Reclassification of chronic kidney disease patients for end-stage renal disease risk by proteinuria indexed to estimated glomerular filtration rate: multicentre prospective study in nephrology clinics

Background. In non-dialysis chronic kidney disease (CKD), absolute proteinuria (Uprot) depends on the extent of kidney damage and residual glomerular filtration rate (GFR). We therefore evaluated, as compared with Uprot, the strength of association of proteinuria indexed to estimated GFR (eGFR) with end-stage renal disease (ESRD) risk. Methods. In a multi-cohort prospective study in 3957 CKD patients of Stages G3–G5 referred to nephrology clinics, we tested two multivariable Cox models for ESRD risk, with either Uprot (g/24 h) or filtration-adjusted proteinuria (F-Uprot) calculated as Uprot/eGFR 100. Results. Mean 6 SD age was 67 6 14 years, males 60%, diabetics 29%, cardiovascular disease (CVD) 34%, eGFR 326 13 mL/min/1.73 m2 , median (interquartile range) Uprot 0.41 (0.12–1.29) g/24 h and F-Uprot 1.41 (0.36–4.93) g/24 h per 100 mL/min/1.73 m2 eGFR. Over a median follow-up of 44 months, 862 patients reached ESRD. At competing risk analysis, ESRD risk progressively increased when F-Uprot was 1.0–4.9 and 5.0 versus <1.0 g/24 h per 100 mL/min/1.73 m2 eGFR in Stages G3a–G4 (P< 0.001) and Stage G5 (P ¼ 0.002).Multivariable Cox analysis showed that Uprot predicts ESRD in Stages G3a–G4 while in G5 the effect was not significant; conversely, F-Uprot significantly predicted ESRD at all stages. The F-Uprot model allowed a significantly better prediction versus the Uprot model according to Akaike information criterion. Net reclassification improvement was 12.2% (95% confidence interval 4.2–21.1), with higher reclassification in elderly, diabetes and CVD, as well as in diabetic nephropathy and glomerulonephritis, and in CKD Stages G4 and G5. Conclusions. In patients referred to nephrology clinics, F-Uprot predicts ESRD at all stages of overt CKD and improves, as compared with Uprot, reclassification of patients for renal risk, especially in more advanced and complicated disease.