BACKGROUND: Preliminary results from clinical trials suggest that 3-hydroxy-3-methylglutarylco-enzyme A reductase inhibitors may help prevent acute renal allograft rejection. However, the mechanism for this putative effect of 3-hydroxy-3-methylglutarylco-enzyme A reductase inhibitors, and whether it is independent of lipid-lowering per SE are unknown. METHODS:Immediately after renal transplantation we randomly allocated (proportioned 2:1:2) patients to: 1) simvastatin (10 mg/day, n=53), 2) simvastatin placebo plus gemfibrozil (dose adjusted for renal function, n=36), and 3) simvastatin placebo (n=52). RESULTS:Simvastatin, but not gemfibrozil, reduced total and low density lipoprotein cholesterol during the first 90 days posttransplant. There were no major adverse effects of therapy. However, there were no effects of treatment on acute rejection. Indeed, survival free of acute rejection at 90 days was 72% in the simvastatin group, 72% in the gemfibrozil group, and 77% in the placebo control group (P=0.771). A post hoc power analysis suggested that there was only a 7.5% chance that a true effect of simvastatin on acute rejection (versus placebo) was not detected, and a 2.5% chance that an effect of gemfibrozil on acute rejection (versus placebo) was not detected in this study. CONCLUSION:Lipid-lowering agents may not reduce the incidence of acute renal allograft rejection. However, additional studies are needed to confirm this observation. In the mean time, many if not most renal transplant recipients should be treated with HMG-CoA reductase inhibitors starting early posttransplant to prevent cardiovascular disease complications. The results of this study suggest that starting lipid-lowering therapy immediately after renal transplantation is both safe and effective in lowering total and low density lipoprotein cholesterol.
RCT Entities:
BACKGROUND: Preliminary results from clinical trials suggest that 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors may help prevent acute renal allograft rejection. However, the mechanism for this putative effect of 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors, and whether it is independent of lipid-lowering per SE are unknown. METHODS: Immediately after renal transplantation we randomly allocated (proportioned 2:1:2) patients to: 1) simvastatin (10 mg/day, n=53), 2) simvastatin placebo plus gemfibrozil (dose adjusted for renal function, n=36), and 3) simvastatin placebo (n=52). RESULTS:Simvastatin, but not gemfibrozil, reduced total and low density lipoprotein cholesterol during the first 90 days posttransplant. There were no major adverse effects of therapy. However, there were no effects of treatment on acute rejection. Indeed, survival free of acute rejection at 90 days was 72% in the simvastatin group, 72% in the gemfibrozil group, and 77% in the placebo control group (P=0.771). A post hoc power analysis suggested that there was only a 7.5% chance that a true effect of simvastatin on acute rejection (versus placebo) was not detected, and a 2.5% chance that an effect of gemfibrozil on acute rejection (versus placebo) was not detected in this study. CONCLUSION:Lipid-lowering agents may not reduce the incidence of acute renal allograft rejection. However, additional studies are needed to confirm this observation. In the mean time, many if not most renal transplant recipients should be treated with HMG-CoA reductase inhibitors starting early posttransplant to prevent cardiovascular disease complications. The results of this study suggest that starting lipid-lowering therapy immediately after renal transplantation is both safe and effective in lowering total and low density lipoprotein cholesterol.
Authors: Franz Wiesbauer; Georg Heinze; Christa Mitterbauer; Franz Harnoncourt; Walter H Hörl; Rainer Oberbauer Journal: J Am Soc Nephrol Date: 2008-07-23 Impact factor: 10.121
Authors: K Sarat Chandra; Manish Bansal; Tiny Nair; S S Iyengar; Rajeev Gupta; Subhash C Manchanda; P P Mohanan; V Dayasagar Rao; C N Manjunath; J P S Sawhney; Nakul Sinha; A K Pancholia; Sundeep Mishra; Ravi R Kasliwal; Saumitra Kumar; Unni Krishnan; Sanjay Kalra; Anoop Misra; Usha Shrivastava; Seema Gulati Journal: Indian Heart J Date: 2014-12-24
Authors: Nizar Younas; Christine M Wu; Ron Shapiro; Jerry McCauley; James Johnston; Henkie Tan; Amit Basu; Heidi Schaefer; Cynthia Smetanka; Wolfgang C Winkelmayer; Mark Unruh Journal: BMC Nephrol Date: 2010-04-01 Impact factor: 2.388
Authors: Suetonia C Palmer; Jonathan C Craig; Sankar D Navaneethan; Marcello Tonelli; Fabio Pellegrini; Giovanni F M Strippoli Journal: Ann Intern Med Date: 2012-08-21 Impact factor: 25.391