Effects of sirolimus vs. calcineurin inhibitors on renal dysfunction after orthotopic liver transplantation

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Clinical Transplantation

Volume 21 Issue 3 Page 377 - May/June 2007

Clinical Transplantation 21 (3), 377–384. doi:10.1111/j.1399-0012.2006.00653.x

Effects of sirolimus vs. calcineurin inhibitors on renal dysfunction after orthotopic liver transplantation

Mical S. a,b,1aDivision of Gastroenterology, Penn Liver Transplant CenterbCenter for Clinical Epidemiology and Biostatistics1These authors contributed equally to this work., Jitha Raia,1aDivision of Gastroenterology, Penn Liver Transplant Center1These authors contributed equally to this work., Elliott KozinaaDivision of Gastroenterology, Penn Liver Transplant Center, Roy D. BloomccRenal-Electrolyte and Hypertension Division, Ground Gates, F. MarkmannddDepartment of Surgery, Penn Liver Transplant Center, Hospital of the University of Pennsylvania, Philadelphia, PA, USA, Kim M. OlthoffddDepartment of Surgery, Penn Liver Transplant Center, Hospital of the University of Pennsylvania, Philadelphia, PA, USA, Abraham ShakedddDepartment of Surgery, Penn Liver Transplant Center, Hospital of the University of Pennsylvania, Philadelphia, PA, USA and K. Rajender ReddyaaDivision of Gastroenterology, Penn Liver Transplant Center

aDivision of Gastroenterology, Penn Liver Transplant Center, bCenter for Clinical Epidemiology and Biostatistics, cRenal-Electrolyte and Hypertension Division, Ground Gates and dDepartment of Surgery, Penn Liver Transplant Center, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

K. Rajender Reddy, Professor of Medicine and Surgery, Director of Hepatology, Medical Director of Liver Transplantation, Liver Transplant Center, 2 Dulles, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104, USA. Tel.: +1 ; fax: +1 ;e-mail: rajender.reddy@...

1These authors contributed equally to this work.

MS, Rai J, Kozin E, Bloom RD, Markmann JF, Olthoff KM, Shaked A, Reddy KR. Effects of sirolimus vs. calcineurin inhibitors on renal dysfunction after orthotopic liver transplantation.Clin Transplant 2007: 21: 377–384. © Blackwell Munksgaard, 2007

Abstract

Abstract: Small uncontrolled series have suggested that sirolimus favorably impacts renal function after orthotopic liver transplantation (OLT). We sought to retrospectively compare renal dysfunction between cohorts exposed to sirolimus-based and calcineurin inhibitor-based immunosuppression. We retrospectively studied 79 patients converted to sirolimus-based immunosuppression and 100 control subjects continued on calcineurin inhibitor-based immunosuppression after OLT at our institution from 2000 to 2005. We collected clinical, demographic, and medication history. Renal dysfunction was defined as two or more wk of creatinine ≥2.0 mg/dL. Cohorts were compared using Kaplan–Meier survival analysis and proportional hazards modeling. Patients began sirolimus a median 83 d post-OLT and were followed on the medication for median 359 d. Patients in both the sirolimus and calcineurin inhibitor cohorts had median creatinine 1.2 mg/dL at study entry. Sirolimus-based immunosuppression was associated with a 1.8 (0.8–4.3, p = 0.17) hazards ratio for renal dysfunction. Adjusting for presence of hepatocellular carcinoma, combined kidney/liver transplantation, and age, the hazards ratio was 2.0 (0.8–4.8, p = 0.13). These point estimates were not substantially altered after subgroup analysis of sirolimus as the lone immunosuppressant, duration of exposure, and time between OLT and sirolimus conversion. In conclusion, our retrospective, controlled study showed that conversion to sirolimus after OLT did not protect against renal dysfunction. The effect of sirolimus on renal function will need to be prospectively evaluated in a prospective, randomized trial.