Abstract
The global burden of chronic kidney disease (CKD) is increasing with a projection of becoming the five leading causes of years-of-life-lost globally by 2040. CKD is a major cause of catastrophic health expenditure. The costs of dialysis and transplantation consume up to 3% of the entire annual healthcare budget in high-income countries. Crucially, however, both the onset and progression of CKD is potentially preventable.
In 2020, the World Kidney Day campaign highlights the importance of preventive interventions – be it primary, i.e., to prevent de no CKD, or secondary or tertiary, i.e., prevention of worsening early CKD or progression of more advanced CKD to end-stage kidney disease, respectively. Primary prevention should focus on the modification of CKD risk factors and addressing structural abnormalities of the kidney and urinary tracts, and exposure to environmental risk factors and nephrotoxins. In persons with preexisting kidney disease, secondary prevention, including blood pressure optimization, glycemic control and avoiding high-protein high-sodium diet should be the main goal of education and clinical interventions. In patients with moderate to advanced CKD, management of comorbidities such as uremia and cardiovascular disease along with low-protein diet are among the recommended preventative interventions to avoid or delay dialysis or kidney transplantation.
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Whereas national policies and strategies for non-communicable diseases may exist in a country, specific policies directed toward education and awareness about CKD screening, prevention, and treatment are often lacking. There is an urgent need to increase awareness for preventive measures throughout populations, professionals and policy makers.
Introduction
Around 850 million people currently are affected by different types of kidney disorders.1 Up to 1 in 10 adults worldwide has chronic kidney disease (CKD), which is invariably irreversible and mostly progressive. The global burden of CKD is increasing, and CKD is projected to become the fifth most common cause of years of life lost globally by 2040.2 If CKD remains uncontrolled and if the affected person survives the ravages of cardiovascular and other complications of the disease, CKD progresses to end-stage kidney disease, where life cannot be sustained without dialysis therapy or kidney transplantation. Hence, CKD is a major cause of catastrophic health expenditure.3 The costs of dialysis and transplantation consume 2%–3% of the annual health care budget in high-income countries, spent on less than 0.03% of the total population of these countries.4
Importantly, however, kidney disease can be prevented and progression to end-stage kidney disease can be delayed with appropriate access to basic diagnostics and early treatment including lifestyle modifications and nutritional interventions.4–8 Despite this access to effective and sustainable health care provision programs, kidney care remains highly inequitable across the world. Indeed, of parallel importance is the ongoing health inequity in CKD care including inequity of health care access particularly among some of the indigenous populations in certain regions of the world, and this may have a bearing on the preexisting and emerging health gaps between low-middle-income, middle-income, and high-income countries. Kidney disease is crucially missing from the international agenda for global health. It is notably absent from the impact indicators for the Sustainable Development Goal Goal 3, Target 3.4, “By 2030, reduce by one third premature mortality from noncommunicable diseases (NCDs) through prevention and treatment and promote mental health and well-being,” and the latest iteration of the United Nations Political Declaration on NCDs.9 CKD is a major risk factor for heart disease and cardiac death, as well as for infections such as tuberculosis, and is a major complication of other preventable and treatable conditions including diabetes, hypertension, HIV, and hepatitis.4–7 Moreover, consumer engagement and self-help management are crucial to improving kidney health. To that end, the World Kidney Day steering committee suggests adopting strategies that focus on preventative interventions.
