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

Daniel C. Batlle*, Cory Gutterman, Taha Keilani, Ramon Peces, Michael Lapointe

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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 < 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.

Original languageEnglish (US)
Pages (from-to)21-28
Number of pages8
JournalKidney international
Volume37
Issue number1
DOIs
StatePublished - Jan 1990

Funding

Parts of this work were presented at the Annual Meeting of the American Society of Nephrology, December 1986, and have been published in abstract form in Kidney International 31:454, 1987. This work was supported, in part, by a VA Merit Review Grant from Central Office. During the conduction of this work, Dr. Peces was a research fellow supported by a grant from the National Institute of Health of Spain (FISSS). Cyclosporin A used in this study was a gift from Dr. Winter, Sandoz Ltd., East Hanover, New Jersey, USA. The authors thank Dr. Yashpal Kanwar for his advice and assistance in the RNA and DNA measurements.

ASJC Scopus subject areas

  • Nephrology

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