Population-based dose-response curve of glomerular filtration rate to dietary protein intake

Massimo Cirillo, Fabiana Zingone, Cinzia Lombardi, Pierpaolo Cavallo, Alberto Zanchetti, Giancarlo Bilancio

Research output: Contribution to journalArticlepeer-review


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 (onU-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 onU-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 onU-ureaN decile indicated sigmoid curves of eGFR and S-cr over onU-ureaN with trend to flatness in the lowest 20% and the highest 20% of onU-ureaN (10.12 mg/h, respectively). Multi-variable spline regression indicated that the relation of eGFR over onU-ureaN was non-significant for onU-ureaN onU-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 onU-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 m2 between the lowest and highest 20% of onU-ureaN distribution. Conclusions Higher protein intake relates to higher eGFR. The relation is sigmoid with eGFR up-regulation for onU-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).

Original languageEnglish
Pages (from-to)1156-1162
Number of pages7
JournalNephrology Dialysis Transplantation
Issue number7
Publication statusPublished - Jul 1 2015


  • creatinine
  • dietary protein
  • eGFR
  • kidney function
  • urea

ASJC Scopus subject areas

  • Nephrology
  • Transplantation


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