Renal hyperfiltration increases CKD risk: A 5-year follow-up study of a working-age population

Background We previously reported that a rapid estimated glomerular filtration rate (eGFR) decline increases chronic kidney disease (CKD) risk, even among those with initially preserved kidney function, only in hypertensive individuals. This study aimed to determine whether renal hyperfiltration (RHF) increases future CKD risk in a working-age population and whether this association differs by hypertension status. Methods We analysed 14,539 employees (4,118 men, 10,421 women; aged 20–59) from corporate health check-ups (2011–2025) with ≥1-year follow-up. eGFR was calculated by sex using an equation incorporating age and serum creatinine. Participants had baseline eGFR ≥60 mL/min/1.73m², no proteinuria, no diabetes, and BMI <30 kg/m². RHF was defined as the top 5% of sex- and age-specific eGFR. To address reverse causality, those in the bottom 5% of eGFR were excluded; the remaining 13,789 participants (2,604 with hypertension [≥140/90 mmHg and/or medication], 11,185 without) were included in the present analysis. Cox proportional hazards models adjusted for sex, systolic blood pressure, and BMI estimated hazard ratios (HR) for CKD development (eGFR <45 mL/min/1.73m² and/or proteinuria). Results Over a 5-year follow-up, the overall CKD incidence was 3.17% (438/13,789): 5.16% in the RHF group and 3.07% in the non-RHF group. When stratified by hypertension status, incidence in the RHF vs. non-RHF groups was 4.60% vs. 2.82% for normotensive and 7.52% vs. 4.17% for hypertensive participants. The adjusted HRs (95% CI) for CKD associated with RHF were 1.64 [1.16–2.30, p=.005] overall, 1.58 [1.05–2.35, p=.026] in the normotensive group, and 1.92 [1.00–3.69, p=.049] in the hypertensive group. Conclusions In this working-age population, RHF increased CKD risk regardless of hypertension status. Notably, RHF is an early predictor of renal decline even among healthy individuals with both preserved kidney function and normal blood pressure. Key messages • A 5-year follow-up of over 13,000 workers demonstrated that renal hyperfiltration significantly increases the risk of CKD development, even in those with initially preserved renal function. • RHF is a known risk for renal failure in diabetes; however, early screening may also be essential in healthy working-age populations, as it predicts renal decline even in normotensive individuals.