title: Effects of sirolimus vs. calcineurin inhibitors on renal dysfunction after orthotopic liver transplantation.
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 > or =2.0 mg/dL. Cohorts were compared using Kaplan-Meier survival analysis and Cox 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.
authors.affiliation: Division of Gastroenterology, Penn Liver Transplant Center, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Mical S
authors.initials: MS
authors.lastname: Campbell
authors.forename: Jitha
authors.initials: J
authors.lastname: Rai
authors.forename: Elliott
authors.initials: E
authors.lastname: Kozin
authors.forename: Roy D
authors.initials: RD
authors.lastname: Bloom
authors.forename: James F
authors.initials: JF
authors.lastname: Markmann
authors.forename: Kim M
authors.initials: KM
authors.lastname: Olthoff
authors.forename: Abraham
authors.initials: A
authors.lastname: Shaked
authors.forename: K
authors.initials: K
authors.lastname: Rajender Reddy
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors; D006528:Carcinoma, Hepatocellular / Q000601:surgery; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects*; D016030:Kidney Transplantation; D016014:Linear Models; D008113:Liver Neoplasms / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D016016:Proportional Hazards Models; D051437:Renal Insufficiency / Q000139:chemically induced*; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D003404:Creatinine; D020123:Sirolimus