Intensive Perioperative Simvastatin Treatment Protects from Chronic Kidney Allograft Injury

Abstract

Background/Aims: Ischemia-reperfusion injury (IRI) and innate immune response augment adaptive immunity and may also trigger repair processes that lead to uncontrolled fibrosis and atherosclerosis as seen in chronic allograft injury. Simvastatin has been shown to protect from renal IRI in several experimental studies. The aim of this study was to examine the effect of donor simvastatin pretreatment and early initiation of recipient simvastatin treatment on chronic kidney allograft injury. Methods: A rat renal transplantation model was used. Simvastatin was administered perorally for donor (5 mg/kg) and/or for recipient (2 mg/kg) 2 hours before transplantation and/or as daily treatment starting on the first postoperative day (2 mg/kg/day). The study included 5 groups: (1) no simvastatin, (2) donor pretreatment, (3) daily recipient treatment, (4) donor pretreatment + daily recipient treatment and (5) donor pretreatment + recipient pretreatment + daily recipient treatment. The grafts were recovered at day 90 for histopathological and immunohistochemical analysis. Kidney function was followed weekly with serum creatinine, and 24-hour urine protein was measured 60 and 90 days after transplantation. Results: We found that donor and recipient simvastatin pretreatment combined with daily recipient treatment reduced graft inflammation and chronic allograft injury. Treatment using only statins started after transplantation reduced inflammation to some extent, but did not affect chronic kidney allograft injury. Pretreatment using only donor statins impaired graft function and increased proteinuria. Conclusion: Our data suggest that perioperative recipient statin treatment reduces inflammation and may protect the graft in the long term.