD. Multiple logistic regression was applied to measure the adjusted associations for the study variables and CKD. The backward variable selection strategy was used to include variables in the regression model. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. All p -values were two-sided and the results were considered statistically significant at p  < 0.05. All analyses were conducted using Stata version 14.0 (Stata Corporation, College Station, TX, USA).

In total, 350 cases and 350 age and sex-matched controls were included in the analysis. The mean age of cases and controls were 59.6 ± 12.4 and 58.9 ± 12.2 respectively ( p  = 0.83). Overall, 208 patients (59.4%) and 200 controls (57.1%) were male ( p  = 0.54). Also, 149 patients (42.6%) and 133 controls (38.0%) were illiterate or had elementary education ( p  = 0.001). Most cases (96.9%) and controls (95.7%) were married ( p  = 0.42). The mean GFR for CKD and control groups were 38.6 ± 11.4 and 78.3 ± 10.2 (ml/min/1.73 m2) respectively.

Result of univariate analysis

Table  1 illustrates the unadjusted associations of demographic and health-related variables with CKD. Accordingly, significant (unadjusted) associations were found between the risk of CKD and several study variables including education, history of chronic diseases (diabetes, cardiovascular, hypertension, kidney diseases, autoimmune diseases, and hypothyroidism), family history of kidney diseases, smoking, UTI, surgery due to illness or accident, low birth weight, burns, kidney pain, chemotherapy, taking non-steroidal anti-inflammatory drugs, and taking antibiotics) ( P  < 0.05 for all).

Results of multivariable analysis

Table  2 illustrates the adjusted associations between the study variables and the risk of CKD. Most noticeably, low birth weight (OR yes/no  = 4.07, 95%CI: 1.76–9.37, P  = 0.001), history of surgery (OR yes/no  = 1.74, 95%CI: 1.18–2.54, P  = 0.004), family history of kidney diseases (OR yes/no  = 1.97, 95%CI: 1.20–3.23, P  = 0.007), and history of chemotherapy (OR yes/no  = 2.18, 95%CI: 1.12–4.23, P  = 0.02) were significantly associated with a higher risk of CKD. On the other hand, education (OR college/illiterate or primary  = 0.54, 95%CI: 0.31–0.92, P  = 0.025) was found to be inversely associated with CKD.

The results of the present study suggested that several variables including, education, history of diabetes, history of hypertension, history of kidney diseases or a family history of kidney diseases, history of surgery due to illness or accident, low birth weight, history of chemotherapy, history of taking non-steroidal anti-inflammatory drugs, and history of taking antibiotics may affect the risk of CKD.

In our study, the level of education was inversely associated with the risk of CKD. This finding is in accordance with the results of a study conducted by K Lambert et.al, who suggested that illiteracy or elementary education may raise the risk of CKD [ 22 ]. The fact that education level is associated with health literacy, may partly explain our results that lower education and inadequate health literacy in individuals with CKD is associated with worse health outcomes including poorer control of biochemical parameters, higher risk of cardiovascular diseases (CVDs); a higher rate of hospitalization, and a higher rate of infections [ 23 ].

In the current study, the history of diabetes was associated with a higher risk of CKD. This finding is consistent with the results of other studies on the same subject [ 20 , 21 , 24 , 25 , 26 , 27 ]. It is not surprising that people with diabetes have an increased risk of CKD as diabetes is an important detrimental factor for kidney functioning as approximately, 40% of patients with diabetes develop CKD [ 27 ].

The other variable that was associated with an increased risk of CKD was a history of hypertension. Our result is consistent with the results of several other studies [ 20 , 24 , 25 , 28 ]. It is reported that hypertension is both a cause and effect of CKD and accelerates the progression of the CKD to ESRD [ 29 ].

After controlling for other variables, a significant association was observed between family history of kidney diseases and risk of CKD. Published studies suggested the same pattern [ 24 ]. Inherited kidney diseases (IKDs) are considered as the foremost reasons for the initiation of CKD and are accounted for about 10–15% of kidney replacement therapies (KRT) in adults [ 30 ].

The importance of the history of surgery due to illness or accident in this study is rarely investigated by other researchers who reported the effect of surgery in patients with acute kidney injury (AKI), and major abdominal and cardiac surgeries [ 31 , 32 ] on the risk of CKD. Also, AKI is associated with an increased risk of CKD with progression in various clinical settings [ 33 , 34 , 35 ]. In a study by Mizota et.al, although most AKI cases recovered completely within 7 days after major abdominal surgery, they were at higher risk of 1-year mortality and chronic kidney disease compared to those without AKI [ 31 ].

The present study also showed that low birth weight is a significant risk factor for CKD. This finding is consistent with the results of some other studies. However, the results of very few studies on the association between birth weight and risk of CKD are controversial as some suggested a significant association [ 19 , 36 , 37 ] whereas others suggested otherwise [ 36 ]. This may be explained by the relatively smaller size and volume of kidneys in LBW infants compared to infants that are normally grown [ 38 ]. This can lead to long-term complications in adolescence and adulthood including hypertension, decreased glomerular filtration, albuminuria, and cardiovascular diseases. Eventually, these long-term complications can also cause CKD [ 39 ].

Another important result of the current study is the association between chemotherapy for treating cancers and the risk of CKD. According to a study on chemotherapy for testicular cancer by Inai et al., 1 year after chemotherapy 23% of the patients showed CKD [ 40 ]. Another study suggested that the prevalence of stage 3 CKD among patients with cancer was 12, and < 1% of patients had stage 4 CKD [ 41 , 42 ]. Other studies have shown an even higher prevalence of CKD among cancer patients. For instance, only 38.6% of patients with breast cancer, 38.9% of patients with lung cancer, 38.3% of patients with prostate cancer, 27.5% of patients with gynecologic cancer, and 27.2% of patients with colorectal cancer had a GFR ≥90 (ml/min/1.73 m 2 ) at the time of therapy initiation [ 43 , 44 ]. The overall prevalence of CKD ranges from 12 to 25% across many cancer patients [ 45 , 46 , 47 ]. These results clearly demonstrate that, when patients with cancer develop acute or chronic kidney disease, outcomes are inferior, and the promise of curative therapeutic regimens is lessened.

In our study, the history of taking nephrotoxic agents (antibiotics or NSAIDs drugs) was associated with a higher risk of CKD. Our result is following the results reported by other studies [ 48 , 49 ]. Common agents that are associated with AKI include NSAIDs are different drugs including antibiotics, iodinated contrast media, and chemotherapeutic drugs [ 50 ].

Strengths and limitations of our study

Our study used a reasonably large sample size. In addition, a considerably large number of study variables was included in the study. With a very high participation rate, trained nurses conducted the interviews with the case and control participants in the same setting. However, histories of exposures are prone to recall error (bias), a common issue in the case-control studies. It is to be mentioned that the method of selecting controls (hospital controls) should have reduced the risk of recall bias when reporting the required information. In addition, we used the participants’ medical records to complete/ confirm the reported data. Although the design of the present study was not able to confirm a causal association between the associated variables and CKD, the potential importance and modifiable nature of the associated factors makes the results potentially valuable and easily applicable in the prevention of CKD.

