Kidney health for everyone everywhere—from prevention to detection and equitable access to care

Abstract

Around 850 million people currently are affected by different types of kidney disorders.1International Society of Nephrology2019 United Nations High Level Meeting on UHC: Moving Together to Build Kidney Health worldwide; 2019.https://www.theisn.org/images/Advocacy_4_pager_2019_Final_WEB_pagebypage.pdfDate accessed: July 20, 2019Google Scholar 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 2040.2Foreman K.J. 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: 2052-2090Abstract Full Text Full Text PDF PubMed Scopus (465) Google Scholar 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.3Essue B.M. Laba T.L. Knaul F. et al.Economic burden of chronic ill health and injuries for households in low- and middle-income countries.in: Jamison D.T. Gelband H. Horton S. Disease Control Priorities Improving Health and Reducing Poverty. 3rd ed. World Bank, Washington, DC2018: 121-143Google Scholar 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.4Vanholder 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: 393-409Crossref PubMed Scopus (109) Google Scholar 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.4Vanholder 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: 393-409Crossref PubMed Scopus (109) Google Scholar, 5Luyckx V.A. Tuttle K.R. Garcia-Garcia G. et al.Reducing major risk factors for chronic kidney disease.Kidney Int Suppl (2011). 2017; 7: 71-87Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar, 6Luyckx V.A. Tonelli M. Stanifer J.W. The global burden of kidney disease and the sustainable development goals.Bull World Health Organ. 2018; 96: 414-422DCrossref PubMed Scopus (221) Google Scholar, 7Tonelli 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: 807-814Abstract Full Text Full Text PDF PubMed Scopus (470) Google Scholar, 8Kalantar-Zadeh K. Fouque D. Nutritional management of chronic kidney disease.N Engl J Med. 2017; 377: 1765-1776Crossref PubMed Scopus (213) Google Scholar 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.9United Nations General AssemblyPolitical declaration of the third high-level meeting of the General Assembly on the prevention and control ofnon-communicable diseases; 2018.https://www.un.org/ga/search/view_doc.asp?symbol=A/73/L.2&Lang=EDate accessed: November 3, 2019Google Scholar 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.4Vanholder 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: 393-409Crossref PubMed Scopus (109) Google Scholar, 5Luyckx V.A. Tuttle K.R. Garcia-Garcia G. et al.Reducing major risk factors for chronic kidney disease.Kidney Int Suppl (2011). 2017; 7: 71-87Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar, 6Luyckx V.A. Tonelli M. Stanifer J.W. The global burden of kidney disease and the sustainable development goals.Bull World Health Organ. 2018; 96: 414-422DCrossref PubMed Scopus (221) Google Scholar, 7Tonelli 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: 807-814Abstract Full Text Full Text PDF PubMed Scopus (470) Google Scholar 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. According to the expert definitions including the Center for Disease Control and Prevention,10Center for Disease Control and Prevention (CDC)Picture of America; 2017.At a Glance—Executive Summary. 2019; (Available at:)www.cdc.gov/pictureofamericaDate accessed: November 3, 2019Google Scholar 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.11Levey A.S. Schoolwerth A.C. Burrows N.R. et al.Centers for Disease Control and Prevention Expert PanelComprehensive 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: 522-535Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar 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.8Kalantar-Zadeh K. Fouque D. Nutritional management of chronic kidney disease.N Engl J Med. 2017; 377: 1765-1776Crossref PubMed Scopus (213) Google Scholar 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.Table 1Risk factors for de novo CKD as well as preexisting CKD progressionRisk factorContribution to de novo CKDContribution to CKD progressionNonmodifiable risk factorsAgeSeen with advancing age, especially in the setting of comorbid conditionsSome suggests that older patients with CKD may have slower progressionRace, genetics and other hereditary factors:•APOL1 gene•Hereditary nephritis (Alport’s)Common among those with African American ancestorsAcute GN•Postinfectious GN•Rapidly progressive GN<10%Recurrent GN or exacerbation of proteinuriaPolycystic kidney disorders<10%, family history of cystic kidney disordersAutoimmune disorders•Lupus erythematosus•Other connective tissue disorders (Sjogren’s syndrome)Congenital anomalies of the kidney and urinary tractMostly in children and young adultsMalignancy•Myeloma, light chain deposition disease, AL amyloidosis, and other plasma cell dyscrasias•LymphomaModifiable risk factorsGlycemic control in diabetes mellitusApproximately 50% of all CKDBlood pressure controlApproximately 25% of all CKDObesity10%–20%SmokingVia both nonhemodynamic and hemodynamic pathwaysAKI•ATN•Acute interstitial nephritisRepeated AKI bouts can cause CKDRepeated AKI bouts can accelerate CKD progressionPharmacologic•Medications causing interstitial nephritides (NSAIDs, chemotherapy, PPIs, etc.), ATN (aminoglycosides), renal