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To investigate the efficacy of immunoadsorption (IA) in combination with tacrolimus (TAC) and mycophenolate mofetil (MMF) rescue therapy for C4d-positive acute humoral rejection (AHR) of renal transplants.Six of 185 cadaveric renal allograft recipients transplanted at our institute developed AHR over a mean period of 4.8 ± 0.8 d after operation. The ages ranged from 35 to 51 yr (mean 42.6 ± 5.6 yr). C4d deposits in peritubular capillaries (PTC) and accumulation of granulocytes in PTC were observed. IA with staphylococcal protein A and TAC–MMF combination therapy were given.After subjected to IA for 6.3 ± 1.03 sessions combined with TAC (0.14–0.16 mg/kg/d) and MMF (1.5 g/d) therapy, renal function recovered in all the patients. The mean duration of treatment when serum creatinine decreased was 14 ± 2.9 d. The pre-IA panel reactive antibody reactivity was as high as 50.2 ± 6.1%, and was significantly reduced to 8.3 ± 2.9% after IA. Repeated allograft kidney biopsy in four of six patients revealed a favorable remission of AHR. With a mean follow-up of 18.8 ± 5.46 months, patient and allograft survival are 100%, renal function remained stable with a mean serum creatinine of 1.2 ± 0.22 mg/dL.The optimal treatment for alloantibody-mediated AHR remains undefined. Our findings suggest that a therapeutic approach combining IA and TAC–MMF rescue has excellence to improve the outcome of AHR.