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 (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).


CONCLUSIONS
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.
Ruggenenti
Piero
P
Mario Negri Institute for Pharmacological Research and Unit of Nephrology, Ospedali Riuniti, Azienda Ospedaliera, Bergamo, Italy. manuelap@marionegri.it
Perna
Annalisa
A
Remuzzi
Giuseppe
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011507:Proteinuria / Q000188:drug therapy* / Q000503:physiopathology*; D017257:Ramipril / Q000008:administration & dosage*; D012680:Sensitivity and Specificity
D000806:Angiotensin-Converting Enzyme Inhibitors; D017257:Ramipril