ischemia and fibrosis (calcineurin inhibitors), crystal nephropathy (phosphate-based bowel preparations, trimethoprim-sulfamethoxazole)•Herbs and herbal medications•Contrast mediaVariable, e.g., in Taiwan, Chinese herb nephropathy (due to aristolochic acid) may be an important contributorEnvironmental•Heavy metal exposureRareAcquired or congenital solitary kidney•Cancer, donor or traumatic nephrectomy•Congenital solitary kidney, unilateral atrophic kidneyAcquired urinary tract disorders and obstructive nephropathyBenign prostatic hypertrophy and prostate cancer in menGynecologic cancers in womenNephrolithiasisInadequate fluid intake•Mesoamerican nephropathy•OthersUnknown risk, but high prevalence is suspected in Central AmericaWhereas in earlier CKD stages adequate hydration is important to avoid prerenal AKI bouts, higher fluid intake in more advanced CKD may increase the risk of hyponatremiaHigh protein intakeUnknown risk, recent data suggest higher CKD risk or faster CKD progression with high-protein diet, in particular, from animal sourcesHigher protein intake can accelerate the rate of CKD progressionCardiovascular risk factors and diseases (cardiorenal)•Heart failure•AtherosclerosisIschemic nephropathyLiver disease (hepatorenal)NASH cirrhosis, viral hepatitisEndocrine derangements•Testosterone and other androgen supplements•HypothyroidismAKI, acute kidney injury; AL, amyloid light-chain; ATN, acute tubular necrosis; CKD, chronic kidney disease; GN, glomerulonephritis; NASH, nonalcoholic steatohepatitis; NSAID, nonsteroidal anti-inflammatory drug; PPI, proton pump inhibitor.Many of these risk factors contribute to both de novo CKD and its faster progression and hence are relevant to both primary and secondary prevention. Open table in a new tab AKI, acute kidney injury; AL, amyloid light-chain; ATN, acute tubular necrosis; CKD, chronic kidney disease; GN, glomerulonephritis; NASH, nonalcoholic steatohepatitis; NSAID, nonsteroidal anti-inflammatory drug; PPI, proton pump inhibitor. Many of these risk factors contribute to both de novo CKD and its faster progression and hence are relevant to both primary and secondary prevention. 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.12Kovesdy C.P. Furth S.L. Zoccali C. World Kidney Day Steering CommitteeObesity and kidney disease: hidden consequences of the epidemic.J Ren Nutr. 2017; 27: 75-77Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar 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.13Tantisattamo E. Dafoe D.C. Reddy U.G. et al.Current management of acquired solitary kidney.Kidney Int Rep. 2019; 4: 1205-1218Abstract Full Text Full Text PDF Scopus (32) Google Scholar,14Webster A.C. Nagler E.V. Morton R.L. Masson P. Chronic kidney disease.Lancet. 2017; 389: 1238-1252Abstract Full Text Full Text PDF PubMed Scopus (996) Google Scholar Obesity should be avoided, and weight reduction strategies should be considered.12Kovesdy C.P. Furth S.L. Zoccali C. World Kidney Day Steering CommitteeObesity and kidney disease: hidden consequences of the epidemic.J Ren Nutr. 2017; 27: 75-77Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar 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.15Anand 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: 1254-1260Abstract Full Text Full Text PDF Scopus (11) Google Scholar 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 to the burden of this emerging disease suggests that among those with CKD, the have early of the disease, that is, CKD stages 1 and 2 with or CKD rate between and per A.C. Nagler E.V. Morton R.L. Masson P. Chronic kidney disease.Lancet. 2017; 389: 1238-1252Abstract Full Text Full Text PDF PubMed Scopus (996) Google Scholar these earlier stages of CKD, the main of kidney health education and for is to disease or hypertension is one of the most established risk factors for faster CKD The of the in secondary prevention is the protein to have a on L. Fouque D. The for protein in to in the management of J Kidney Dis. 2019; Full Text Full Text PDF Scopus Google Scholar data suggest that a new of medications as can CKD progression, but this may be related to glycemic of the C. et from the indicates may in preventing the progression of chronic kidney disease in patients with 2 diabetes of medications that Int. 2019; 96: Full Text Full Text PDF PubMed Scopus Google Scholar acute kidney injury may or may cause de novo CKD, acute kidney injury events that are on preexisting CKD may accelerate disease K. AKI lead to Nephrol. 2012; PubMed Scopus Google Scholar recent of secondary prevention that the of preventive strategies in CKD is the of a in polycystic kidney et in patients with polycystic kidney disease.N Engl J Med. 2012; PubMed Scopus Google Scholar In patients with advanced CKD, management of and related comorbid conditions such as and and cardiovascular disease is of high that these patients can to achieve of these patients renal therapy in the form of dialysis therapy or kidney a new is emerging to without dialysis by management of The of awareness of CKD around the world is one of the for of CKD in both and developing S. F. et and management of CKD and cardiovascular risk factors in health J Nephrol. PubMed Scopus Google Scholar, B. et on chronic kidney disease: Google Scholar, B. N. 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