Simultaneous pancreas and kidney transplant rejection: separate or synchronous events?

The results of simultaneous pancreas and kidney transplantation (SPK) cannot be matched by pancreas transplantation alone (PTA), in part because an independent diagnosis of pancreas graft rejection remains difficult. The relationship between rejection of the pancreas and rejection of the kidney is poorly understood, and it is not known whether simultaneous transplantation of both organs confers true protection to either graft. To study these questions, reliable canine allotransplant models of kidney transplantation alone (KTA), PTA, and SPK were established. Sixty-seven mongrel dogs received KTA (n=21), PTA (n=23), or SPK (n=23) with either no immunosuppression, low-dose cyclosporine (CsA)-based immunosuppression, or high-dose CsA-based immunosuppression. Needle core biopsy (NCB) and fine needle aspiration biopsy (FNAB) were performed at 0, 2, 4, 7, 9, 11, 14, 21, and 30 days or at the time of graft failure. Pancreas and kidney graft survival after SPK was significantly shorter in dogs given low-dose CsA than in dogs given high-dose CsA (pancreas, P<0.04; kidney, P<0.03). Concurrent NCBs and FNABs were performed on 227 occasions in pancreas grafts and 229 occasions in kidney grafts. The time to initial evidence of rejection by NCB was not different in any immunosuppressed group. Synchronous rejection occurred in 73% of immunosuppressed SPK biopsies. Kidney-only rejection occurred in 23% of biopsies and pancreas-only rejection occurred in only 3% after SPK. All markers of pancreas graft rejection were poor, with the most sensitive being NCB of the simultaneously transplanted kidney. In summary, recipients of SPK required more immunosuppression than recipients of PTA, and improved PTA survival should be achievable with more sensitive markers of rejection. Markers of kidney rejection were the most sensitive indicators of pancreas rejection, and independent pancreas rejection was uncommon after SPK.