Definition and classification of CKD prevention
According to the expert definitions including the Center for Disease Control and Prevention,10 the term “prevention” refers to activities that are typically categorized by the following 3 definitions: (i) primary prevention implies intervening before health effects occur in an effort to prevent the onset of illness or injury before the disease process begins, (ii) secondary prevention suggests preventive measures that lead to early diagnosis and prompt treatment of a disease to prevent more severe problems developing and includes screening to identify diseases in the earliest stages, and (iii) tertiary prevention indicates managing disease after it is well established in order to control disease progression and the emergence of more severe complications, which is often by means of targeted measures such as pharmacotherapy, rehabilitation, and screening for and management of complications. These definitions have important bearing in the prevention and management of CKD, and accurate identification of risk factors that cause CKD or lead to faster progression to renal failure, as shown in Figure 1, is relevant in health policy decisions and health education and awareness related to CKD.11
Primary prevention of CKD
Measures to achieve effective primary prevention should focus on the 2 leading risk factors for CKD including diabetes mellitus and hypertension. Other CKD risk factors include polycystic kidneys or other congenital or acquired structural anomalies of the kidney and urinary tracts, primary glomerulonephritis, exposure to nephrotoxic substances or medications (such as nonsteroidal anti-inflammatory drugs), having 1 single kidney, for example, solitary kidney after cancer nephrectomy, high dietary salt intake, inadequate hydration with recurrent volume depletion, heat stress, exposure to pesticides and heavy metals (as has been speculated as the main cause of Mesoamerican nephropathy), and possibly high protein intake in those at higher risk of CKD.8 Among nonmodifiable risk factors are advancing age and genetic factors such as apolipoprotein 1 (APOL1) gene that is mostly encountered in those with sub-Saharan African ethnicity, especially among African Americans. Table 1 shows some of the risk factors of CKD.
Among measures to prevent emergence of de novo CKD are screening efforts to identify and manage persons at high risk of CKD, especially those with diabetes mellitus and hypertension. Hence, targeting primordial risk factors of these 2 conditions including metabolic syndrome and overnutrition is relevant to primary CKD prevention as is correcting obesity.12 Promoting healthier lifestyle includes physical activity and healthier diet. The latter should be based on more plant-based foods with less meat, less sodium intake, more complex carbohydrates with higher fiber intake, and less saturated fat. In those with hypertension and diabetes, optimizing blood pressure and glycemic control has shown to be effective in preventing diabetic and hypertensive nephropathies. Persons with solitary kidney should avoid high protein intake above 1 gram per kilogram body weight per day.13,14 Obesity should be avoided, and weight reduction strategies should be considered.12
An emerging challenge relevant to these primary preventive efforts is the rise of a new form of CKD that is of “unknown etiology” and is, hence, referred to as “CKDu,” which has resulted in substantial morbidity and mortality including in certain regions of the world with heavy agricultural occupation such as Nicaragua and Sri Lanka.15 There are currently concerted efforts by the international nephrology community to identify the potential modifiable and nonmodifiable risk factors of CKDu, and to develop potential interventions to mitigate the burden of this emerging disease state.
Secondary prevention in CKD
Evidence suggests that among those with CKD, the vast majority have early stage of the disease, that is, CKD stages 1 and 2 with microalbuminuria (30–300 mg/d) or CKD stage 3B (estimated glomerular filtration rate between 45 and 60 ml/min per 1.73 m2).14 For these earlier stages of CKD, the main goal of kidney health education and clinical interventions for “secondary prevention” is how to slow disease progression. Uncontrolled or poorly controlled hypertension is one of the most established risk factors for faster CKD progression.
The cornerstone of the pharmacotherapy in secondary prevention is the renin-angiotensin-aldosterone system inhibitors. Low protein diet appears to have a synergistic effect on renin-angiotensin-aldosterone system inhibitor therapy.16 Recent data suggest that a new class of antidiabetic medications known as sodium-glucose cotransporter-2 inhibitors can slow CKD progression, but this effect may not be related to glycemic modulation of the medication.17 Whereas acute kidney injury may or may not cause de novo CKD, acute kidney injury events that are superimposed on preexisting CKD may accelerate disease progression.18 A relatively recent case of successful secondary prevention that highlights the significance of implementing preventive strategies in CKD is the use of a vasopressin V(2)-receptor antagonists in adult polycystic kidney disease.19
Tertiary prevention in CKD
In patients with advanced CKD, management of uremia and related comorbid conditions such as anemia, mineral and bone disorders, and cardiovascular disease is of high priority, so that these patients can continue to achieve highest longevity. Whereas many of these patients will eventually receive renal replacement therapy in the form of dialysis therapy or kidney transplantation, a new trend is emerging to maintain them longer without dialysis by implementing conservative management of CKD.
