International prevalence patterns of low eGFR in adults aged 18-60 without traditional risk factors from population-based cross-sectional studies: a disadvantaged populations eGFR epidemiology (DEGREE) study

Abstract The d isadvantaged populations eG F R (estimated glomerular filtration rate) e pid e miology (DEGREE) study was designed to gain insight into the burden of chronic kidney disease (CKD) of undetermined cause (CKDu) using standard protocols to estimate the general-population prevalence of low eGFR internationally. We estimated the age-standardised prevalence of eGFR<60ml/min/1.73m 2 in adults aged 18-60, excluding participants with commonly known causes of CKD, i.e., ACR>300mg/g or equivalent, or self-reported or measured hypertension or diabetes (eGFR<60 [absent HT,DM,high ACR] ), and stratified by sex and location. We included population-representative surveys conducted around the world that were either designed to estimate CKDu burden or were re-analyses of large surveys. There were 60 964 participants from 43 areas across 14 countries, with data collected during 2007-2023. The highest prevalence was seen in rural men in Uddanam, India (14%) and Northwest Nicaragua (14%). Prevalence above 5% was generally only observed in rural men, with exceptions for rural women in Ecuador (6%) and parts of Uddanam (6-8%), and for urban men in Leon, Nicaragua (7%). Outside of Central America and South Asia, prevalence was below 2%. These observations represent the first attempts to estimate the prevalence of eGFR<60 [absent HT,DM,high ACR] around the world, as an estimate of CKDu burden, and provide a starting point for global monitoring. It is not yet clear what drives the differences, but available evidence to date supports a high general-population burden of CKDu in multiple areas within Central America and South Asia, although the possibility that unidentified clusters of disease may exist elsewhere cannot be excluded. Lay summary In recent decades there have been reports of epidemics of chronic kidney disease (CKD) killing young men in Central America and South Asia. These cases do not involve the commonly known causes of CKD such as diabetes, so they are known as CKD of unknown cause (CKDu). To understand the size and extent of the problem around the world, we included data from studies that measured kidney function from 43 areas across 14 countries (60 964 people). We calculated the prevalence of poor kidney function in working-age men and women in urban and rural areas, in those without indicators of the commonly known causes of CKD. The most affected groups were rural men in Uddanam, India (14%), and Northwest Nicaragua (14%). Low prevalence (<2%) was seen in included areas outside of Central America and South Asia. These findings are important to direct future research, give clues to the possible causes of CKDu, and as a starting point for global monitoring.

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