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

Background. Findings that early changes in proteinuria independently predict long-term glomular filtration rate (GFR) decline (DeltaGFR) would highlight proteinuria as a major determinant of progression in chronic renal disease. Methods. We investigated whether percent changes (3 months vs. baseline) in proteinuria (adjusted for concomitant changes in GFR) and residual proteinuria at 3 months, predicted DeltaGFR [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. Results. Short-term changes and residual proteinuria (r=-0.23, P=0.0001 for both) significantly correlated with DeltaGFR and, at multivariate analyses, independently predicted DeltaGFR (beta=-0.23, P=0.0002; beta=-0.21, P=0.0004, respectively). For comparable levels of residual proteinuria, patients with greater short-term reduction had slower DeltaGFR (-0.28+/-0.04 mL/min/1.73 m(2)/vs. -0.53+/-0.07 mL/min/1.73 m(2)/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 DeltaGFRs. However, similar changes in proteinuria resulted in a difference in DeltaGFR (ramipril, 0.39+/-0.07 mL/min/1.73 m(2)/month; conventional therapy, 0.74+/-0.11 mL/min/1.73 m(2)/month; P<0.01) that was sevenfold higher (0.35 vs. 0.05 mL/min/1.73 m(2)/month) in patients with basal proteinuria greater than or equal to3 g/24 hours as compared to those with basal proteinuria 1 to 3 g/24 hours (ramipril, 0.25+/-0.06 mL/min/1.73 m(2)/month; conventional therapy, 0.30+/-0.07 mL/min/1.73 m(2)/month; P=NS). Conclusion. 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.