Approaches to identification of chronic kidney diseases
The lack of awareness of CKD around the world is one of the reasons for late presentation of CKD in both developed and developing economies.20–22 The overall CKD awareness among general population and even high cardiovascular risk groups across 12 low-income and middle-income countries was less than 10%.22
Given its asymptomatic nature, screening of CKD plays an important role in early detection. Consensus and Positional Statements have been published by International Society of Nephrology,23 National kidney Foundation,24 Kidney Disease Improving Global Outcomes,25 National Institute of Clinical Excellence (NICE) Guidelines,26 and Asian Forum for CKD Initiatives.27 Most guidelines do not recommend population-based screening because of the potential risk of overdiagnoses and the potential harms such as psychological burden of being labeled with CKD. There is also a lack of trial-based evidence to support routine screening and monitoring of CKD.28 Currently, most will promote a targeted screening approach to early detection of CKD. Some of the major groups at risk for targeted screening includes patients with diabetes and hypertension, those with family history of CKD, individuals receiving potentially nephrotoxic drugs or herbal medicines, patients with past history of acute kidney injury, and individuals older than 65 years.27,29 Early detection of CKD could be facilitated among high-risk groups using a urine test for the detection of proteinuria and a blood test to estimate the glomerular filtration rate.24,27 Given that low- to middle-income countries may be ill-equipped to deal with the devastating consequences of CKD, particularly the late stages of the disease, effective preventative measures to avoid CKD or to slow progression are of immense importance in these regions. There are suggestions that screening should primarily include high-risk individuals, but also extend to those with suboptimal levels of risk, for example, prediabetes and prehypertension.30
Cost-effectiveness of early detection programs
Secondary prevention of CKD relays on timely identification of early signs of CKD including hyperfiltration, microalbuminuria, microscopic hematuria, sporadic foamy urine, and minor elevations in serum creatinine level or other kidney filtration markers. Prior economic evaluations have indicated routine screening using estimated glomerular filtration rate, and urine tests are not cost-effective without risk stratification in the general population. The incremental cost-effectiveness ratios were consistently above $50,000 per life years saved or per quality-adjusted life years unless screening is targeted to higher risk populations, such as those with diabetes mellitus and hypertension and those with rapid CKD progression where routine use angiotensin pathway modulators could be used for renal and vascular risk reduction. To this end, it is important to note some of the key factors that may drive the incremental cost-effectiveness of CKD preventative measures in different regions and health care jurisdictions.
Integration of CKD prevention into national NCD programs
Given the close links between CKD and other NCDs, it is critical that CKD advocacy efforts be aligned with existing initiatives concerning diabetes, hypertension, and cardiovascular disease, particularly in the low- and middle-income countries. Some countries and regions have successfully introduced CKD prevention strategies as part of their NCD management programs. As an example, in 2003, a kidney health promotion program was introduced in Taiwan, with its key components including a ban on herbs containing aristolochic acid, public-awareness campaigns, patient education, funding for CKD research, and the setting up of teams to provide integrated care.31 In Cuba, the Ministry of Public Health has implemented a national program for the prevention of CKD. It is hoped that the integration of CKD prevention into the NCD program may result in the reduction of renal and cardiovascular risks in the general population. Over time there have been increasingly higher incidences of risk factors for CKD including higher rates of diabetes mellitus and hypertension, and parallel to that more blood pressure medications including renoprotective agents have been prescribed including angiotensin-pathway modulators.32,33 Recently, the US Department of Health and Human Services has introduced an ambitious program to reduce the number of Americans developing end-stage kidney disease by 25% by 2030. The program, known as the Advancing American Kidney Health Initiative, has set goals with metrics to measure its success; among them is to put more efforts to prevent, detect, and slow the progression of kidney disease, in part by addressing traditional risk factors such as diabetes and hypertension.34 Ongoing programs, such as the Special Diabetes Program for Indians, represent an important part of this approach by providing team-based care and care management. Since its implementation, the incidence of diabetes-related kidney failure among American Native populations decreased by over 40% between 2000 and 2015.35
