Tacrolimus-Induced Thrombotic Microangiopathy Presenting Two Years After Live-Donor Kidney Transplant

Introduction: Tacrolimus-induced thrombotic microangiopathy (TI-TMA) is a rare but well-documented post-transplant complication, often associated with poor graft outcomes. We present a case of kidney transplant recipient who developed TI-TMA two years later with successful graft outcome after timely treatment. Case Description: 52-year-old woman with stage V CKD secondary to ADPKD underwent a live donor kidney transplant, maintained on prednisone, Envarsus XR, and mycophenolate with serum creatinine (sCr) 1 mg/dL and tacrolimus trough 6-8 ng/ml. Two years later, she presented with altered mental status. Labs showed sodium 114 mEq/L, bicarbonate 9 mEq/L, potassium 4.8 mEq/L, BUN 130 mg/dL, sCr 12 mg/dL, hemoglobin 6.9 g/dL, platelet count 66 x10 9 /L, LDH 550 IU/L, haptoglobin < 8 mg/dL, reticulocyte count 1.4%. Tacrolimus trough was elevated at 49 ng/mL. Lumbar puncture, complements (C3, C4) and ADAMTS13 were normal. Blood smear displayed schistocytes consistent with microangiopathic hemolytic anemia. Workup for DIC, Shiga-toxin HUS was negative. Allograft biopsy confirmed TMA (Fig 1). Due to worsening mental status and graft function, she required two dialysis sessions. Although aHUS was in the differential diagnosis, eculizumab was not initiated due to improving allograft function after switching from Envarsus to sirolimus. One year later, she had sCr of 1.5 mg/dL while on prednisone, sirolimus, and mycophenolate. Discussion: TI-TMA occurs in 1% of kidney transplant recipients, commonly diagnosed in the first-year post-transplant. Management includes tacrolimus discontinuation, plasmapheresis, and eculizumab. This case underscores the importance of considering TI-TMA as a potential cause of acute graft dysfunction beyond the early post-transplant period. Despite requiring dialysis, early recognition and modification of immunosuppression led to successful graft recovery.(A) Glomerulus with capillary thrombus. (PAS, 400x) (B) Blood vessel with red blood cell entrapped in vessel wall (H&E, 600x)