CKD: A Call for an Age-Adapted Definition

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Abstract

Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m 2 . This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m 2 , whereas in elderly people it is increased at levels <45 ml/min per 1.73 m 2 . Therefore, we suggest that amending the CKD definition to include age-specific thresholds for GFR. The implications of an updated definition are far reaching. Having fewer healthy elderly individuals diagnosed with CKD could help reduce inappropriate care and its associated adverse effects. Global prevalence estimates for CKD would be substantially reduced. Also, using an age-specific threshold for younger persons might lead to earlier identification of CKD onset for such individuals, at a point when progressive kidney damage may still be preventable.

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Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis.

Caroline S. Fox, Kunihiro Matsushita, Mark Woodward … (2012)

Chronic kidney disease is characterised by low estimated glomerular filtration rate (eGFR) and high albuminuria, and is associated with adverse outcomes. Whether these risks are modified by diabetes is unknown. We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and end-stage renal disease (ESRD) associated with eGFR and albuminuria in individuals with and without diabetes. We analysed data for 1,024,977 participants (128,505 with diabetes) from 30 general population and high-risk cardiovascular cohorts and 13 chronic kidney disease cohorts. In the combined general population and high-risk cohorts with data for all-cause mortality, 75,306 deaths occurred during a mean follow-up of 8·5 years (SD 5·0). In the 23 studies with data for cardiovascular mortality, 21,237 deaths occurred from cardiovascular disease during a mean follow-up of 9·2 years (SD 4·9). In the general and high-risk cohorts, mortality risks were 1·2-1·9 times higher for participants with diabetes than for those without diabetes across the ranges of eGFR and albumin-to-creatinine ratio (ACR). With fixed eGFR and ACR reference points in the diabetes and no diabetes groups, HR of mortality outcomes according to lower eGFR and higher ACR were much the same in participants with and without diabetes (eg, for all-cause mortality at eGFR 45 mL/min per 1·73 m(2) [vs 95 mL/min per 1·73 m(2)], HR 1·35; 95% CI 1·18-1·55; vs 1·33; 1·19-1·48 and at ACR 30 mg/g [vs 5 mg/g], 1·50; 1·35-1·65 vs 1·52; 1·38-1·67). The overall interactions were not significant. We identified much the same findings for ESRD in the chronic kidney disease cohorts. Despite higher risks for mortality and ESRD in diabetes, the relative risks of these outcomes by eGFR and ACR are much the same irrespective of the presence or absence of diabetes, emphasising the importance of kidney disease as a predictor of clinical outcomes. US National Kidney Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.

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Analysis of the Global Burden of Disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016

Cheng-You Tsai, Tasheia Floyd, Geetha Maddukuri … (2018)

The last quarter century witnessed significant population growth, aging, and major changes in epidemiologic trends, which may have shaped the state of chronic kidney disease (CKD) epidemiology. Here, we used the Global Burden of Disease study data and methodologies to describe the change in burden of CKD from 1990 to 2016 involving incidence, prevalence, death, and disability-adjusted-life-years (DALYs). Globally, the incidence of CKD increased by 89% to 21,328,972 (uncertainty interval 19,100,079- 23,599,380), prevalence increased by 87% to 275,929,799 (uncertainty interval 252,442,316-300,414,224), death due to CKD increased by 98% to 1,186,561 (uncertainty interval 1,150,743-1,236,564), and DALYs increased by 62% to 35,032,384 (uncertainty interval 32,622,073-37,954,350). Measures of burden varied substantially by level of development and geography. Decomposition analyses showed that the increase in CKD DALYs was driven by population growth and aging. Globally and in most Global Burden of Disease study regions, age-standardized DALY rates decreased, except in High-income North America, Central Latin America, Oceania, Southern Sub-Saharan Africa, and Central Asia, where the increased burden of CKD due to diabetes and to a lesser extent CKD due to hypertension and other causes outpaced burden expected by demographic expansion. More of the CKD burden (63%) was in low and lower-middle-income countries. There was an inverse relationship between age-standardized CKD DALY rate and health care access and quality of care. Frontier analyses showed significant opportunities for improvement at all levels of the development spectrum. Thus, the global toll of CKD is significant, rising, and unevenly distributed; it is primarily driven by demographic expansion and in some regions a significant tide of diabetes. Opportunities exist to reduce CKD burden at all levels of development.

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Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts.

Ron T. Gansevoort, Kunihiro Matsushita, Marije van der Velde … (2011)

Both a low estimated glomerular filtration rate (eGFR) and albuminuria are known risk factors for end-stage renal disease (ESRD). To determine their joint contribution to ESRD and other kidney outcomes, we performed a meta-analysis of nine general population cohorts with 845,125 participants and an additional eight cohorts with 173,892 patients, the latter selected because of their high risk for chronic kidney disease (CKD). In the general population, the risk for ESRD was unrelated to eGFR at values between 75 and 105 ml/min per 1.73 m(2) but increased exponentially at lower levels. Hazard ratios for eGFRs averaging 60, 45, and 15 were 4, 29, and 454, respectively, compared with an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log ESRD risk without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 30, 300, and 1000 mg/g were 5, 13, and 28, respectively, compared with an albumin-to-creatinine ratio of 5. Albuminuria and eGFR were associated with ESRD, without evidence for multiplicative interaction. Similar associations were found for acute kidney injury and progressive CKD. In high-risk cohorts, the findings were generally comparable. Thus, lower eGFR and higher albuminuria are risk factors for ESRD, acute kidney injury and progressive CKD in both general and high-risk populations, independent of each other and of cardiovascular risk factors.