Protein intake and kidney function in the middle-age population: contrast between cross-sectional and longitudinal data

Background. Protein intake is considered a determinant of glomerular filtration rate (GFR). Urinary urea is an objective marker of protein intake. The population-based study investigated, cross-sectionally and longitudinally, the association of protein intake with GFR, indexed by estimated GFR (eGFR). Methods. Data were collected on overnight urinary urea, serum creatinine (S-cr), eGFR and other variables in 1522 men and women aged 45-64 years who participated in the Gubbio study (baseline). S-Cr, eGFR and other variables were re-assessed in 1144 of the 1425 survivors after 12-year follow-up. Results. At baseline, mean +/- SD was 84.0 +/- 11.4 mL/min x 1.73 m(2) for eGFR calculated by CKD-Epi equation and 1.34 +/- 0.57 g/day per kg of ideal weight for protein intake assessed by measurements of overnight urine excretion of urea nitrogen. Cross-sectional analyses of baseline data indicated a positive correlation of protein intake with eGFR (R = 0.180, P < 0.001). In multi-variable regression, 1 g/day higher protein intake related to 4.7 mL/min x 1.73 m(2) higher eGFR [95% confidence interval (CI) = 3.7/5.7]. At follow-up, mean +/- SD of 12-year eGFR change was -11.6 +/- 9.0 mL/min x 1.73 m(2). Baseline protein intake correlated with more negative eGFR change (R = -0.251, P < 0.001). In multi-variable regression, 1 g/day higher protein intake related to -4.1 mL/min x 1.73 m(2) more negative eGFR change (95% CI =-5.1/-3.1) and to 1.78 risk for incidence of eGFR < 60 mL/min x 1.73 m(2) (95% CI = 1.15/2.78). Conclusions. In middle-aged adults, high protein intake is associated cross-sectionally with higher GFR but longitudinally with greater GFR decline over time.