Renal function in patients undergoing transplantation for... : Liver Transplantation (original) (raw)

Original Articles

Renal function in patients undergoing transplantation for nonalcoholic steatohepatitis cirrhosis: Time to reconsider immunosuppression regimens?

Houlihan, Diarmaid D.1,2,4; Armstrong, Matthew J.1,2,4; Davidov, Yana1,4,5; Hodson, James3; Nightingale, Peter3; Rowe, Ian A.1,4; Paris, Sue1,4; Gunson, Bridget K.1,4; Bramhall, Simon B.1,4; Mutimer, David J.1,4; Neuberger, James M.1,4; Newsome, Philip N.1,4

1Centre for Liver Research, National Institute for Health Research, University of Birmingham, Birmingham, United Kingdom

2Liver Biomedical Research Unit,, University of Birmingham, Birmingham, United Kingdom

3Department of Statistics, Wolfson Computer Laboratory, University of Birmingham, Birmingham, United Kingdom

4Liver Unit, Queen Elizabeth Hospital, University Hospital Birmingham, National Health Service Foundation Trust, Birmingham, United Kingdom

5Sheba Medical Center, Ramat Gan, Israel

Address reprint requests to Centre for Liver Research, National Institute for Health Research, and Liver Biomedical Research Unit, University of Birmingham, Birmingham, United Kingdom B15 2TT

Email: [email protected]

Received 8 April 2011; Accepted 8 July 2011

Diarmaid D. Houlihan and Ian A. Rowe are recipients of clinical research training fellowships from the Medical Research Council. Matthew J. Armstrong is the recipient of a clinical research training fellowship from the Wellcome Trust.

*These authors contributed equally to this work.

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Additional Supporting Information may be found in the online version of this article.

Abstract

Nonalcoholic fatty liver disease is an independent risk factor for chronic kidney injury (CKI), yet the impact of liver transplantation (LT) on renal function in this at-risk group is not known. We compared the post-LT renal function of patients with nonalcoholic steatohepatitis (NASH) and a matched comparison group. Forty-eight consecutive patients who underwent transplantation for NASH between 2000 and 2008 in a single UK center were compared to non-NASH patients who were matched by age, sex, Model for End-Stage Liver Disease score, and estimated glomerular filtration rate (eGFR; calculated with the Modification of Diet in Renal Disease formula). In comparison with non-NASH patients, NASH patients had a significantly lower eGFR 3 months after LT (eGFR difference = 8.85 mL/minute/1.73 m2, 95% confidence interval = 2.93-14.77). After adjustments for the effects of the body mass index, tacrolimus levels, diabetes mellitus, hypertension, and hepatocellular carcinoma, the difference between the groups remained significant 3 months after LT (P = 0.001). These data were then analyzed at numerous time points after LT (6, 12, and 24 months), and the time did not significantly affect the difference between the groups (P = 0.17). Within 2 years, 31.2% of the NASH patients (15/48) had developed stage IIIb CKI, whereas only 8.3% of the non-NASH patients (4/48) did (P = 0.009). In conclusion, this study has identified NASH as an independent risk factor for renal dysfunction after LT. Renal-sparing immunosuppression regimens should be considered at the time of LT to reduce the development of kidney injury in NASH patients. The optimization of such regimens requires a prospective study.

Abbreviations: BMI, body mass index; CKI, chronic kidney injury; CNI, calcineurin inhibitor; eGFR, estimated glomerular filtration rate; LT, liver transplantation; MDRD, Modification of Diet in Renal Disease; MELD, Model for End-Stage Liver Disease; MMF, mycophenolate mofetil; NA, not applicable; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis.