The effect of aldosterone antagonist in experimental nephropathy induced by cyclosporine A.
This study evaluated the effect of spironolactone in the renal function alterations induced by cyclosporine A (CsA) in rats.


METHODS
Male Wistar rats fed with an unrestricted sodium diet received CsA 15 mg/kg/day or CsA at the same dosage plus 20 mg/kg/day of spironolactone. Another group received only saline. The animals that had proteinuria > 50 mg/24h or serum creatinine > 1.0 mg% were excluded, and after five weeks, the remaining rats were analyzed again for these parameters. At the end of the fifth week, these animals were also sacrificed, and their kidneys were analyzed histologically.


RESULTS
The animals that received CsA isolated or in association with spironolactone presented increase in serum creatinine. However, the comparison of the relative variation [Delta% = ([final - initial] / initial) x 100] of the serum creatinine concentrations in the beginning and at the end of the experiment among the animal groups showed a significant increase in the CsA group compared with the saline group (44.17 +/- 30.7% vs. -6.19 +/- 14.5%; p = 0.005), whereas there was no difference between the CsA + spironolactone and the saline group. In all of the animal groups, the values of 24-hour proteinuria were similar at the end of the experiment, and no renal histological alterations were observed.


CONCLUSIONS
This experimental model of nephrotoxicity by CsA in rats without salt restriction in the diet showed that CsA reduced the glomerular filtration and suggested that the blockage of aldosterone receptors prevented, at least partially, the reduction in renal function induced by CsA.
Santa Casa de São Paulo School of Medicine, São Paulo, Brazil.
Felipe Machado
FM
Silva
Luiz Antonio
LA
Miorin
Yvoty Alves dos Santos
YA
Sens
D000818:Animals; D003404:Creatinine / Q000097:blood*; D016572:Cyclosporine / Q000494:pharmacology; D004195:Disease Models, Animal; D018450:Disease Progression; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects* / Q000494:pharmacology; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D011336:Probability; D011507:Proteinuria; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013148:Spironolactone / Q000494:pharmacology*; D018709:Statistics, Nonparametric
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D016572:Cyclosporine; D003404:Creatinine