Given that, chemotherapy is an important risk factor for CKD, we suggest the imperative for collaborative care between oncologists and nephrologists in the early diagnosis and treatment of kidney diseases in patients with cancer. Training clinicians and patients are important to reduce the risk of nephrotoxicity. Electronic medical records can simultaneously be used to monitor prescription practices, responsiveness to alerts and prompts, the incidence of CKD, and detecting barriers to the effective implementation of preventive measures [ 51 ]. Routine follow-up and management of diabetic patients is also important for the prevention of CKD. We suggest a tight collaboration between endocrinologists and nephrologists to take care of diabetic patients with kidney problems. In addition, surgeons in major operations should refer patients, especially patients with AKI, to a nephrologist for proper care related to their kidney function. Treatment of hypertension is among the most important interventions to slow down the progression of CKD [ 12 ]. Moreover, all patients with newly diagnosed hypertension should be screened for CKD. We suggest all patients with diabetes have their GFR and urine albumin-to-creatinine ratio (UACR) checked annually. Finally, the aging population and obesity cause the absolute numbers of people with diabetes and kidney diseases to raise significantly. This will require a more integrated approach between dialectologists/nephrologists and the primary care teams (55).

Availability of data and materials

The datasets generated and/or analyzed during the current study are not publicly available due to their being the intellectual property of Shiraz University of Medical Sciences but are available from the corresponding author on reasonable request.

Abbreviations

• Chronic kidney disease

End-stage renal disease

Glomerular filtration rate

Renal replacement treatment

Urinary tract infection

Odds ratios

Confidence intervals

Hypertension

Acute kidney injury

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Acknowledgments

This paper is part of a thesis conducted by Mousa Ghelichi-Ghojogh, Ph.D. student of epidemiology, and a research project conducted at the Shiraz University of Medical sciences (99-01-04-22719). We would like to thank Dr. Bahram Shahryari and all nephrologists of Shiraz‌ University of medical sciences, interviewers, and CKD patients in Shiraz for their voluntary participation in the study and for providing data for the study.

Shiraz University of Medical Sciences financially supported this study. (Grant number: 99–01–04-22719).

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Mozhgan Seif

Nephrologist, Shiraz Nephro-Urology Research Center, Department of Internal Medicine, Emergency Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

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MGG: Conceptualization, Methodology, Statistical analysis, Investigation, and writing the draft of the manuscript. MP: were involved in methodology, writing the draft of the manuscript, and clinical consultation. MS: was involved in the methodology and statistical analysis. MF: was involved in conceptualization, methodology, supervision, writing, and reviewing the manuscript. The authors read and approved the final manuscript.

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Ghelichi-Ghojogh, M., Fararouei, M., Seif, M. et al. Chronic kidney disease and its health-related factors: a case-control study. BMC Nephrol 23 , 24 (2022). https://doi.org/10.1186/s12882-021-02655-w

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• Published: 27 March 2024

Community pharmacist-led point-of-care eGFR screening: early detection of chronic kidney disease in high-risk patients

• Ammar Abdulrahman Jairoun 1 , 2 ,
• Sabaa Saleh Al-Hemyari 2 , 3 ,
• Moyad Shahwan 4 , 5 ,
• Samer H. Zyoud 4 , 6 &
• Faris El-Dahiyat 7 , 8  

Scientific Reports volume  14 , Article number:  7284 ( 2024 ) Cite this article

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• Kidney diseases
• Medical research

Adherence to scheduled physician screenings for renal function monitoring in patients with chronic kidney disease (CKD) or those at high risk remains suboptimal despite the endorsement of regular screenings by several clinical practice guidelines. Our study aims to assess the effectiveness of a point-of-care CKD screening program led by these pharmacists using the PICCOLO device while recognizing the unique position of community pharmacists in primary care. We conducted an 11-month prospective point-of-care interventional research study in the United Arab Emirates to evaluate the performance of a community pharmacist-led CKD screening program for high-risk patients. Six diverse community pharmacies were selected based on staff availability, patient volume, and their offered range of services. Eligible individuals with risk factors for CKD were identified during medication evaluations. The PICCOLO Comprehensive Metabolic Panel facilitated on-site blood analysis, delivering estimated Glomerular Filtration Rate (eGFR) results within 10 to 15 min. Data also included eGFR categories, demographic information, and insights into lifestyle and health habits collected through a questionnaire. Pharmacists conducted comprehensive medication reviews and offered referrals and lifestyle guidance as part of the program. The study encompassed a total of 400 patients, with an average age of 69 ± 13.4 years within the study cohort. Notably, 38.8% (155 individuals) of the 400 patients were found to have undiagnosed CKD stages 3–5. Univariate logistic regression analysis revealed a significant association between a higher incidence of CKD stages 3–5 and factors such as older age, a history of hypertension, vascular disease, and diabetes mellitus. In the multivariate regression model, age and a history of diabetes mellitus emerged as significant predictors of an elevated risk of CKD. This study sheds light on the viability and impact of CKD screening programs conducted by community pharmacists, particularly in detecting CKD stages 3–5. The findings have implications for healthcare policies, as they can influence the enhancement of early detection and management of CKD. Moreover, these insights may catalyze focused screening initiatives and strengthen collaboration between community pharmacies and healthcare systems to benefit patients at high risk of CKD.

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Prevalence and Risk Factors of Chronic Kidney Disease among Type 2 Diabetes Patients: A Cross-Sectional Study in Primary Care Practice

Janjira Jitraknatee, Chidchanok Ruengorn & Surapon Nochaiwong

Epidemiology and risk of cardiovascular disease in populations with chronic kidney disease

Kunihiro Matsushita, Shoshana H. Ballew, … Rajiv Agarwal

Introduction

According to the classifications established by the Kidney Disease Improving Global Outcomes (KDIGO) and the Kidney Disease Outcomes Quality Initiative (KDOQI), there is a global increase in chronic kidney disease (CKD), impacting roughly 3% to 18% of the world's population 1 . CKD is characterized by irreversible renal damage or loss in sustained kidney function lasting longer than 3 months, often progressing slowly over months to years 2 . It is typically identified by a permanent decrease in renal function, defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 , or the presence of other markers of kidney damage, such as albuminuria ≥ 3 mg/mmol, abnormalities in urine sediment, or renal imaging anomalies, all persisting for more than 3 months 1 . Furthermore, CKD significantly contributes to elevated rates of morbidity and mortality in the general population, serving as an independent risk factor for cardiovascular disease and hypertension 1 .

In the last two decades, there has been a notable increase in the global occurrence of CKD, impacting 13.4% of the global population, primarily concentrated in stages 3–5 of the disease 3 . Recent data indicate that 2.8% of females and 4.6% of males in the United Arab Emirates (UAE) are in these advanced stages of CKD 4 . These statistics might only represent conservative approximations, especially considering the elevated prevalence of well-documented CKD risk factors within the United Arab Emirates (UAE) 5 .

In the UAE, hypertension (HTN) has witnessed a significant increase over the last 20 years, emerging as a major contributor to CKD 6 , 7 , 8 . Additionally, type 2 diabetes mellitus (DM), another significant risk factor 9 , 10 , affects 29% of UAE citizens 11 . Furthermore, the population of the United Arab Emirates exhibits higher than average rates of smoking, dyslipidemia, and obesity—all well-known cardiovascular risk factors—than people in wealthier countries 12 , 13 . It is well-recognized that these modifiable cardiovascular risk factors influence the rate of CKD progression 14 , 15 , 16 , 17 , 18 , particularly when several risk factors coexist 19 , 20 , 21 .

