Distinguishing autoimmune recurrence from rejection in simultaneous pancreas-kidney transplantation recipients: a...

Simultaneous pancreas-kidney (SPK) transplantation provides durable glycemic control and survival benefit for selected patients with Type 1 diabetes and end-stage renal disease. Late-onset hyperglycemia after SPK is diagnostically challenging because pancreas graft dysfunction may reflect acute or chronic rejection, calcineurin inhibitor toxicity, vascular complications, post-transplant diabetes, or recurrent autoimmune type 1 diabetes (T1DR). Autoimmune recurrence occurs in a minority of recipients and is characterized by insulitis with selective beta-cell loss, often preceded by islet autoantibody conversion and progressive C-peptide decline. Distinguishing recurrence from rejection is clinically important because rejection may respond to intensified anti-rejection therapy, whereas established T1DR has no proven disease-modifying treatment. This case-based short review synthesizes current evidence on epidemiology, timing, maintenance immunosuppression, immunopathogenesis, genetic susceptibility, biomarkers, imaging, Banff-based histopathology, differential diagnosis, and management of recurrent autoimmune diabetes after SPK transplantation. A structured diagnostic approach integrating clinical timing, serology, metabolic testing, imaging, donor-specific antibody assessment, and pancreas biopsy with immunohistochemistry can help clinicians avoid both delayed recognition of recurrence and unnecessary escalation of immunosuppression.