Significance of CYP3A5 gene ^*1 allele and obese sarcopenia in renal transplant patients with nephrotoxicity while taking tacrolimus extended-release formulation

Abstract

In recent reports, graft survival was decreased after renal transplantation in transplant recipients due to their sarcopenia and frailty. In the present study, we experienced a case of obese sarcopenia, which showed conflicting results of renal biopsy and estimated effect by low trough concentration of tacrolimus, an immunosuppressive drug. The recipient was an obese male in his 30s with cytochrome p450 3A5 (CYP3A5)^*1/^*3 and ^*1 allele who was on hemodialysis. He received a renal transplant from a healthy female donor in her 60s, and was on tacrolimus to prevent rejection. The trough value of tacrolimus did not exceed 10 ng/mL; therefore, we suspected possible chronic antibody-related rejection based on serum creatinine and other factors. We performed a renal biopsy and measured the area under the concentration-time curve (AUC) of tacrolimus. As a result, tacrolimus-induced nephrotoxicity was suspected. In this case, the trough value of tacrolimus was low, but the AUC was high enough for renal toxicity. This high AUC could be caused by obese sarcopenia and the CYP3A5 wild type ^*1 allele. In the case of suspected obese sarcopenia, it would be preferable to measure body composition and to evaluate CYP3A5 gene polymorphism; if the trough level of tacrolimus is low in obese sarcopenic patients, addition of another alternative immunosuppressive drug may prevent post-transplant rejection without nephrotoxicity.