Due to the rarity or non-specificity of early symptoms, 90% of cases go undetected 22 . This allows the disease to progress into later stages silently, often only detected when renal failure becomes acute or when patients reach stage 5 CKD (eGFR < 15 mL/min) 22 , 23 . Advanced CKD stages not only necessitate hemodialysis or transplantation but can also bring about symptoms such as weight loss, vomiting, anorexia, pruritus, or muscle cramps. Complications of CKD and the subsequent end-stage renal disease (ESRD) encompass anemia, bone abnormalities, a heightened risk of cardiovascular disease, and an increased risk of all-cause mortality 23 .

Early intervention is the key to reducing the morbidity and mortality linked to chronic kidney disease (CKD) 24 . Yet, the silent nature of CKD in its initial stages raises concerns about the feasibility of timely detection as recommended by clinical guidelines. In primary care, many patients either receive insufficient treatment or remain undiagnosed 25 . Therefore, a critical imperative is to conduct focused and easily accessible screening, particularly for high-risk individuals, including those with diabetes, hypertension, a family history of kidney disease, or cardiovascular disease 26 . In this context, community pharmacists assume a unique and pivotal role in delivering targeted Chronic Kidney Disease (CKD) screening, effectively serving as the vanguard of primary care. A notable initiative in this regard is the application of the CKD Clinical Pathway, previously outlined 26 . The efficacy of this strategy has been assessed in Alberta, Canada 27 . Under their authority, pharmacists conducted, ordered, and interpreted laboratory tests, as demonstrated in the study by Al Hamarneh et al. 27 , 28 . Impressively, 720 high-risk patients were successfully screened for CKD following the CKD Clinical Pathway, revealing that 40% of the individuals examined had CKD, with 40% of this subgroup previously undiagnosed 27 .

While the incidence of CKD in the UAE and other Arab nations remains unknown 29 , establishing local data is paramount to comprehending the epidemiological aspects of CKD in the high-risk population. The primary objective of this study is to ascertain the prevalence of chronic kidney disease (CKD) among high-risk patients by evaluating the effectiveness of a point-of-care screening program led by community pharmacists utilizing the PICCOLO device. Furthermore, the study aims to identify the CKD risk factors most predictive of previously undetected renal function impairment within the community pharmacy setting, serving as its secondary goal.

Methods and materials

Study design and setting.

This prospective point-of-care interventional study spanned from January 1st to November 30th, 2023, with the primary aim of investigating the prevalence of chronic kidney disease (CKD) in high-risk patients and evaluating the effectiveness of a point-of-care screening program administered by community pharmacists. The study was conducted at six carefully selected community pharmacies in the United Arab Emirates, encompassing both chain and independent establishments, and participation was voluntary and random.

The choice of these pharmacies was deliberate, based on specific criteria. They were chosen for their substantial patient volume and the comprehensive range of services, including medication reviews, management of chronic diseases, prescription medication dispensing, recommendations for over-the-counter (OTC) medications, as well as nutrition and dietary counseling. Additionally, these pharmacies had the requisite personnel capable of conducting the study with precision and competence.

Study population (inclusion and exclusion criteria)

During the process of medication evaluation, individuals, both UAE nationals and non-UAE nationals, were considered eligible for participation if they exhibited at least one of the following recognized risk factors for chronic kidney disease (CKD): diabetes, hypertension, a history of cardiovascular illness, a family history of renal disease, or an age above 55 years.

To be eligible for participation in the study, individuals had to meet the following criteria: Aged 18 or over and meet at least one of the following conditions under the KDIGO International Guidelines, rendering them at risk for CKD:

Diabetes mellitus (either type 1 or type 2).

Hypertension.

A documented family history of kidney disease.

Sample size calculation

Given a reported CKD prevalence of 4.6% among males and 2.8% among females in the UAE 3 and considering the recent study's findings revealing an 11.4% incidence of CKD stages 3–5 30 , we initially anticipated that the percentage of individuals with CKD stages 3–5 in our study would approximate 12%.. Our chosen significance level (alpha) was 5% to produce 95% confidence intervals. Moreover, we aimed for a precision (D) of 5% within these 95% confidence intervals to ensure a broad 95% range of ± 10%.

Based on these underlying assumptions, we determined that a minimum sample size of n = 312 participants would be necessary, factoring in an estimated nonresponse rate of approximately 50%. Consequently, our final sample size was established at 400 participants.

Data collection

Patients visiting the pharmacy for prescription drop-off or pick-up were identified as potential participants. Those who met the eligibility criteria were then approached and invited to join the study, receiving comprehensive information about its purpose and procedures. Subsequently, they were requested to provide written informed consent indicating their willingness to participate.

The pharmacy's staff pharmacists oversaw the consent process and facilitated utilizing the on-site PICCOLO Comprehensive Metabolic Panel and blood chemistry analyzer for data collection. Once the necessary data had been gathered, additional consent was sought from patients to allocate a unique participant ID, ensuring both confidentiality and anonymity in the use of their data for research purposes. Patients were allowed to share their demographic and result information anonymously voluntarily.

Intervention and measurement tool

A disposable lancet was employed to extract a venous blood sample through a self-administered fingerstick, following the prior cleaning of the finger with an alcohol swab.

To prevent significant hemolysis, the initial blood drop was carefully wiped away. Subsequently, a minimum sample volume of 100 μL was acquired through capillary action and gentle finger pressure at the puncture site, allowing for the collection of successive drops into a designated collection tube. Following this, the pharmacist pipetted the collected material into a metabolic panel disc to prepare it for analysis using the PICCOLO instrument. Once the blood was placed within the panel disc, it underwent heparinization and was spun into cuvette wells that contained dry sample blank reagent beads. These beads were equipped with the necessary reagents, buffers, surfactants, and excipients for absorption chemistry analysis 32 .

The PICCOLO blood chemistry analyzer utilized the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) research equation and the creatinine levels assessed by the panel to estimate the Glomerular Filtration Rate (eGFR) for each patient, incorporating the provided age, gender, and race data 31 , 32 . Typically, results were available within a span of 10 to 15 min.

PICCOLO instrument

The PICCOLO device, when deployed at the point of care, serves as a portable diagnostic analyzer offering a comprehensive array of CLIA-waived blood chemistry tests. CLIA-waived blood tests are those exempt from the Clinical Laboratory Improvement Amendments (CLIA) requirements in the United States. Irrespective of the testing location, the CLIA federal regulatory framework establishes quality standards for all laboratory testing, ensuring precision, reliability, and the swift delivery of patient test results. Tests deemed straightforward with a low risk of inaccurate results and those considered user-friendly fall under the waived category.

The PICCOLO instrument represents an innovative, fully automated tool employed at the point of care across diverse healthcare settings, including pediatric offices, oncology clinics, urgent care centers, and physician's offices. In blood testing, CLIA-waived tests are typically uncomplicated point-of-care procedures that can be conducted outside traditional laboratory settings.

Meeting a wide range of clinical chemistry needs, the PICCOLO Xpress delivers real-time blood chemistry diagnostic information within minutes. Despite its compact size, this PICCOLO instrument excels in accuracy, reliability, and repeatability.

