The Effect of Pravastatin on Acute Rejection After Kidney Transplantation-a Pilot Study1

Abstract

Hyperlipidemia is an important complication of kidney transplantation affecting up to 74% of recipients. HMG-CoA reductase inhibitors are reported to provide safe and effective treatment for this problem. A recent study suggests that pravastatin, an HMG-CoA reductase inhibitor, also decreases the incidence of both clinically severe acute rejection episodes and natural killer cell cytotoxicity after orthotopic heart transplantation. We have performed a prospective randomized pilot study of the effect of pravastatin on these same parameters after cadaveric kidney transplantation. Graft recipients were randomized to receive pravastatin after transplantation or no pravastatin (24 patients in each group) in addition to routine cyclosporine and prednisone immunosuppression. Lipid levels, acute rejection episodes and serial natural killer cell cytotoxicities were followed for 4 months after the transplant. At the end of the study period, pravastatin had successfully controlled mean total cholesterol levels (202.6 +/- 9.3 vs. 236.5 +/- 11.9 mg/dl, P < 0.02), LDL levels (107.9 +/- 6.6 vs.149.6 +/- 10.7 mg/dl, P < 0.002), and triglyceride levels (118.8 +/- 14.2 vs. 157.2 +/- 13.8 mg/dl, P < 0.05). In addition, the pravastatin-treated group experienced a reduction in the incidence of biopsy-proven acute rejection episodes (25% vs. 58%, P = 0.01), the incidence of multiple rejections episodes (P < 0.05), and the use of both pulse methylprednisolone (P = 0.01) and OKT3 (P = 0.02). Mean natural killer cell cytotoxicity was similarly reduced (11.3 +/- 1.6 vs. 20.0 +/- 2.0% lysis of K562 target cells, P < 0.002). These data suggest that pravastatin exerts an additional immunosuppressive effect in kidney transplant recipients treated with cyclosporine-based immunosuppression.

Normal Human Kidney HLA-DR–Expressing Renal Microvascular Endothelial Cells

“…We demonstrate that the HMG-CoA reductase inhibitor atorvastatin reduces ␥IFN-induced RMEC DR expression in vitro; however, our donor population did not allow us to answer the question of whether or not statins affect RMEC HLA-DR expression in vivo, because none of the donors were taking statins at the time of nephrectomy. Statins have been associated with a reduced rate of rejection in kidney transplants (49,50), although the mechanism for this effect has not been delineated. Although it is possible that statins may affect HLA class II expression on RMEC, the benefit of this under normal physiologic conditions depends on whether or not RMEC are capable of promoting an inflammatory response.…”

Reduced Incidence of New-Onset Diabetes Mellitus after Renal Transplantation with 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors (Statins)

“…Beneficial effects of statins specific to the transplant population that have been demonstrated previously include favorable effects on cardiac events (13), chronic and acute rejection (23,24), and associations with improved patient survival (25), lower blood pressure (26) and improved bone mineral density (27). In this study it has been demonstrated that statins have a favorable influence on the development of new-onset diabetes after transplantation as well.…”

Statins as antiinflammatory and immunomodulatory agents: A future in rheumatologic therapy?

“…Two small initial randomized controlled trials (RCTs) investigating statins for prevention of allograft kidney rejection showed significantly lower rejection rates in statin-treated patients (140,141). However, 3 subsequent RCTs demonstrated no significant differences between short-term rejection rates between 400 ABELES AND PILLINGER patients in the intervention and control arms (142)(143)(144).…”