PLASMAPHERESIS AND INTRAVENOUS IMMUNE GLOBULIN PROVIDES EFFECTIVE RESCUE THERAPY FOR REFRACTORY HUMORAL REJECTION AND ALLOWS KIDNEYS TO BE SUCCESSFULLY TRANSPLANTED INTO CROSS-MATCH-POSITIVE RECIPIENTS

TLDR

Hyperacute and acute humoral rejection lack effective treatments and often cause graft loss, whereas plasmapheresis can remove HLA‑specific antibodies and intravenous gamma globulin can suppress alloantibody and modulate immune responses. The study tested whether combined plasmapheresis and IVIG could durably eliminate donor‑specific anti‑HLA antibodies to rescue patients with established AHR and preemptively desensitize cross‑match‑positive kidney transplant recipients. Seven patients were treated with sequential plasmapheresis and IVIG—three for established AHR and four preemptively—resulting in reversal of AHR and successful transplantation. All three rescued patients achieved graft survival, and all four preemptively treated patients received successful live‑donor transplants with an average creatinine of 1.4 mg/dL over a mean follow‑up of 58 weeks, demonstrating the protocol’s potential to eliminate donor‑specific antibodies and prevent hyperacute rejection.

Abstract

Hyperacute rejection (HAR) and acute humoral rejection (AHR) remain recalcitrant conditions without effective treatments, and usually result in graft loss. Plasmapheresis (PP) has been shown to remove HLA- specific antibody (Ab) in many different clinical settings. Intravenous gamma globulin (IVIG) has been used to suppress alloantibody and modulate immune responses. Our hypothesis was that a combination of PP and IVIG could effectively and durably remove donor-specific, anti-HLA antibody (Ab), rescuing patients with established AHR and preemptively desensitizing recipients who had positive crossmatches with a potential live donor.The study patients consisted of seven live donor kidney transplant recipients who experienced AHR and had donor-specific Ab (DSA) for one or more mismatched donor HLA antigens. The patients segregated into two groups: three patients were treated for established AHR (rescue group) and four cross-match-positive patients received therapy before transplantation (preemptive group).Using PP/IVIG we have successfully reversed established AHR in three patients. Four patients who were cross-match-positive (3 by flow cytometry and 1 by cytotoxic assay) and had DSA before treatment underwent successful renal transplantation utilizing their live donor. The overall mean creatinine for both treatment groups is 1.4+/-0.8 with a mean follow up of 58+/-40 weeks (range 17-116 weeks).In this study, we present seven patients for whom the combined therapies of PP/IVIG were successful in reversing AHR mediated by Ab specific for donor HLA antigens. Furthermore, this protocol shows promise for eliminating DSA preemptively among patients with low-titer positive antihuman globulin-enhanced, complement-dependent cytotoxicity (AHG-CDC) cross-matches, allowing the successful transplantation of these patients using a live donor without any cases of HAR.