These tests are designed for individuals without laboratory backgrounds, such as healthcare professionals working in clinics, pharmacies, or other point-of-care settings. They often require minimal technical expertise. Depending on their waiver status, certain more stringent regulatory requirements applicable to more complex laboratory processes are waived for these tests.

Study variables

An estimated Glomerular Filtration Rate (eGFR) of 90 or higher indicated normal renal function. An eGFR falling within the range of 60 to 89 (CKD Stage 2) signified a mild impairment in renal function, while an eGFR in the 30 to 59 range (CKD Stage 3) indicated a significant reduction in renal function.

Each participant completed a paper-based questionnaire during this phase, providing additional insights into the specific risk factor for which they were selected to participate. This questionnaire collected data on demographics (age, gender), lifestyle factors, and health characteristics (such as tobacco use, body mass index [BMI], history of diabetes, hypertension, kidney disease, vascular disease, and family history of renal disease). Additionally, the pharmacist conducted a comprehensive medication review with each patient and made tailored recommendations, which might include dietary adjustments or referrals to their primary care physician when necessary. These recommendations were grounded in the patient's medication history and risk factors, relying on the pharmacist's professional judgment.

Ethical approval

The study received approval from the Institutional Ethical Review Committee of Ajman University (Approval Number: P-H-S-2022-2-9). All methods were carried out under relevant guidelines and regulations. Before collecting data, all participants were duly informed about the study's objectives and explicitly consented to completing the questionnaire. Written informed consent was obtained from all respondents. To safeguard participant anonymity, no information was gathered that could potentially disclose their identities, and rigorous measures were implemented to uphold the confidentiality of participant data.

Statistical analyses

For data analysis, we utilized SPSS Version 26. Continuous variables with a normal distribution were assessed using means and standard deviations (SD), while categorical variables were analyzed through frequencies and percentages. We employed one-way ANOVAs, nonparametric alternatives, and unpaired Student t-tests to identify disparities among quantitative variables. In order to determine the variables that exerted an influence on CKD, we applied univariate and multivariate logistic regression models. Statistical significance was defined when p < 0.05.

Demographics and comorbidities of the study cohort

A total of 400 patients were enrolled in the study. The mean age of the study cohort was 69 ± 13.4 years. The mean eGFR was 76.3 ± 27 mL/min/1.73 m 2 . Of the total, 43% (n = 172) were male and 10% (n = 40) were smokers. The comorbidities among the study cohort were as follows: vascular disease (n = 180, 45%), Hypertension (n = 346, 86.5%) and Diabetes Mellitus (n = 129, 32.3%) (Table 1 ).

eGFR estimated glomerular filtration rate.

Prevalence of unrecognized CKD by community pharmacist-directed point-of-care screening program

Table 2 displays the prevalence of various CKD stages categorized by patients' demographics and comorbidities. A statistically significant difference in eGFR levels was observed based on age (P < 0.001), vascular disease (P = 0.037), hypertension (P = 0.001), and diabetes mellitus (P < 0.001).

In our study cohort of 400 patients, 155 patients had unrecognized/undiagnosed CKD (38.8%). The results of univariate logistic regression revealed an increased prevalence of CKD stages 3–5 associated with older age (OR 1.099, 95% CI 1.075–1.123, p < 0.001), a history of hypertension (OR 1.66, 95% CI 1.015–2.73, p = 0.043), a history of vascular disease (OR 1.528, 95% CI 1.349–1.798, p = 0.002), a history of hypertension (OR 4.25, 95% CI 1.95–9.27, p < 0.001), and a history of diabetes mellitus (OR 2.86, 95% CI 1.85–4.41, p = 0.001) (Table 3 ).

In the multivariate regression model, after a backward stepwise selection, the significant predictors that increased the risk of CKD stages 3–5 included older age (OR 1.090, 95% CI 1.064–1.116, p < 0.001) and a history of diabetes mellitus (OR 2.095, 95% CI 1.260–3.485, p = 0.004) (Table 3 ).

Compliance with scheduled physician screenings for renal function remains alarmingly inadequate, with rates fluctuating between a mere 28% and a modest 75%, despite the advocacy of numerous clinical practice guidelines for regularly monitoring chronic kidney disease (CKD) in CKD patients and those at elevated risk 33 . Community pharmacies, with their accessibility and convenience, hold promise as potential game-changers, motivating a more significant number of patients to undergo testing 34 . Anecdotal feedback from pharmacists has highlighted the value of CKD screening for patients, the successful integration of such screening into their workflow, and its role in setting their pharmacies apart in a competitive landscape.

Notably, this study breaks new ground by examining the effectiveness of a point-of-care screening program led by community pharmacists for early detection of abnormal renal function in high-risk patients, employing an on-site PICCOLO Comprehensive Metabolic Panel and blood chemistry analyzer. Our research underscores the feasibility and viability of implementing point-of-care testing for CKD screening within a community pharmacy context. In the course of our investigation, it came to light that 155 patients (38.8%) exhibited CKD stages 3–5, a condition that had not previously been recognized or diagnosed. This contrasts with earlier studies in diverse populations and nations, where undiagnosed CKD was comparatively less prevalent. For instance, Donovan et al. reported an 11% incidence of CKD, with 90% of cases going undetected 35 .

Similarly, Arora et al. found that 12.5% of adult Canadians had CKD, based on data from the Canadian Health Measures Survey 36 . Our findings align with prior research conducted both in community and laboratory settings 22 , 37 . Additionally, the SeeKD study 2016 revealed that 18.8% of 6329 patients with at least one CKD risk factor had undiagnosed CKD 38 .

Using a multivariate regression model and employing a backward stepwise selection process, we pinpointed that a history of diabetes mellitus and advancing age consistently emerge as significant predictors for a heightened risk of developing CKD stages 3–5. These robust associations underscore the importance of considering age and diabetes mellitus history when assessing CKD risk, in line with findings from previous studies 36 . As a result, our findings strongly support the adoption of tailored interventions and screening tactics, especially among older demographics and those with a background of diabetes mellitus. These measures are pivotal in improving the timely identification and control of CKD. These identified risk factors underscore the need for proactive healthcare practices and public health campaigns to raise awareness and promote preventative measures within populations at risk for chronic kidney disease. This aligns with the emphasis placed on such strategies by Al Hamarneh and colleagues, who utilized laboratory testing to screen high-risk individuals for CKD 27 .

The implications of this research extend into optimizing medication regimens and developing strategies to mitigate the progression of CKD by addressing risk factors, including cardiovascular events. These findings have profound implications for patient care 39 , 40 , 41 . Despite the robust evidence supporting pharmacists' involvement in laboratory testing 28 , it is worth noting that this practice has not been widely adopted across most jurisdictions 35 .

The current study successfully demonstrated the feasibility of implementing a pharmacist-guided point-of-care screening program for chronic kidney disease (CKD) within a community pharmacy setting. Additionally, our study has uncovered a significant proportion of previously undiagnosed CKD cases. Given the frequent misdiagnosis and inadequate treatment of CKD, the role of pharmacists in its detection and management is paramount. This has far-reaching implications for enhancing patient access to care, prognostic outcomes, cardiovascular risk management, and drug dosage optimization. Furthermore, it underscores the indispensable role of pharmacists within the broader spectrum of pharmacy practice.

