C4d-positive acute humoral renal allograft rejection: Effective treatment by immunoadsorption

There is increasing evidence for an important pathogenetic role of alloanti bodies in acute renal allograft rejection. Acute humoral rejection (AHR) ha s been reported to be associated with a poor transplant survival. Although treatment modalities for cellular rejection are fairly well established, th e optimal treatment for AHR remains undefined. Ten of 352 kidney allograft recipients transplanted at the authors' institution between November 1998 a nd September 2000 were diagnosed as having AHR, supported by severe graft d ysfunction, C4d deposits in peritubular capillaries (PTC), and accumulation of granulocytes in PTC. AHR was diagnosed 18.9 +/- 17.5 d posttransplantat ion. All patients were subjected to immunoadsorption (IA) with protein A (m edian number of treatment sessions, 9; range, 3 to 17). Seven recipients wi th additional signs of cellular rejection (according to the Banff classific ation) received also antithymocyte globulin. In nine of ten patients, AHR w as associated with an increase in panel reactive antibody reactivity. A pat hogenetic role of alloantibodies was further supported by a positive posttr ansplant cytotoxic crossmatch in all tested recipients (n = 4). In nine of ten recipients, renal function recovered after initiation of anti-humoral t herapy. One patient lost his graft shortly after initiation of specific the rapy. Another recipient with partial reversal of AHR returned to dialysis 8 rno after transplantation. Mean serum creatinine in functioning grafts was 2.2 +/- 1.2 mg/dl after the last IA session (n = 9) and 1.5 +/- 0.5 mg/dl after a follow-up or 14.2 +/- 7.1 ino (n = 8). In conclusion, this study su ggests that AHR, characterized by severe graft dysfunction, C4d staining, a nd peritubular granulocytes, can be effectively treated by timely IA. In th e majority of patients, IA treatment can restore excellent graft function o ver a prolonged time period.