title: C4d-positive acute humoral renal allograft rejection: effective treatment by immunoadsorption.
abstract: There is increasing evidence for an important pathogenetic role of alloantibodies in acute renal allograft rejection. Acute humoral rejection (AHR) has been reported to be associated with a poor transplant survival. Although treatment modalities for cellular rejection are fairly well established, the optimal treatment for AHR remains undefined. Ten of 352 kidney allograft recipients transplanted at the authors' institution between November 1998 and September 2000 were diagnosed as having AHR, supported by severe graft dysfunction, C4d deposits in peritubular capillaries (PTC), and accumulation of granulocytes in PTC. AHR was diagnosed 18.9 +/- 17.5 d posttransplantation. All patients were subjected to immunoadsorption (IA) with protein A (median number of treatment sessions, 9; range, 3 to 17). Seven recipients with additional signs of cellular rejection (according to the Banff classification) received also antithymocyte globulin. In nine of ten patients, AHR was associated with an increase in panel reactive antibody reactivity. A pathogenetic role of alloantibodies was further supported by a positive posttransplant cytotoxic crossmatch in all tested recipients (n = 4). In nine of ten recipients, renal function recovered after initiation of anti-humoral therapy. One patient lost his graft shortly after initiation of specific therapy. Another recipient with partial reversal of AHR returned to dialysis 8 mo 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 of 14.2 +/- 7.1 mo (n = 8). In conclusion, this study suggests that AHR, characterized by severe graft dysfunction, C4d staining, and peritubular granulocytes, can be effectively treated by timely IA. In the majority of patients, IA treatment can restore excellent graft function over a prolonged time period.
authors.affiliation: Department of Internal Medicine III, University of Vienna, Vienna, Austria.
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhmig
authors.affiliation: Institute of Clinical Pathology, University of Vienna, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Regele
authors.affiliation: Department of Laboratory Medicine, University of Vienna, Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Exner
authors.affiliation: Department of Internal Medicine III, University of Vienna, Vienna, Austria.
authors.forename: Victor
authors.initials: V
authors.lastname: Derhartunian
authors.affiliation: Department of Internal Medicine III, University of Vienna, Vienna, Austria.
authors.forename: Josef
authors.initials: J
authors.lastname: Kletzmayr
authors.affiliation: Institute of Immunology, University of Vienna, Vienna, Austria.
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Säemann
authors.affiliation: Department of Internal Medicine III, University of Vienna, Vienna, Austria.
authors.forename: Walter H
authors.initials: WH
authors.lastname: Hörl
authors.affiliation: Department of Internal Medicine III, University of Vienna, Vienna, Austria.
authors.forename: Wilfred
authors.initials: W
authors.lastname: Druml
authors.affiliation: Department of Internal Medicine III, University of Vienna, Vienna, Austria.
authors.forename: Bruno
authors.initials: B
authors.lastname: Watschinger
mesh_terms: D000208:Acute Disease; D000328:Adult; D000917:Antibody Formation; D015704:CD4 Antigens / Q000032:analysis*; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000628:therapy*; D006650:Histocompatibility Testing; D006801:Humans; D007163:Immunosorbent Techniques; D007518:Isoantibodies / Q000276:immunology; D007668:Kidney / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D015704:CD4 Antigens; D007518:Isoantibodies