Burden of chronic kidney disease of unknown aetiology in South African urban and peri-urban settings: Findings from a community-based cross-sectional study

Chronic kidney disease of unknown aetiology (CKDu) has gained attention in several low- and middle-income countries, yet its epidemiological profile in Africa remains poorly characterised. In South Africa, many individuals with kidney impairment present without diabetes, hypertension, or other common risk factors, pointing to a potentially unrecognised burden of CKDu in the general population. The aim of the study was to estimate the prevalence of CKD and determine the proportion of cases attributable to unknown aetiology among adults in urban and peri-urban South African communities.

Participants aged 25–65 years included in this analysis were drawn from the South African Diabetes Prevention Programme, which is a study conducted in two provinces in South Africa, namely the Western Cape (urban community) and Eastern Cape (peri-urban community). Individuals identified as being at risk for type 2 diabetes (T2D) based on the African Diabetes Risk Score (a validated African non-laboratory screening tool comprising age, waist circumference and prevalent hypertension) in the original programme were included. This cross-sectional analysis enrolled adults from both urban (n=687) and peri-urban (n=224) communities, including those accessing primary healthcare facilities and surrounding residential areas. Data collection included structured questionnaires, anthropometric measurements, blood pressure assessment, and blood collection for biochemical analysis. Kidney function was estimated using the serum creatinine-based CKD Epidemiology Collaboration equation. Chronic kidney disease was defined as an estimated glomerular filtration rate of <60 ml/min/1.73m² and/or albumin-to-creatinine ratio (ACR) >3 mg/mmol. Individuals with kidney impairment and no evidence of T2D or hypertension were classified as presumptive CKDu.

Among the 911 participants included in this study, 81.7% were female, with a median age of 52 years. Of these participants, 9.9% had screen-detected T2D (based on an oral glucose tolerance test), 60.1% had hypertension, and 14.1% had CKD, with 1.3% presenting with all three conditions. Preliminary results show that 27.3% (n=35) of those with CKD met the criteria for CKDu. Of those with CKDu, the majority where in CKD stage 1 (71.4%), with 17.1% and 11.4% presenting with CKD stages 2 and 3, respectively. Most individuals with CKDu presented with albuminuria A2 (90.6%) (ACR: 3–30 mg/mmol), with 9.4% presenting with albuminuria A3 (>30 mg/mmol). Similar proportions of presumptive CKDu cases were identified amongst those residing in peri-urban and urban settlements (25.9% vs 27.7%, p=0.32). 

This study provides preliminary community-level evidence of CKDu prevalence in South Africa. A notable proportion of CKD cases occurs in the absence of T2D and hypertension, underscoring the need for improved surveillance, locally relevant diagnostic criteria, and research focussed on non-traditional factors. Although environmental, occupational, infectious, and cultural exposures, such as heat stress, informal employment, traditional medicine use, HIV infection, and environmental contaminants, have been suggested in the literature as potential contributors to CKDu, these were not assessed in this study and require systematic evaluation in future research.