EFFECT OF CYCLOSPORINE-A ON RENAL-FUNCTION AND KIDNEY GROWTH IN THE UNINEPHRECTOMIZED RAT

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 < 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 Mg/ml, P < 0.05), DNA (26.4 ± 1.7vs. 34.7 ± 2.1 μg/ml, P < 0.01), and protein content (6.4 ± 0.3 vs. 7.8 ± 0.2 mg/dl, P < 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 < 0.025 and 2.14 ± 0.14 vs. 1.63 ± 0.20 ml/min/100 g, P < 0.025, respectively). We conclude that the reduction in GFR associated with the chronic administration of CsA in the Ux rat can occur despite unchanged RPF, is reversible, and is ameliorated by renal denervation. The finding of reduced cortical RNA and DNA content in Ux rats treated with CsA indicate that both renal hypertrophy and hyperplasia may be obliterated with the chronic use of this drug.