*Purpose: Vascularized composite allotransplantation (VCA) has demonstrated impressive outcomes in areas of extremity (UETx), face (FTx), genitourinary, and abdominal wall transplantation with up to twenty years survival. While short-term risks of VCA have been quantified, longer-term consequences and strategies of management with respect to renal failure have not been reported

*Methods: Known VCA cases were reviewed with four cases (3 UETx, 1 FTx) of renal failure identified.

*Results: Patient 1 (UETx) with perioperative renal failure was converted from calcineurin (CNI) therapy to costimulatory blockade. Patient received living donor renal transplant at 7 months and is doing well 4 years. Patient 2 (FTx) demonstrated renal dysfunction by year 3. Attempted mTOR conversion resulted in moderate rejection, and peritoneal dialysis was initiated at year 6 and patient is listed for renal transplant. Patient 3 (UETx) on low-level CNI/prednisone demonstrated progressive renal dysfunction (GFR 20 mL/min/1.73m2) at year 8 but mild inflammation prevented immunosuppression conversion and renal transplant listing is pending. Patient 4 received bilateral hand transplant developed progressive renal dysfunction while on low-dose CNI therapy with good immunologic outcomes now being evaluated for renal transplant. VCA graft loss has been viewed as an unacceptable compromise once renal dysfunction has developed. Challenges include vascular access options, sensitization events from transfusions/transplant, limited access to living kidney donors, and compliance.

*Conclusions: Renal failure is an infrequent but predictable consequence of the CNI therapies required for good immunologic outcomes in VCA. Higher rejection risks for VCA limits consideration of alternate immunosuppressive therapies.

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