Higher habitual protein intake is not linked to decline of iohexol-measured GFR in adults ≥40 years

Abstract Background High habitual dietary protein intake may increase glomerular workload and contribute to hyperfiltration, but the long-term renal effects in individuals without chronic kidney disease (CKD) remain debated. Prior population studies have relied on estimated glomerular filtration rate (eGFR), which may be biased by non-GFR determinants. We examined whether higher protein intake is associated with decline in kidney function using repeated measurements of iohexol-measured GFR (mGFR). Methods We analysed data from the Renal Iohexol Clearance Survey (RENIS), a population-based cohort with repeated mGFR measurements over follow-up (n=1,324). Baseline protein intake was estimated using a validated food-frequency questionnaire. Associations of protein intake with GFR decline rate, accelerated GFR decline (top 10% with the steepest annual reductions), and incident incident mGFR <60 mL/min/1.73 m² were assessed using linear mixed models, logistic regression, and interval-censored Cox regression. Results Mean age was 64 years, 50% were women, and mean baseline mGFR was 89 mL/min/1.73 m². Median follow-up was 10 years. Mean reported protein intake was 1.2 ± 0.5 g/kg/day, with the lowest quartile consuming <0.9 g/kg/day and the highest ≥1.4 g/kg/day. Protein intake was not associated with mGFR decline (−0.01 mL/min/1.73 m² per year [95% CI −0.04 to 0.02] per 0.1 g/kg/day higher protein intake). Protein intake was not associated with accelerated GFR decline or incident mGFR <60 mL/min/1.73 m². Conclusions Among middle-aged and older adults in the general population, higher estimated habitual protein intake was not associated with mGFR decline.