Provenzano M, et al. - Researchers assessed the strength of association of proteinuria indexed to estimated glomerular filtration rate (GFR) [eGFR] with end-stage renal disease (ESRD) risk, vs absolute proteinuria (Uprot), in chronic kidney disease (CKD) patients of Stages G3–G5 referred to nephrology clinics. They found that filtration-adjusted proteinuria (F-Uprot) enabled prediction of ESRD at all stages of overt CKD. Also, compared with Uprot, it offered an improved reclassification of patients for renal risk, in particular, in more advanced and complicated disease.

Methods

• This is a multi-cohort prospective study.
• Participants were 3957 CKD patients of Stages G3–G5 referred to nephrology clinics.
• Researchers 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

• The study cohort had mean ± SD age 67 ± 14 years, comprised 60% males, diabetics 29%, cardiovascular disease (CVD) 34%, eGFR 32 ± 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.
• A total of 862 patients reached ESRD over a median follow-up of 44 months.
• At competing risk analysis, a progressive increase in ESRD risk was observed when F-Uprot was 1.0–4.9 and ≥5.0 vs <1.0 g/24 h per 100 mL/min/1.73 m² eGFR in Stages G3a–G4 (P < 0.001) and Stage G5 (P=0.002).
• In multivariable Cox analysis, ESRD in Stages G3a–G4 was predicted by Uprot while in G5 the impact was not significant; conversely, ESRD at all stages was significantly predicted by F-Uprot.
• According to Akaike information criterion, the F-Uprot model, vs the Uprot model, enabled a significantly better prediction.
• The observed 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.