Protein Intake and Kidney Function in the Population: Differences in Cross-Sectional and Longitudinal Data

Background: Protein intake is considered a determinant of glomerular ltration rate (GFR). Urinary urea (U-urea) is an objective marker of protein intake. This population-based study investigated cross-sectionally and longitudinally the association of U-urea as index of protein intake with GFR indexed by serum creatinine (S-cr) and estimated GFR (eGFR). Methods: Data were collected about overnight U-urea, S-cr, eGFR, and other variables in 1,522 men and women aged 45-64 year who participated in the Gubbio Study (baseline). Age, S-Cr, and eGFR were re-assessed after 12-year follow-up in 1,144 of the 1,425 surviving participants. Results: Mean±SD of U-urea was 17.0±7.1 mmol/h corresponding to an estimated daily protein intake of 71.5±29.8 g/d. U-urea associated inversely with S-cr and directly with eGFR in cross-sectional quartile analyses (P<0.001). In multi-variable cross-sectional regression, 7 mmol/h higher U-urea (approximately one SD of U-urea corresponding to 30 g/d higher protein intake) related to 0.026 mg/dL lower S-cr (95%CI= 0.020/0.032) and 2.56 mL/min higher eGFR (2.01/3.12). At follow-up, change over baseline was an increase for S-cr (+0.054±0.100 mg/dL) and a decrease for eGFR (-11.8±9.1 mL/min x 1.73 m2). Baseline U-urea associated directly with S-cr change and inversely with eGFR change in quartile analyses (P <0.001). In multi-variable regression, 7 mmol/h higher baseline U-urea related to 0.011 mg/dL more positive S-cr change (95%CI=0.006/0.016) and -0.07 mL/min more negative eGFR change per year (95%CI=-0.111/-0.038). Conclusions: In middle-aged adults, higher protein intake is associated crosssectionally with higher GFR but longitudinally with faster GFR decline over-time.