Background:
Findings that early changes in proteinuria independently predict long-term glomular filtration rate (gfr) decline (delta gfr) 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 delta gfr [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 delta gfr and, at multivariate analyses, independently predicted delta gfr (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 delta gfr (-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 delta gfrs. however, similar changes in proteinuria resulted in a difference in delta gfr (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/1.73 m2/month) in patients with basal proteinuria > or =3 g/24 hours as compared to those with basal proteinuria 1 to 3 g/24 hours (ramipril, 0.25 +/- 0.06 ml/min/1.73 m2/month; conventional therapy, 0.30 +/- 0.07 ml/min/1.73 m2/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.