The interdisciplinary prevention approach
Since 1994, a National Institutes of Health consensus advocated for early medical intervention in predialysis patients. Owing to the complexity of care of CKD, it was recommended that patients should be referred to a multidisciplinary team consisting of nephrologist, dietitian, nurse, social worker, and health psychologist, with the aim to reduce predialysis and dialysis morbidity and mortality.36 In Mexico, a nurse-led, protocol-driven, multidisciplinary program reported better preservation in estimated glomerular filtration rate and a trend in the improvement of quality of care of patients with CKD similar to those reported by other multidisciplinary clinic programs in the developed world.37 Future models should address region-specific causes of CKD, increase the quality of diagnostic capabilities, establish referral pathways, and provide better assessments of clinical effectiveness and cost-effectiveness.38
Online educational programs for CKD prevention and treatment
The e-learning has also become an increasingly popular approach to medical education. Online learning programs for NCD prevention and treatment, including CKD, have been successfully implemented in Mexico. By 2015, over 5000 health professionals (including non-nephrologists) had been trained using an electronic health education platform.39 It is equally important to promote “Prevention” with education programs for those at risk of kidney disease and with the general population at large. Education is key to engaging patients with kidney disease. It is the path to self-management and patient-centered care. Narva et al.40 found that patient education is associated with better patient outcomes. Obstacles include the complex nature of kidney disease information, low baseline awareness, limited health literacy, limited availability of CKD information, and lack of readiness to learn. Schatell et al.41 found that Web-based kidney education is helpful in supporting patient self-management. Reputable health care organizations should facilitate users to have easier access to health information on their websites (Supplementary Appendix S1). Engagements of professional society, patient groups, charitable, and philanthropic organizations promote community partnership and patient empowerment on prevention.
Renewed focus on prevention and awareness raising and education
Given the pressing urgency pertaining to the need for increasing education and awareness of the importance of the preventive measures, we suggest the following goals to redirect the focus on plans and actions:
- (i) Empowerment through health literacy in order to develop and support national campaigns that bring public awareness to prevention of kidney disease.
- (ii) Population-based approaches to manage key known risks for kidney disease, such as blood pressure control and effective management of obesity and diabetes.
- (iii) Implementation of the World Health Organization “Best Buys” approach including screening of at-risk populations for CKD, universal access to essential diagnostics of early CKD, availability of affordable basic technologies, and essential medicines and task shifting from doctors to front-line health care workers to more effectively target progression of CKD and other secondary preventative approaches.
“Kidney Health for Everyone, Everywhere” with emphasis on prevention and early detection should be a policy imperative that can be successfully achieved if policy makers, nephrologists, health care professionals and the general public place prevention and primary care for kidney disease within the context of their Universal Health Coverage programs.
APPENDIX
Members of the World Kidney Day Steering Committee are Philip Kam Tao Li, Guillermo Garcia-Garcia, Sharon Andreoli, Kamyar Kalantar-Zadeh, Latha Kumaraswami, Vassilios Liakopoulos, Siu-Fai Lui, Gamal Saadi, Luisa Strani, and Ifeoma Ulasi.
DISCLOSURE
All the authors declared no competing interests.
SUPPLEMENTARY MATERIAL
Appendix 1. Selected websites with information on CKD patient education.
REFERENCES
1. International Society of Nephrology. 2019United Nations High Level Meeting on UHC: Moving Together to Build Kidney Health worldwide; 2019. Available at: https://www.theisn.org/images/Advocacy_4_pager_2019_Final_WEB_pagebypage.pdf. Accessed July 20, 2019.
2. Foreman KJ, Marquez N, Dolgert A, et al. Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories. Lancet 2018;392:2052–2090.
3. Essue BM, Laba TL, Knaul F, et al. Economic burden of chronic ill health and injuries for households in low- and middle-income countries. In: Jamison DT, Gelband H, Horton S, et al, eds. Disease Control Priorities Improving Health and Reducing Poverty. 3rd ed. Washington, DC: World Bank; 2018: 121–143.
4. Vanholder R, Annemans L, Brown E, et al. Reducing the costs of chronic kidney disease while delivering quality health care: a call to action. Nat Rev Nephrol 2017;13:393–409.
