Effects of rosuvastatin on glomerular capillary size-selectivity function in rats with renal mass ablation.
BACKGROUND
Evidence is accumulating that statins can reduce proteinuria and disease progression in chronic kidney disease. However, some safety concerns have been recently raised on the use of these agents, mainly due to transient episodes of proteinuria observed in patients receiving high doses of rosuvastatin.


METHODS
We investigated in rats with renal mass ablation (RMR) whether rosuvastatin (5 or 20 mg/day) worsens proteinuria as compared to untreated RMR animals. Moreover, we also examined whether rosuvastatin-induced changes in proteinuria would be due to the effect of the drug on permselective properties of glomerular capillary barrier, measured by the fractional clearance of graded-size Ficoll molecules and/or by proximal tubular mechanisms, by assessing urinary excretion of beta(2)-microglobulin.


RESULTS
RMR rats given rosuvastatin for 28 days showed a progressive increase in proteinuria, with values numerically but not significantly higher than those in RMR animals given the vehicle. In RMR rats, rosuvastatin did not significantly affect the fractional clearance of Ficoll as compared to vehicle-treated RMR animals. A significant correlation was found between urinary protein and beta(2)-microglobulin excretion in rats treated with rosuvastatin (r = 0.936, p < 0.001), but not in those given vehicle. Renal function, glomerular and tubulointerstitial injury were comparable in rosuvastatin-treated and untreated RMR rats at the end of the 28-day follow-up.


CONCLUSIONS
In rats with RMR, rosuvastatin mildly enhances urinary protein excretion rate. This, however, was not the result of further changes in the size-permselective function of glomerular capillary barrier.
Corna
Daniela
D
Mario Negri Institute for Pharmacological Research, Ospedali Riuniti di Bergamo, Bergamo, Italy.
Sangalli
Fabio
F
Cattaneo
Dario
D
Carrara
Fabiola
F
Gaspari
Flavio
F
Remuzzi
Andrea
A
Zoja
Carla
C
Benigni
Ariela
A
Perico
Norberto
N
Remuzzi
Giuseppe
G
D000818:Animals; D002196:Capillaries / Q000187:drug effects* / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects*; D004195:Disease Models, Animal; D005464:Fluorobenzenes / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000187:drug effects; D011507:Proteinuria / Q000139:chemically induced / Q000503:physiopathology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium