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

11 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

ASJC Scopus subject areas

  • Nephrology

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