The effects of lipid-lowering agents on acute renal allograft rejection.
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.


CONCLUSIONS
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.
Kasiske
B L
BL
Department of Medicine, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, MN 55415, USA.
Heim-Duthoy
K L
KL
Singer
G G
GG
Watschinger
B
B
Germain
M J
MJ
Bastani
B
B
D000328:Adult; D001219:Aspartate Aminotransferases / Q000097:blood; D002102:Cadaver; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D015248:Gemfibrozil / Q000627:therapeutic use*; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology* / Q000502:physiology; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D010919:Placebos; D019821:Simvastatin / Q000627:therapeutic use*; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D010919:Placebos; D014280:Triglycerides; D002784:Cholesterol; D019821:Simvastatin; D003404:Creatinine; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase; D015248:Gemfibrozil