In the context of community pharmacy, our study sheds light on the prevalence and risk factors associated with CKD stages 3–5. The substantial percentage of our study participants with previously undetected CKD (38.8%) underscores the critical importance of adopting proactive screening initiatives, especially among older adults and those with a history of diabetes mellitus.

Our findings emphasize the significance of diabetes mellitus and age as independent predictors of CKD stages 3–5, even considering other comorbid and demographic factors. This highlights the imperative need for targeted interventions and educational programs aimed at these high-risk populations, ultimately enhancing the early identification and management of CKD.

The utilization of point-of-care testing within a community pharmacy setting underscores the potential extension of screening services beyond traditional healthcare settings. This approach emphasizes the valuable contribution of community pharmacies to public health initiatives, aligning with the overarching goal of promoting preventive healthcare.

However, it is important to acknowledge the limitations of this research. The possibility of selection bias during pharmacist recruitment and the requirement for patients to provide informed consent may have excluded individuals with known CKD or those unwilling to participate. Additionally, potential recall bias may exist since demographic data relied on self-reporting and dispensing history. The absence of follow-up at the end of the 3 months poses a challenge in confirming CKD, as CKD is a condition that evolves over time, and diagnosis requires multiple eGFR readings. Furthermore, the assessment of the impact of pharmacist interventions on patients with low eGFR was constrained by the lack of follow-up. For a more precise evaluation, the KDIGO 2012 guideline recommends categorizing CKD based on both GFR and albumin levels 33 . Unfortunately, the pharmacy's inability to collect and analyze urine samples precluded the categorization of patients according to the KDIGO criteria.

Our research offers significant insights into the occurrence and determinants of advanced CKD stages (3–5) within the context of community pharmacies. This valuable information has the potential to guide healthcare policies, promote focused screening initiatives, and strengthen the collaborative partnership between community pharmacies and healthcare systems. Ultimately, these efforts aim to enhance the early detection and effective management of CKD.

Data availability

The original contributions presented in the study are included in the further inquiries that can be directed to the corresponding authors.

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Acknowledgements

MS is highly grateful to Ajman University for all necessary support to accomplish the project successfully. We want to thank our colleagues for participating in this study and supporting our work in this way; they helped us obtain results of better quality.

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Ammar Abdulrahman Jairoun

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Clinical Pharmacy Program, College of Pharmacy, Al Ain University, 64141, Al Ain, United Arab Emirates

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A.A.J and S.S.A Conceptualization and Methodology, M.S and S.Z data collection and visualization. A.A.J and S.Z software. A,A,J and FE Data analysis and interpretation. S.S.A and M.S Drafted the original Manuscript. All authors reviewed and approved the final manuscript. All authors agreed to the publication of this manuscript in Scientific Reports.

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Jairoun, A.A., Al-Hemyari, S.S., Shahwan, M. et al. Community pharmacist-led point-of-care eGFR screening: early detection of chronic kidney disease in high-risk patients. Sci Rep 14 , 7284 (2024). https://doi.org/10.1038/s41598-024-56765-0

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Optimizing chronic kidney disease management through a learning health system approach

by Health Data Science

A recent publication in Health Data Science offers an in-depth exploration of an innovative approach to chronic kidney disease (CKD) management through the adoption of a learning health system (LHS) model. The study underscores a transformative shift towards more responsive and efficient health care practices, especially in managing pervasive conditions like CKD.

In the realm of medicine, the journey from research discovery to clinical application is notoriously protracted, often spanning nearly two decades. The LHS framework seeks to dramatically shorten this trajectory by leveraging real-time data analytics, thereby expediting the translation of research insights into practical health care interventions.

Associate Research Professor Guilan Kong of the National Institute of Health Data Science (NIHDS) at Peking University highlights the critical role of LHS in accelerating the data-to-evidence-to-practice continuum, an advancement he views as crucial for improving global health outcomes in the digital age.

Targeting CKD, a condition that is both widespread and undermanaged in China, the research team piloted an LHS initiative in Yinzhou, a district distinguished by its sophisticated Regional Health Information Platform (YRHIP) operational since 2009. This platform, integral to the local health care landscape, collects comprehensive patient data across various medical institutions and has been instrumental in developing a specialized CKD surveillance system initiated in 2018.

The project's inception involved assembling a diverse learning community, including medical practitioners , IT specialists, and data scientists, who collaboratively assessed CKD care in Yinzhou, identifying and addressing critical care delivery gaps. This collective effort enabled the identification of CKD patients through an advanced computable tool, facilitating targeted intervention by primary care providers.

The researchers emphasize the potential of integrating predictive analytics and clinical decision support mechanisms into the YRHIP, aiming to enhance patient triage, streamline referrals, and encourage the adoption of clinical guidelines.

Professor Luxia Zhang of NIHDS reflects on the pilot's promising outcomes, suggesting that a robust LHS infrastructure can significantly catalyze the adoption of evidence-based health care solutions. Although LHS models are prevalent in more affluent settings, their application in less economically developed regions presents unique challenges and opportunities for innovation.

As the team looks to the future, they plan to refine CKD predictive analytics and further integrate these technologies into Yinzhou's health care framework, a step Prof Kong believes will empower physicians to make more informed decisions, thereby elevating the standard of CKD care.

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SYSTEMATIC REVIEW article

Effect of uric acid reduction on chronic kidney disease. systematic review and meta-analysis.

• 1 Toxicology Unit, Universidad de Salamanca, Salamanca, Spain
• 2 Instituto de Investigación Biomédica de Salamanca (IBSAL) del Instituto de Ciencias de la Salud de Castilla y León (ICSCYL), Salamanca, Spain
• 3 Department of Physiology and Pharmacology, Universidad de Salamanca (USAL), Salamanca, Spain
• 4 Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain
• 5 National Network for Kidney Research REDINREN, RICORS2040 RD21/0005/0004-Instituto de Salud Carlos III, Madrid, Spain
• 6 Group of Biomedical Research on Critical Care (BioCritic), Valladolid, Spain

Accumulating evidence suggests that hyperuricemia is a pathological factor in the development and progression of chronic kidney disease. However, the potential benefit afforded by the control of uric acid (UA) is controversial. Individual studies show discrepant results, and most existing meta-analysis, especially those including the larger number of studies, lack a placebo or control group as they aim to compare efficacy between drugs. On these grounds, we performed a me-ta-analysis restricted to studies including the action of any anti-gout therapies referenced to a control or placebo arm. This approach allows for a clearer association between UA reduction and renal effect. Of the twenty-nine papers included, most used allopurinol and febuxostat and, therefore, solid conclusions could only be obtained for these drugs. Both were very effective in reducing UA, but only allopurinol was able to significantly improve glomerular filtration rate (GFR), although not in a dose-dependent manner. These results raised doubts as to whether it is the hypouricemic effect of anti-gout drugs, or a pleiotropic effect, what provides protection of kidney function. Accordingly, in a correlation study that we next performed between UA reduction and GFR improvement, no association was found, which suggests that additional mechanisms may be involved. Of note, most trials show large inter-individual response variability, probably because they included patients with heterogeneous phenotypes and pathological characteristics, including different stages of CKD and comorbidities. This highlights the need to sub classify the effect of UA-lowering therapies according to the pathological scenario, in order to identify those CKD patients that may benefit most from them.

