Diagnosis and Treatment of Acute Humoral Rejection After Kidney Transplantation: Preliminary Experience M. Crespo, M. Lozano, M. Sole, J. Mila, N. Esforzado, J. Martorell, and F. Oppenheimer ABSTRACT Background. Acute humoral rejection, or rejection associated with de novo production of anti-HLA donor-specific antibodies (DSA) after kidney transplantation (KTx), is a clinicopathologic entity that is not completely understood. Recent studies have proposed criteria for its diagnosis, including: (1) steroid-resistant acute dysfunction; (2) positive post-Tx donor-specific crossmatch (XM); and (3) widespread C4d deposits in peritubular capillaries (PTC) upon renal biopsy. Methods. During 2002, prospective screening for AHR was established at our unit, seeking DSA post-KTx in selected cases of steroid-resistant acute rejection or acute dysfunction in high-risk sensitized or re-Tx patients. Frozen donor lymphocytes were used for post-Tx flow cytometry (FC) XM and high-definition flow PRA for patients with no frozen donor cells. We treated patients diagnosed with DSA using plasma exchange and polyclonal immunoglobulin. Results. Post-Tx DSA studies were performed in 9 of 94 patients transplanted during 2002. We detected DSA post-Tx in 3 of 9 recipients: 2 by FCXM and 1 using high-definition flow PRA. Two were highly sensitized pre-Tx, but the third patient was a 70-year-old woman receiving a first Tx (PRA = 0%). All 3 recipients presented with severe steroid-resistant acute renal dysfunction during the first 2 weeks post-Tx. Biopsies showed some features of AHR (neutrophils in PTC); 1 case showed no signs of concomitant cellular rejection. All rejection episodes were treated successfully (XM became negative and renal function recovered) by combining plasma exchange and polyclonal immuno- globulin. Conclusions. The use of specific tools, like the crossmatch, in cases of acute, steroid- resistant renal graft dysfunction is important to identify and treat otherwise undetected humoral mechanisms of rejection. H UMORAL mechanisms of rejection were identified in the first human trials in kidney transplantation (KTx). In the 1960s the Tx community accepted that KTx should be performed only when the donor–recipient cross- match (XM) was negative. 1 The relevance of de novo humoral responses after KTx has gained much attention during the last few years. 2 Some groups have proposed diagnostic criteria for acute humoral rejection (AHR), including: steroid-resistant acute dysfunction, often resis- tant to antilymphocyte therapy; a positive donor-specific XM post-Tx; and the presence of C4d deposits in peritu- bular capillaries in the renal biopsy. 3,4 We used some of these criteria to identify AHR in our KTx population and to investigate specific treatment. PATIENTS AND METHODS During 2002, prospective screening for AHR was established at our unit. Immunologic high-risk patients with suspected acute rejection (AR) or non– high-risk patients with steroid-resistant AR were included in the present study. Frozen donor lymph-node lympho- cytes were stored at the time of Tx. Donor-specific XM after Tx From the Unidad de Trasplante Renal (M.C., N.E., F.O.), Unidad de Afe ´ resis (M.L.), and Departamento de Anatomia Patologica (M.S.), and Instituto Clinico de Infecciones e Inmu- nologia (ICII), (J.M., J.M.), Hospital Clinic, Barcelona, Spain. Address reprint requests to Marta Crespo Barrio, MD, Unidad de Trasplante Renal, Hospital Clinic, c/Villaroel 179, 08036 Barcelona, Spain. E-mail: crespo@clinic.ub.es © 2003 by Elsevier Inc. All rights reserved. 0041-1345/03/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/S0041-1345(03)00620-1 Transplantation Proceedings, 35, 1677–1678 (2003) 1677