W Lisik1, L Schoenberg, R E Lasky, B D Kahan. 1. Division of Immunology and Organ Transplantation, The University of Texas Medical School at Houston, Houston, Texas 77030, USA.
Abstract
BACKGROUND: Statins offer a strategy to address dyslipidemia commonly experienced by immunosuppressed transplant recipients. METHODS: This single-center, retrospective study of 325 recipients (mean posttransplant follow-up of over 6 years; 75.0+/-26.0 months) correlated four adverse outcomes-biopsy-confirmed acute rejection episodes, biopsy-confirmed chronic rejection/allograft nephropathy, graft loss, or death-with demographic and posttreatment variables. Patients were treated with a combination of sirolimus (SRL), cyclosporine (CsA), and various durations of steroids. Statins were prescribed for 259/325 (79%) recipients whose serum cholesterol exceeded 240 mg/dL and discontinued when the creatine phosphokinase increased fivefold (3.4%) or the liver function, threefold (3.0%) above normal. RESULTS: Upon univariate (hazard ratio [HR] 0.16; P<.001) and multivariate analysis (HR 0.38; P=.02), statins were markedly protective against acute rejection episodes. They reduced occurrence of chronic nephropathy/chronic rejection (HR 0.60; P=.03 and HR 0.52; P=.01, respectively). Incidences of graft loss were diminished (HR 0.26; P<.001 and HR 0.49; P=.01, respectively). Finally, the mortality rate was decreased (HR 0.21, P=.001 and HR 0.26, P=.01, respectively). Upon multivariate analysis, a reduced incidence of acute rejection was correlated with greater exposure to SRL (HR 0.78, P=.016) and CsA (HR 0.39; P=.006). CONCLUSIONS: This study demonstrated compelling effects of statins against all adverse outcomes among patients treated with SRL-based, CsA-containing regimens. The profoundly dyslipidemic properties of SRL may explain these unique findings compared with previous studies on patients treated with CsA-based regimens.
BACKGROUND: Statins offer a strategy to address dyslipidemia commonly experienced by immunosuppressed transplant recipients. METHODS: This single-center, retrospective study of 325 recipients (mean posttransplant follow-up of over 6 years; 75.0+/-26.0 months) correlated four adverse outcomes-biopsy-confirmed acute rejection episodes, biopsy-confirmed chronic rejection/allograft nephropathy, graft loss, or death-with demographic and posttreatment variables. Patients were treated with a combination of sirolimus (SRL), cyclosporine (CsA), and various durations of steroids. Statins were prescribed for 259/325 (79%) recipients whose serum cholesterol exceeded 240 mg/dL and discontinued when the creatine phosphokinase increased fivefold (3.4%) or the liver function, threefold (3.0%) above normal. RESULTS: Upon univariate (hazard ratio [HR] 0.16; P<.001) and multivariate analysis (HR 0.38; P=.02), statins were markedly protective against acute rejection episodes. They reduced occurrence of chronic nephropathy/chronic rejection (HR 0.60; P=.03 and HR 0.52; P=.01, respectively). Incidences of graft loss were diminished (HR 0.26; P<.001 and HR 0.49; P=.01, respectively). Finally, the mortality rate was decreased (HR 0.21, P=.001 and HR 0.26, P=.01, respectively). Upon multivariate analysis, a reduced incidence of acute rejection was correlated with greater exposure to SRL (HR 0.78, P=.016) and CsA (HR 0.39; P=.006). CONCLUSIONS: This study demonstrated compelling effects of statins against all adverse outcomes among patients treated with SRL-based, CsA-containing regimens. The profoundly dyslipidemic properties of SRL may explain these unique findings compared with previous studies on patients treated with CsA-based regimens.
Authors: Bing-Chen Liu; Xiang Song; Xiao-Yu Lu; Charles Z Fang; Shi-Peng Wei; Abdel A Alli; Douglas C Eaton; Bao-Zhong Shen; Xue-Qi Li; He-Ping Ma Journal: Am J Physiol Renal Physiol Date: 2013-05-29