Systematic Review Registration: CRD42022306646 https://www.crd.york.ac.uk/prospero/

1 Introduction

Chronic kidney disease (CKD) is defined as evidence of abnormalities in renal structure or function for at least 3 months, with implications for health ( Stevens, 2013 ) including increased bone and cardiovascular morbidity, and significantly reduced life expectancy and quality of life ( Ortiz, 2022 ). Patients in terminal stages (i.e., a 0.13% of the whole population) become dependent on costly replacement therapy in the form of dialysis or renal transplant ( Ortiz, 2022 ). Due to its high prevalence and the absence of an effective treatment, CKD is one of the leading causes of mortality worldwide ( Kovesdy, 2022 ). It is estimated that 10% of the adult population suffers from some degree of CKD, and that by 2100 CKD will be the second leading cause of death from disease ( Ortiz, 2022 ). These data show the need to develop strategies to reduce these numbers, and measures for the prophylactic mitigation of its causes. Several factors have been associated with the risk of developing CKD. Non-modifiable factors include age, sex, race or family history, while others can be averted, treated pharmacologically or reduced, such as obesity, hypertension, diabetes and the use of tobacco or analgesics ( Kazancioğlu, 2013 ). In the last decades, hyperuricemia has been proposed as a potential risk factor for CKD ( Feig, 2020 ).

Hyperuricemia, an excess of uric acid (UA) in the blood, is a common cause of gout ( Brook et al., 2010 ). In 1940, it was observed that a high number of patients with gout also suffered from kidney disorders ( Coombs et al., 1940 ). A later study indicated that 90% of autopsied patients with gout also had kidney damage (glomerulosclerosis, tubulointerstitial fibrosis, and arteriosclerosis) ( Talbott and Terplan, 1960 ). It was suggested that kidney damage was caused by the deposit of urate crystals found in the tubules and the interstitium in these patients. Subsequent studies with animal models confirmed that urate crystals directly cause tubular damage, in part mediated by oxidative stress ( Sánchez-Lozada et al., 2002 ). However, additional pathological factors related to hyperuricemia could exist because urate deposits have also been detected in gouty patients with no evidence of renal damage ( Yü and Berger, 1982 ). Furthermore, a preclinical study determined that mild and transient hyperuricemia, in the absence of urate deposits, also aggravated and accelerated CKD ( Mazzali et al., 2001 ). Other proposed mechanisms of kidney damage caused by hyperuricemia include mitochondrial dysfunction, renin-angiotensin system overactivation, and endothelial dysfunction produced by a reduction of nitric oxide and excessive release of vasoconstrictors (e.g., endothelin and thromboxane) ( Mazzali et al., 2001 ; Mallat et al., 2016 ; Bonino et al., 2020 ).

If hyperuricemia plays a significant role in CKD, reducing its levels should have a beneficial effect on renal function (i.e., slowing down or reverting disease progression). In this regard, controversial evidence exists. While numerous clinical studies support a renoprotective effect of hypouricemic therapy [reviewed in ( Richette et al., 2018 )], others did not find a positive association [reviewed in ( Leoncini et al., 2022 )]. Meta-analyses that have been performed to date ( Bose et al., 2014 ; 2014 ; Chen et al., 2020 ; Sun et al., 2020 ; Liu et al., 2021 ; Tsukamoto et al., 2021 ; Gonçalves et al., 2022 ) included trials in which the comparator was placebo, usual care, or an alternative medicine, in a mixed manner. Almost invariably, existing meta-analyses only ascribe protection to those treatments that improve renal function and, thus, may underestimate their efficacy. A strict comparison versus placebo/control is necessary to discern whether anti gout treatments improve renal function or merely slow down its progressive decay. Accordingly, with the objective of studying the effect of hyperuricemia-lowering strategy on renal function in CKD, we meta-analyzed only those studies containing a placebo/control arm and carried out a correlation study between hypouricemic efficacy and renal protection.

The protocol of this systematic review is registered in PROSPERO with the code CRD42022306646 (25/02/2022). The entire procedure described below was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

2.1 Systematic study mining

A bibliographic search of articles published up to September 2023 in MEDLINE and the Web of Science databases was carried out. MeSH terms and keywords were used in order to maximize article mining. In the PUBMED platform, the MeSH terms used were “Chronic Renal Insufficiency” [Mesh]) and “Gout Suppressors” [Pharmacological Action]. In both platforms, the terms were used independently as follows “((“Kidney Failure, Chronic”) OR (“Chronic Kidney Failure”) OR (“Chronic Kidney Injury”) OR (Renal Failure, Chronic) OR (Chronic Renal Injury) OR (chronic renal disease) OR (CKD) OR (CKF)) AND ((“Gout Suppressants”) OR (Allopurinol) OR (Benzbromarone) OR (benziodarone) OR (Colchicine) OR (Febuxostat) OR (halofenate) OR (Probenecid) OR (sulfinpyrazone) OR (tricrynafen) OR (zoxazolamine) OR (pegloticase) OR (rasburicase) OR (losartan))”. In both cases, the human filter was added to select only clinical trials. Subsequently, an additional search was carried out introducing each drug individually along with the terms specified for kidney damage, which further enhanced article identification.

2.2 Inclusion and exclusion criteria

First, two members of the research team (A.G.C. and L.V.-V.) independently identified those studies that met at least one of the following exclusion criteria: 1) reviews, protocols, case-reports, congress abstracts, editor letters or comments; 2) pre-clinical studies; 3) only abstract available; 4) unrelated content; or 5) language other than English, Spanish, Italian, French or Portuguese. Among the remaining studies, only those that met all the following inclusion criteria were definitively selected: 1) Randomized studies in which urate-lowering therapy is administered in patients with CKD; 2) Studies that evaluate renal function by estimated Glomerular Filtration Rate (eGFR), serum creatinine (sCr), albuminuria or proteinuria [reporting the mean and a measure of dispersion that allow calculation of the standard deviation (SD)]; 3) Studies that present baseline and follow-up data; and 4) Studies that include a control or placebo group. After comparing the list of articles selected by both researchers, a third member of the team (A.I.M.) was designated to resolve potential discrepancies.

2.3 Data extraction

The following data were extracted from each selected article: study reference (first author and year of publication), design, location, patient recruitment dates, type of population, number of patients in the treated group and in the placebo/control group, evaluated treatment (drug, dose and duration of treatment). Clinical study design quality was calculated according to the Jadad scale ( Jadad et al., 1996 ) (studies with a score of five were considered rigorous, scores between three and five were considered good quality, and scores below three were considered poor quality (and were eliminated). Additionally, the mean SD values of the parameters serum uric acid (sUA), eGFR, sCr, albuminuria and/or proteinuria were registered (or calculated from the standard error of the mean or the confidence interval). When verifying that only two studies evaluated albuminuria, it was decided to dispense with this biomarker. From these numerical data, the mean increase in each biomarker (BM Δ ) was calculated in the treated and the control/placebo groups with the formula: BM Δ = BM F − BM B , where BM F is the mean value of the biomarker at the end of the nephroprotective treatment, and BM B is the mean baseline value of the biomarker. The standard deviation resulting from this difference, s Δ , was also calculated as the accumulation of errors: s Δ = s F 2 + s B 2 , where s F is the SD value of the biomarker at the end of the nephroprotective treatment, and s B is the SD value of the biomarker at baseline. Since most of the included studies evaluated the drugs allopurinol and febuxostat, these analyzes were performed independently for each of these treatments and for an additional group of drugs called ‘Others'.

