DETERMINANTS OF KIDNEY HEALTH IN MULTI-ETHNIC ASIANS

Background: Chronic kidney disease (CKD) is a major and rising health and economic burden but remains poorly characterised in Asian populations. Ethnic disparities in kidney health are striking. In some reports, Malays experience over three-fold and Indians 1.2-fold higher rates of kidney failure compared with Chinese. The biological, socioeconomic, and behavioural determinants underlying differences in kidney health are incompletely understood.

Objectives: To elucidate ethnic differences in kidney health and the interaction of genetic, metabolic, and socioeconomic determinants across major Asian sub-populations.

Methods: We analysed data from the PRECISE-SG100K population cohort, a deeply phenotyped multi-ethnic cohort (n=46,325; 80.9% Chinese, 11.5% Malay, 7.6% Indian) integrating demographic, lifestyle, clinical, biochemical, genomic, and linked electronic-health-record data in Singapore. Kidney health was assessed by estimated glomerular filtration rate (eGFR) (as continuous variable and categorical variable, where low eGFR defined as less than 60 mL/min/1.73 m²). Multivariable linear, logistic, and Cox models examined associations between ethnicity and kidney outcomes adjusting for age, gender, metabolic risk factors, education, income, and smoking. Genome-wide association, gene-burden, and polygenic-risk-score (PRS) analyses complemented the phenotypic models.

Results: Mean eGFR was 94.7 ± 13.9 mL/min/1.73 m². After adjustment, eGFR was lower in Malays (–1.5 mL/min, p < 10⁻⁶) and Indians (–0.5 mL/min, p = 0.02) versus Chinese. Malays had 2.9-fold higher odds of low eGFR, while Indians showed a 1.2-odds, non-significant increase. Diabetes, hypertension, and obesity were the dominant risk factors, where prevalence and severity were substantially higher in Malays and Indians. HbA1c and BMI were markedly elevated compared with Chinese counterparts. Lower education and household income were independently associated with CKD (p < 0.001). Interaction analyses revealed that Malay ethnicity amplified the adverse impact of diabetes and hypertension on kidney function and CKD risk, indicating biologic or sociocultural effect modification. Notably, Malays exhibited lower eGFR even in the absence of conventional metabolic risks, suggesting background vulnerability from genetic or early-life factors. Genomic analyses identified 23 susceptibility loci for eGFR. PRS showed increased genetic susceptibility in ethnic minorities, decreased eGFR per quartile of PRS and increased odds of CKD, obesity and metabolic syndrome per standard deviation increased PRS. Electronic-health-record linkage (median follow-up 57 months) confirmed higher prevalent (adjusted OR=1.9) and incident CKD (HR =1.16) among Malays and Indians compared with Chinese. 

Conclusions: Kidney health varies significantly across Asian ethnicities. Malays and Indians display both greater exposure and greater biological susceptibility to metabolic and social determinants of CKD, on the background of increased genetic susceptibility. These findings highlight the need for ethnicity-tailored prevention, precision-risk stratification, and culturally adapted interventions. Integrating genomic, metabolic, and longitudinal health-data insights will be critical to uncover causal pathways, enable personalised approaches to disease prevention, and inform strategies for kidney-health equity.