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NDT Advance Access originally published online on November 14, 2006
Nephrology Dialysis Transplantation 2007 22(2):369-375; doi:10.1093/ndt/gfl631
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Telmisartan attenuates chronic ciclosporin A nephrotoxicity in a pig model

Donata Cibulskyte1,2, Michael Pedersen3, Arne Hørlyck4, Niels Marcussen5, Hans Erik Hansen1,2, Jørgen Frøkiær2,6, Melvin Madsen1,2 and Jens Mortensen2

1Department of Renal Medicine, 2Clinical Institute, 3MR Research Centre, 4Department of Radiology, Skejby Hospital, Aarhus University Hospital, 5Department of Pathology, Aarhus University Hospital and 6The Water and Salt Research Center, University of Aarhus, Aarhus, Denmark

Correspondence and offprint requests to: Jens Mortensen, Clinical Institute, Skejby Hospital, Aarhus University Hospital, 8200 Aarhus N, Denmark. Email: jmo{at}dadlnet.dk



  Abstract

Background. We have previously demonstrated renal enlargement in pigs treated with ciclosporin A (CsA) 10 mg/kg/day orally for 6 months. The aim of the study was to investigate the effect of oral CsA (10 mg/kg/day) for 12 months on kidney structure and function and the potential renoprotective role of angiotensin II (Ang II) receptor blocker telmisartan on chronic CsA nephrotoxicity in pigs.

Methods. Fourteen Göttingen minipigs aged 12–14 months were included: pigs received either CsA 10 mg/kg/day (n = 7) or CsA 10 mg/kg/day + telmisartan 40 mg/day (n = 7) orally for 12 months. At week 0, 12, 31, 38, 47 and 54, we measured body weight, mean arterial blood pressure (MAP), serum creatinine, whole blood trough CsA, plasma Ang II, haemoglobin and liver function parameters. Magnetic resonance imaging was used to estimate kidney length, volume, relative glomerular filtration rate (rGFR) and renal blood flow (RBF). Kidney tissue biopsies were used for conventional histological examination.

Results. Plasma Ang II levels were significantly higher during telmisartan treatment. Interstitial fibrosis and glomerulosclerosis occurred in both groups, but were attenuated in the telmisartan-treated pigs (P = 0.064). A significant increase in renal volume was seen in both groups, but tended to be lower in the CsA + telmisartan pigs at 54 weeks (P = 0.097). Telmisartan did not reduce MAP, RBF or rGFR.

Conclusions. Long-term CsA treatment causes histopathological changes in the porcine kidney similar to those observed in humans and results in renal enlargement. Telmisartan attenuates the CsA-induced histopathological changes and enlargement in the pig kidney.

Keywords: angiotensin II receptor blocker; ciclosporin A; nephrotoxicity; pig; renal enlargement; telmisartan


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[Abstract] [PDF]


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