Retarding progression of chronic renal disease: The neglected issue of residual proteinuria.

Findings that early changes in proteinuria independently predict long-term glomular filtration rate (GFR) decline (ΔGFR) would highlight proteinuria as a major determinant of progression in chronic renal disease.

We investigated whether percent changes (3 months vs. baseline) in proteinuria (adjusted for concomitant changes in GFR) and residual proteinuria at 3 months, predicted ΔGFR [over a median (IQ range) follow up of 31.3 (24.5 to 50.3) months] in 273 patients with proteinuric chronic nephropathies enrolled in the Ramipril Efficacy In Nephropathy (REIN) study.

Short-term changes and residual proteinuria (r = -0.23, P = 0.0001 for both) significantly correlated with ΔGFR and, at multivariate analyses, independently predicted ΔGFR (β = -0.23, P = 0.0002; β = -0.21, P = 0.0004, respectively). For comparable levels of residual proteinuria, patients with greater short-term reduction had slower ΔGFR (-0.28 ± 0.04 mL/min/1.73 m²/ vs. -0.53 ± 0.07 mL/min/1.73 m²/month, P = 0.04). On ramipril and conventional treatment, specular short-term changes in proteinuria (-18.2 ± 3.5% vs. 24.2 ± 6.7%, P < 0.0001, respectively) were associated with significantly different ΔGFRs. However, similar changes in proteinuria resulted in a difference in ΔGFR (ramipril, 0.39 ± 0.07 mL/min/1.73 m²/month; conventional therapy, 0.74 ± 0.11 mL/min/1.73 m²/month; P < 0.01) that was sevenfold higher (0.35 vs. 0.05 mL/min/1.73m²/month) in patients with basal proteinuria ≥3 g/24 hours as compared to those with basal proteinuria 1 to 3 g/24 hours (ramipril, 0.25 ± 0.06 mL/min/1.73m²/month; conventional therapy, 0.30 ± 0.07 mL/min/1.73m²/month; P = NS).

Regardless of blood pressure control and treatment randomization, short-term changes in proteinuria and residual proteinuria reliably predict long-term disease progression. Reducing proteinuria is renoprotective, particularly in nephrotic patients. As for arterial hypertension, proteinuria should be a specific target for renoprotective treatment.