Progressive Allograft Dysfunction Leading to Rapid Graft Loss in a Kidney Transplant Recipient: A Multifactorial Case of Rejection, Drug Toxicity, and Unexpected Metabolic Injury

Introduction: In kidney transplant recipients, persistent allograft dysfunction may arise from an intricate interplay of immunologic, hemodynamic, pharmacologic, and metabolic factors. Early identification of the underlying cause is critical to optimizing management and improving long-term outcomes. Case Description: A 71-year-old African American male with ESRD due to type 2 diabetes mellitus underwent a living unrelateddonor kidney transplant. His medical history included Roux-en-Y gastric bypass surgery. Post-transplant, he developed episodes of acute tubular injury (ATN), borderline T-cell mediated rejection and tacrolimus toxicity, prompting conversion to belatacept. His graft failed at 15 months after he presented with worsening azotemia, progressive fluid overload and declining cardiac function. Kidney biopsy revealed ATN, mild interstitial inflammation (i1, t1), and advanced interstitial fibrosis (ci3). C4d staining was negative, without evidence of polyomavirus infection. MMDx was consistent with ATN. There were diffusepolarizable and non-polarizable microcalcifications highlighted by von Kossa stain consistent with allograft oxalosis. Discussion: This case illustrates the complexity of diagnosing progressive allograft dysfunction in the presence of multiple overlapping risk factors. Crucial for this graft loss was the finding of extensive and advanced oxalate nephropathy. Secondary oxalate nephropathy is an increasingly recognized but underappreciated cause of graft loss. Studies demonstrate that oxalate deposition can significantly impair both graft and patient survival, with early and late allograft dysfunction observed in affected patients. Mechanisms of injury include direct tubular toxicity, obstruction from crystal deposition, and promotion of interstitial fibrosis . In this case, both polarizable and non-polarizable microcalcifications were detected, consistent with mixed calcium oxalate and calcium phosphate crystal injury. Patients with prior Roux-en-Y gastric bypass are at particularly high risk for enteric hyperoxaluria, a key driver of systemic oxalate burden. This case emphasizes the importance of metabolic evaluation in transplant recipients with history of gastric bypass, beyond immunologic factors to optimize long-term graft survival.