Effect of cyclosporin A on renal function and kidney growth in the uninephrectomized rat

Abstract

This study was designed to characterize the effect of cyclosporin A (CsA) on renal function and compensatory kidney growth in a rat model of uninephrectomy (Ux). The infusion of CsA (12.5 mg/k body wt) after acute Ux resulted in a fall in glomerular filtration rate (GFR) and renal plasma flow (RPF) and a marked increase in renal vascular resistance (RVR). Three weeks following Ux, GFR was also reduced in CsA treated animals as compared to pair-fed controls (0.39 +/- 0.03 vs. 0.67 +/- 0.06 ml/min/100 g, P less than 0.001), but RPF was not (1.97 +/- 0.14 vs 2.19 +/- 0.34 ml/min/100 g). The reduction in GFR seen in rats treated with CsA was fully reversible two weeks after discontinuation of the drug. Three weeks after Ux, kidney weight in CsA-treated animals increased to the level of pair-fed controls (1.50 +/- 0.05 vs. 1.57 +/- 0.06 g) but renal cortical RNA (39.4 +/- 4.3 vs. 49.3 +/- 1.3 micrograms/ml, P less than 0.05), DNA (26.4 +/- 1.7 vs. 34.7 +/- 2.1 micrograms/ml, P less than 0.01), and protein content (6.4 +/- 0.3 vs. 7.8 +/- 0.2 mg/dl, P less than 0.001) were all markedly reduced. Unilateral renal denervation in CsA-treated rats resulted in an increase in GFR and RPF as compared to that of pair-fed sham-denervated animals also treated with CsA (0.57 +/- 0.06 vs. 0.39 +/- 0.03 ml/min/100 g, P less than 0.025 and 2.14 +/- 0.14 vs. 1.63 +/- 0.20 ml/min/100 g, P less than 0.025, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)