5. Luyckx VA, Tuttle KR, Garcia-Garcia G, et al. Reducing major risk factors for chronic kidney disease. Kidney Int Suppl (2011) 2017;7:71–87.
6. Luyckx VA, Tonelli M, Stanifer JW. The global burden of kidney disease and the sustainable development goals. Bull World Health Organ 2018;96:414–422D.
7. Tonelli M, Muntner P, Lloyd A, et al. Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study. Lancet 2012;380:807–814.
8. Kalantar-Zadeh K, Fouque D. Nutritional management of chronic kidney disease. N Engl J Med 2017;377:1765–1776.
9. United Nations General Assembly. Political declaration of the third high-level meeting of theGeneral Assembly on the prevention and control ofnon-communicable diseases; 2018. Available at: https://www.un.org/ga/search/view_doc.asp?symbol=A/73/L.2&Lang=E. Accessed November 3, 2019.
10. Center for Disease Control and Prevention (CDC). Picture of America; 2017. At a Glance—Executive Summary 2019. Available at: www.cdc.gov/pictureofamerica. Accessed November 3, 2019.
11. Levey AS, Schoolwerth AC, Burrows NR, et al, Centers for Disease Control and Prevention Expert Panel. Comprehensive public health strategies for preventing the development, progression, and complications of CKD: report of an expert panel convened by the Centers for Disease Control and Prevention. Am J Kidney Dis 2009;53:522–535.
12. Kovesdy CP, Furth SL, Zoccali C, World Kidney Day Steering Committee. Obesity and kidney disease: hidden consequences of the epidemic. J Ren Nutr 2017;27:75–77.
13. Tantisattamo E, Dafoe DC, Reddy UG, et al. Current management of acquired solitary kidney. Kidney Int Rep 2019;4:1205–1218.
14. Webster AC, Nagler EV, Morton RL, Masson P. Chronic kidney disease. Lancet 2017;389:1238–1252.
15. Anand S, Caplin B, Gonzalez-Quiroz M, et al, International Society of Nephrology’s International Consortium of Collaborators on Chronic Kidney Disease of Unknown Etiology (i3C). Epidemiology, molecular, and genetic methodologies to evaluate causes of CKDu around the world: report of the Working Group from the ISN International Consortium of Collaborators on CKDu. Kidney Int 2019;96:1254–1260.
16. Koppe L, Fouque D. The role for protein restriction in addition to renin-angiotensin-aldosterone system inhibitors in the management of CKD. Am J Kidney Dis 2019;73:248–257.
17. Mayer GJ, Wanner C, Weir MR, et al. Analysis from the EMPA-REG OUTCOME® trial indicates empagliflozin may assist in preventing the progression of chronic kidney disease in patients with type 2 diabetes irrespective of medications that alter intrarenal hemodynamics. Kidney Int 2019;96:489–504.
18. Rifkin DE, Coca SG, Kalantar-Zadeh K. Does AKI truly lead to CKD? J Am Soc Nephrol 2012;23:979–984.
19. Torres VE, Chapman AB, Devuyst O, et al, TEMPO 3:4 Trial Investigators. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 2012;367:2407–2418.
20. Verhave JC, Troyanov S, Mongeau F, et al. Prevalence, awareness, and management of CKD and cardiovascular risk factors in publicly funded health care. Clin J Am Soc Nephrol 2014;9:713–719.
21. Chow KM, Szeto CC, Kwan B, et al. Public lacks knowledge on chronic kidney disease: telephone survey. Hong Kong Med J 2014;20:139–144.
22. Ene-Iordache B, Perico N, Bikbov B, et al. Chronic kidney diseaseand cardiovascular risk in six regions of the world (ISN-KDDC): a cross-sectional study. Lancet Glob Health 2016;4:e307–e319.
23. Li PKT, Weening JJ, Dirks J, et al. A report with consensus statements of the International Society of Nephrology 2004 Consensus Workshop on Prevention of Progression of Renal Disease. Kidney Int Suppl 2005;(94):s2–s7.
