Population-based Dose-response Curve of Glomerular Filtration Rate to Dietary Protein Intake

Background: Kidney function measured as estimated glomerular filtration rate (eGFR) is a risk factor for mortality and severe diseases. Protein intake up-regulates kidney function. The dose-response curve of eGFR over protein intake is unknown. Urinary urea nitrogen is an objective index of protein intake.

Methods: The study cross-sectionally analysed the relation between overnight urinary urea nitrogen ((on)U-ureaN) and eGFR with and without control for other variables in 4106 adults of the Gubbio population. Analyses were done for serum creatinine (S-cr) also to investigate the independency of results from eGFR calculation.

Results: Higher (on)U-ureaN associated with higher eGFR, and lower S-cr independently of sex and age (simple and partial correlation coefficients >0.100, P < 0.001). Analyses by (on)U-ureaN decile indicated sigmoid curves of eGFR and S-cr over (on)U-ureaN with trend to flatness in the lowest 20% and the highest 20% of (on)U-ureaN (<5.19 and >10.12 mg/h, respectively). Multi-variable spline regression indicated that the relation of eGFR over (on)U-ureaN was non-significant for (on)U-ureaN <5.19 mg/h (coefficient = +0.27, 95% CI = -0.31/+0.84, P = 0.364), positive for (on)U-ureaN in the range 5.19-10.12 mg/h (coefficients = 1.35-1.64, lower 95% CI ≥ +0.48, P ≤ 0.002), and non-significant for (on)U-ureaN >10.12 mg/h (coefficient = +0.05, 95% CI = -0.06/ +0.16, P = 0.394). eGFR differed by ≈8 mL/min × 1.73 m(2) between the lowest and highest 20% of (on)U-ureaN distribution.

Conclusions: Higher protein intake relates to higher eGFR. The relation is sigmoid with eGFR up-regulation for (on)U-ureaN >5.19 mg/h, a threshold approximately corresponding to the recommended daily allowance for protein intake (0.8 g/day per kg of ideal weight).