2.4 Meta-analysis

Heterogeneity between studies was assessed with the Cochran’s Q test under the null hypothesis of homogeneity ( p < 0.05 indicated heterogeneity) and the I 2 index (I 2 > 50% indicated high heterogeneity). After this, the fixed-effects model (for homogeneous studies) or the random-effects model (for heterogeneous studies) was selected to meta-analyze the data. The Hedges’ g value and its 95% confidence interval were calculated for each study and each renal function biomarker with the following formula:

where BM Δ T and BM Δ C/P are the biomarker increases in the treatment and in the control/placebo groups, respectively; s ∆ T 2 and s ∆ C / P 2 are the standard deviations of the treatment and the control/placebo groups, respectively; and n T and n C / P correspond to the sizes of the treatment and control/placebo groups, respectively. Forest plots were constructed in which the g parameters of the different included studies were compared.

Finally, funnel plots in which the Hedges’ g of each study was represented versus its standard error were constructed to evaluate potential publication bias. In addition, the asymmetry tests of Begg and Mazumdar ( Begg and Mazumdar, 1994 ) and Egger et al. ( Egger et al., 1997 ) were applied. All the analyses described in this section were carried out with the Meta-Essentials set of workbooks ( Suurmond et al., 2017 ).

2.5 Correlation study

In order to study the relationship between the ability of the tested treatments to reduce sUA levels and to improve renal function, a Pearson correlation test was performed (for normal data, which was previously verified with the Saphiro-Wilk test). Only the treated groups of those studies that quantified both evolution in sAU and eGFR from the start to the end of treatment were included. p -values lower than 0.05 were considered statistically significant. This analysis was performed with the IBM SPSS Statistics 20.0 software (International Business Machines, Armonk, NY, United States).

3.1 Description of included studies

A flowchart of the search process followed for the selection of the 29 clinical studies finally included is presented in Figure 1 ( Katholi et al., 1998 ; Siu et al., 2006 ; Kanbay et al., 2007 ; Malaguarnera et al., 2009 ; Nouri-Majalan, 2009 ; Zhu et al., 2009 ; Goicoechea et al., 2010 ; 2015 ; Momeni et al., 2010 ; Kao et al., 2011 ; Shi et al., 2012 ; Sezer et al., 2014 ; Bayram et al., 2015 ; Sircar et al., 2015 ; Golmohammadi et al., 2017 ; Krishnamurthy et al., 2017 ; Ghane Sharbaf and Assadi, 2018 ; Kimura et al., 2018 ; Wada et al., 2018 ; Johnson et al., 2019 ; Lee and Lee, 2019 ; Badve et al., 2020 ; Doria et al., 2020 ; Perrenoud et al., 2020 ; Wen et al., 2020 ; Jeyaruban et al., 2021 ; Stack et al., 2021 ; Nata et al., 2023 ; Yang et al., 2023 ).

Figure 1 . Flowchart of the search process.

The descriptive data extracted from the clinical studies included in this meta-analysis are shown in Table 1 . Total patients add up to 4,471 (44.1% receiving an UA-lowering therapy). The drug predominantly used is allopurinol followed by febuxostat.

Table 1 . Characteristics of the clinical studies included in this meta-analysis. CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; i.v., intravenous; n.a., not applicable; n.d., not described; p.o., per os (orally); Prot, proteinuria; SCr, serum creatinine concentration; sUA, serum uric acid concentration.

3.2 Results of the meta-analysis

3.2.1 hypouricemic efficacy.

The ability of the treatments to reduce sUA levels in the clinical trials included in this study is summarized in Figure 2 . The two most evaluated compounds (allopurinol and febuxostat) significantly reduce sUA levels in 88% and 100% of the trials, respectively. Although higher for febuxostat, the combined meta-analytical result is very favorable for both drugs. In the case of allopurinol, higher effectiveness was observed for doses over 100 mg/day (regardless of the duration of treatment). In contrast, in the case of febuxostat, all tested doses (between 20 and 80 mg) showed similar beneficial effects. On the other hand, among the therapies evaluated to a lesser extent, only topiroxostat showed a highly significant hypouricemic effect.

Figure 2 . Meta-analytical results of the uric acid-lowering capacity of the therapies evaluated in the included clinical trials. Data are shown as a forest plot representing the difference in the means between the treated group and the control/placebo group for each trial. Effect size is measured as Hedges’ g ± 95% CI. CI: confidence interval; GFR, glomerular filtration rate; w, weeks.

3.2.2 Nephroprotective effect

Most of the included trials evaluated the nephroprotective effect through the eGFR. The results of their meta-analysis are presented in Figure 3 .

Figure 3 . Meta-analytic results of the ability of evaluated therapies to improve or prevent eGFR deterioration. Data are shown as a forest plot representing the difference in the means between the treated and the control/placebo groups for each trial. Effect size is measured as Hedges’ g ± 95% CI. CI: confidence interval; d, days; eGFR, estimated glomerular filtration rate; w, weeks.

The combined result for allopurinol shows a significant nephroprotective effect. Of note, in practically all the studies, the effect on eGFR showed a very high interindividual variability. However, the tendency in almost all the studies using allopurinol shows a beneficial effect on their patients. In no case renal function worsened. In the case of febuxostat, only three studies using the 20 or 20–80 mg/day dosage demonstrated a significant nephroprotective effect. A beneficial effect on renal function was also seen in the only trial using rasburicase or topiroxostat.

Some of the selected clinical trials also evaluated kidney function using sCr and urinary protein excretion. The results of the meta-analysis for these parameters are shown in Figures 4 , 5 , respectively.

Figure 4 . Meta-analytic results of the ability of evaluated therapies to reduce or prevent the in-crease of SCr levels. Data are shown as a forest plot showing the difference in the means between the treated and the control/placebo groups. Effect size is measured as Hedges’ g ± 95% CI. CI: confidence interval; d, days; GFR, glomerular filtration rate; w, weeks.

Figure 5 . Meta-analytic results of the ability of evaluated therapies to reduce or prevent the in-crease in proteinuria. Data are shown as a forest plot showing the difference in the means between the treated and the control/placebo groups. Effect size is measured as Hedges’ g ± 95% CI. CI: confidence interval; w, weeks.

No significant effects were observed on these two biomarkers for any of the drugs evaluated except for a slight nephroprotective effect observed in a study using 100–200 mg alopurinol, and an evident effect for rasburicase, both on sCr. No study showed a significant effect on proteinuria.

3.2.3 Evaluation of publication bias

The results of the publication bias assessment are shown in Figure 6 . Data distribution and asymmetry tests show a notorious publication bias ( p < 0.01) for sUA. However, this bias does not affect the object of this meta-analysis, which is focused on whether the anti-gout, hypouricemic therapy exerts beneficial effects on CKD, not on whether the anti-gout therapy reduces uricemia. The asymmetry on sUA is expected, as all the drugs used in the included studies are known to be efficient at reducing hyperuricemia. Moreover, mild publication bias is also found for the eGFR. Specifically, graphical analysis identifies absence of treatments considerably worsening renal function. However, this is not real bias either, because all drugs tested are under clinical use. If deemed nephrotoxic, for ethical reasons they would never be administered to patients with CKD.