24. Vassalotti JA, Stevens LA, Levey AS. Testing for chronic kidney disease: a position statement from the National Kidney Foundation. Am J Kidney Dis 2007;50:169–180.
25. Levey AS, Atkins R, Coresh J, et al. Chronic kidney disease as a global public health problem: approaches and initiatives—a position statement from Kidney Disease Improving Global Outcomes. Kidney Int 2007;72:247–259.
26. Crowe E, Halpin D, Stevens P, Guideline Development Group. Early identification and management of chronic kidney disease: summary of NICE guidance. BMJ 2008;337:a1530.
27. Li PKT, Chow KM, Matsuo S, et al. Asian Chronic Kidney Disease (CKD) Best Practice Recommendations—positional statements for early detection of CKD from Asian Forum for CKD Initiatives (AFCKDI). Nephrology (Carlton) 2011;16:633–641.
28. Fink HA, Ishani A, Taylor BC, et al. Screening for, monitoring, and treatment of chronic kidney disease stages 1 to 3: a systematic review for the U.S. Preventive Services Task Force and for an American College of Physicians Clinical Practice Guideline. Ann Intern Med 2012;156:570–581.
29. Li PKT, Ng JK, Cheng YL, et al. Relatives In Silent Kidney disease Screening study (RISKS): a Chinese cohort study. Nephrology (Carlton) 2017;22(Suppl 4):35–42.
30. George C, Mogueo A, Okpechi I, et al. Chronic kidney disease in low-income to middle-income countries: the case for increased screening. BMJ Glob Health 2017;2:e000256.
31. Hwang SJ, Tsai JC, Chen HC. Epidemiology, impact and preventive care of chronic kidney disease in Taiwan. Nephrology (Carlton) 2010;15(Suppl 2):3–9.
32. Almaguer M, Herrera R, Alfonso J, et al. Primary health care strategies for the prevention of end-stage renal disease in Cuba. Kidney Int Suppl 2005;97:S4–S10.
33. Alamaguer-Lopez M, Herrera-Valdez R, Diaz J, Rodriguez O. Integration of chronic kidney disease prevention into noncommunicable disease programs in Cuba. In: Garcia-Garcia G, Agodoa LY, Norris KC, eds. Chronic Kidney Disease in Disadvantaged Populations. London: Elsevier Inc; 2017:357–365.
34. U.S. Department of Health and Human Services. Advancing American Kidney Health; 2019. Available at: https://aspe.hhs.gov/pdf-report/advancing-american-kidney-health. Accessed September 26, 2019.
35. U.S. Department of Health and Human Services. The Special Diabetes Program for Indians. Estimates of Medicare Savings 2019. Available at: https://aspe.hhs.gov/pdf-report/special-diabetes-program-indians-estimates-medicare-savings. Accessed September 26, 2019.
36. Morbidity and mortality of renal dialysis: an NIH consensus conference statement. Consensus Development Conference Panel. Ann Intern Med 1994;121:62–70.
37. Garcia-Garcia G, Martinez-Castellanos Y, Renoirte-Lopez K, et al. Multidisciplinary care for poor patients with chronic kidney disease in Mexico. Kidney Int Suppl (2011) 2013;3:178–183.
38. Stanifer JW, Von Isenburg M, Chertow GM, Anand S. Chronic kidney disease care models in low- and middle-income countries: a systematic review. BMJ Glob Health 2018;3:e000728.
39. Tapia-Conyer R, Gallardo-Rincon H, Betancourt-Cravioto M. Chronic kidney disease in disadvantaged populations: online educational programs for NCD prevention and treatment. In: Garcia-Garcia G, Agodoa LY, Norris KC, eds. Chronic Kidney Disease in Disadvantaged Populations. London: Elsevier, Inc; 2017:337–345.
40. Narva AS, Norton JM, Boulware LE. Educating patients about CKD: the path to self-management and patient-centered care. Clin J Am Soc Nephrol 2016;11:694–703.
41. Schatell D. Web-based kidney education: supporting patient self-management. Semin Dial 2013;26:154–158.
