Abstract Tacrolimus-induced thrombotic microangiopathy (TMA) is an uncommon but potentially reversible cause of renal allograft dysfunction and may occur in the absence of systemic manifestations. Here, we describe a case of a renal transplant recipient who developed acute graft dysfunction due to focal TMA and acute tubular injury without evidence of rejection or systemic hemolysis. Elevated tacrolimus trough levels and a high concentration-to-dose ratio prompted pharmacogenomic evaluation, which revealed a cytochrome P450 family 3 subfamily A member 5 *3/*3 poor metabolizer genotype. Renal biopsy demonstrated focal ischemic glomerular changes, arteriolar fibrin thrombi, and tubular injury, confirming tacrolimus toxicity. Reduction of tacrolimus dosage resulted in rapid improvement of renal function with sustained graft stability at 6 months. This case report highlights the critical role of early biopsy, therapeutic drug monitoring, and pharmacogenomic profiling in identifying localized tacrolimus-induced TMA and preventing irreversible graft injury.
Gupta et al. (Fri,) studied this question.