Figure 6 . Funnel plots and asymmetry tests corresponding to the meta-analysis of sUA (A) , eGFR (B) , SCr (C) and proteinuria (D) . Effect size is measured as Hedges’ g ± 95% CI. CES: combined effect size; CI: confidence interval.

3.3 Correlation study

The relationship between sUA reduction and improvement or prevent of eGFR deterioration (a standard renal function biomarker mostly evaluated in the included clinical trials) was studied with the Pearson test. As shown in Figure 7 , no correlation was observed between both parameters for any of the drugs evaluated, nor for all of them in general. These results indicate that there is no direct or proportional relationship between them, which suggests that additional mechanisms other than the reduction of sUA contribute to the nephroprotective effect.

Figure 7 . Graphical representation and correlation analysis of the average reductions in serum uric acid versus the average increases in estimated glomerular filtration rate.

4 Discussion

Inclusion of a control/placebo group in the evaluation of the nephroprotective effect of hypouricemic therapy in CKD yields only a relevant number of studies for two drugs, allopurinol and febuxostat, from which convincing conclusions can be drawn. Our study demonstrates that both drugs positively affect glomerular filtration, with allopurinol showing a bolder effect. However, this limited casuistry is insufficient to infer whether there is a class effect of hypouricemic therapies on CKD, or the benefits exerted by allopurinol and febuxostat are due to additional mechanisms unrelated to the reduction of UA and specific of these two drugs. To overcome this limitation, a correlation analysis was carried out between the degree of UA reduction and the degree of renal protection for all the drugs included in the study. The results showed that reducing hyperuricemia is beneficial for renal function, but not in a directly proportional manner.

Proportionality might be disrupted by two factors. On the one hand, study population heterogeneity. A large inter-individual variability in the renal effect of antigout therapy is evidenced by the long error bars observed in virtually all the studies. This individual variability may be explained by the enrolment of patients at different stages of CKD and with different risk factors, whose renal damage patterns are heterogeneously caused by hyperuricemia and, thus, respond differentially to hypouricemic therapy. Identifying the phenotype and pathological scenario in which hypouricemic therapy provides nephroprotection to CKD patients poses an immediate research challenge. In this sense, some studies suggest that reducing UA may be more effective in preventing kidney damage in younger people ( Feig, 2020 ) and in the early stages of CKD, which requires confirmation.

On the other hand, additional mechanisms unrelated to UA reduction could uncouple the apparent relationship of the hypouricemic effect on the nephroprotection observed between drugs and between patients. In this regard, allopurinol and febuxostat have strong antioxidant properties as both drugs are xanthine oxidase inhibitors ( Becker et al., 2005 ; Schumacher et al., 2008 ). Several authors propose this mechanism as the main responsible for their nephroprotection ( Okafor et al., 2017 ; Cicero et al., 2021 ). However, antioxidants alone are not enough to prevent CKD ( Casanova et al., 2021 ). A marked anti-inflammatory effect on the vascular endothelium has also been reported for both allopurinol ( Goicoechea et al., 2010 ) and febuxostat ( Becker et al., 2005 ; Schumacher et al., 2008 ). Febuxostat has also been shown to prevent CKD progression in nephrectomized, normouricemic rats, by preserving preglomerular vessel morphology and maintaining glomerular pressure, which unveils an additional protective effect independently of UA levels ( Sanchez-Lozada et al., 2018 ).

Another important observation from this meta-analysis is that, overall, renal protection is not dependent on drug dose or treatment duration. One possible reason is that in some clinical trials the dose was adjusted as treatment progressed, while in others it was not. This could affect the results since possibly not all patients received the most appropriate dose.

Interestingly, protection has been observed even in short-term treatments (i.e., 4–16 weeks) ( Kanbay et al., 2007 ; Momeni et al., 2010 ; Bayram et al., 2015 ; Ghane Sharbaf and Assadi, 2018 ; Perrenoud et al., 2020 ; Wen et al., 2020 ). This suggests that, in addition to impinging on slower chronic processes of kidney injury underlying CKD progression, hypouricemic agents may also ameliorate renal function by a relatively swift mechanism. For instance, an improvement in endothelial function bestowed by antioxidant and anti-inflammatory effects and by increased nitric oxide availability ( Khosla et al., 2005 ; Schwartz et al., 2011 ), may cause renal vasodilation, increase renal blood flow and GFR, and explain the faster response seen in some patients. Distinct acute effects also contribute to the variable effect exerted by different drugs, and for the same drug between patients.

Thus, the overall effect of a drug in a specific study depends on the heterogeneous composition of pathophysiological patterns in the population studied, as determined stochastically or by environmental and social factors. Individual responses depend, in turn, on how the pharmacological mechanisms of the drug used match the patient’s pathophysiological pattern. In perspective, personalized antigout therapy in CKD should be based on the election of the appropriate drug/dose for each scenario.

Of note, only two of the 29 articles included in this meta-analysis considered albuminuria in assessing renal function, despite its importance in the diagnosis of CKD ( Hallan et al., 2009 ). In fact, albuminuria complements the GFR, improves CKD diagnosis, risk stratification, and prognosis of progression ( Hallan et al., 2009 ; Polkinghorne, 2014 ; Lambers Heerspink and Gansevoort, 2015 ), and forms part of the Kidney Disease Improving Global Outcomes guidelines (i.e., the international consensus diagnostic criteria) since 2012 ( KDIGO, 2013 ). While GFR only informs on status of the glomerular filtration process, increased albuminuria may reflect a change in glomerular permselectivity and a defect in tubular function, specifically in tubular reabsorption ( Levey et al., 2020 ; Divya et al., 2023 ). Incomplete renal function diagnosis may cause misinterpretation of the effect of hypouricemic therapies. Curiously, this affects studies performed both before and after public availability of the KDIGO guidelines. We contend that future clinical trials designed to evaluate the nephroprotective effect of UA-lowering therapy should collect both GFR and albuminuria values for a more granular detection of the pathophysiological spectrum underlying CKD.

In conclusion, this work shows that the reduction of hyperuricemia might potentially be an effective strategy in the prevention of CKD in specific pathological scenarios, which needs to be further explored. The phenotype of patients who may benefit from this therapy should be the focus of future studies.

Data availability statement

The raw data supporting the conclusion of this article will be made available by the authors, without undue reservation.

Author contributions

AC: Writing–original draft, Methodology, Formal Analysis, Data curation. AM: Writing–review and editing, Methodology, Formal Analysis. LV-V: Writing–original draft, Methodology, Formal Analysis, Conceptualization. FL-H: Writing–review and editing, Supervision, Formal Analysis, Conceptualization.

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project “PI20/01,351”and co-funded by the European Union; and RICORS 2040, RD21/0005/0004, co-funded by the European Union–NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR)

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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Keywords: uric acid-lowering therapy, chronic kidney disease, protection, prevention, allopurinol

Citation: Casanova AG, Morales AI, Vicente-Vicente L and López-Hernández FJ (2024) Effect of uric acid reduction on chronic kidney disease. Systematic review and meta-analysis. Front. Pharmacol. 15:1373258. doi: 10.3389/fphar.2024.1373258

Received: 19 January 2024; Accepted: 14 March 2024; Published: 26 March 2024.

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Copyright © 2024 Casanova, Morales, Vicente-Vicente and López-Hernández. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Laura Vicente-Vicente, [email protected]

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