Rescue Kidney Paired Donation as Emergency Salvage for Failed Desensitization

Kidney paired donation (KPD) and desensitization both have a role in live donor incompatible transplantation depending on immunological profile of the donor/recipient pair (1). Algorithms outlining options for incompatible patients highlight circumstances favoring KPD desensitization, or KPD-followed-by-desensitization (2). However, in situations where desensitization fails, options are limited and discontinuing plasmapheresis frequently results in antibody rebound. Here, we introduce the concept of “rescue” KPD as a novel approach for salvaging desensitization procedures that fail to achieve therapeutic goals (see Tables 1 and 2 for desensitization and antibody details, respectively).TABLE 1: Antibody data of failed desensitization cases versus original and rescue donorsTABLE 2: HLA type and DSA for each rescue KPD caseThe first patient, a 38-year old broadly sensitized African American gentleman, matched in a three-way KPD, with a donor for whom he was both human leukocyte antigen (HLA) and ABO incompatible. Plasmapheresis was successful in eliminating HLA antibody, but anti-A antibody rebounded between treatments and plasma replacement just before the planned transplant had a paradoxical effect, triggering a rise in isohemagglutinins. The day before transplantation, anti-A titers were 128 and well above our cutoff (≤ titer 16) for proceeding with transplantation. Plasmapheresis and immunosuppression were continued while the patient and his intended donor re-entered our KPD pool. A nondirected donor recently cleared for donation that was ABO and HLA compatible was identified 56 days after his original operation date and a simultaneous 3-way domino transplant was initiated. The recipient is 42 months posttransplantation with a creatinine of 1.8 mg/dL. The second patient, a 26-year old Asian woman, failed desensitization for a high titer positive cytotoxicity crossmatch with her donor. An earlier match run failed to identify a more favorable KPD opportunity. We reprofiled the patient and entered the pair back into our KPD pool. A newly registered pair was identified with a donor for whom the patient had a negative flow crossmatch (too pan-reactive to determine no absolute anti-HLA antibody) and a low titer blood group incompatibility. A two-way KPD kidney exchange was performed. The patient was discharged from hospital with creatinine of 0.5 mg/dL. Currently, 50 months posttransplant, the patient has slowly increasing creatinine and histological evidence of chronic transplant glomerulopathy and BK nephropathy. The third patient, a 51-year old man, was desensitized for a preemptive kidney transplant from his brother across a positive cytotoxic crossmatch (B-cell positive at titer of 128 and a negative T-cell crossmatch). After prolonged plasmapheresis therapy did not result in an abrogation of the cytotoxic crossmatch, the pair was placed back into our KPD pool while plasmapheresis was continued. A nondirected donor was identified with a favorable genotype and a domino-paired chain was initiated. He was discharged from hospital with creatinine of 1.0 mg/dL and is now 48 months posttransplant with a creatinine of 1.1 mg/dL. Before the advent of the concept of combining paired donation with desensitization and searching for the best donor genotype in a pool of incompatible pairs, we did perform many successful desensitization procedures when initial donor-specific antibodies(DSA) or isohemagglutinin titers were high between the recipient and their intended donor. We have shown that even patients with high strength positive cytotoxic crossmatches derive a significant survival benefit from desensitization and transplantation (3). The need for this has been largely obviated by the expansion of paired donation. However, some patients are both broadly sensitized and have high antibody strength against common antigens and for these patients there is tremendous competition for rare genotypes to find a low strength crossmatch. They tend to accumulate in the paired donation pool. If our patients remain unmatched for more than 1 year, we will accept a higher strength crossmatch and often it is with their original donor. In the three cases presented here, newly registered pairs or nondirected donors entered the pool after we began desensitization and by chance they had highly favorable donor genotypes making the rescue KPD possible. Although successful in our three cases, some may express concerns at committing patients to desensitization in the absence of suitable alternative donors and may prefer waiting. Entry into KPD pools is dynamic, and there will be instances in which desensitization is unsuccessful and a “look back” into the pool may facilitate successful transplantation. This is especially true because the strength of antibodies to unacceptable antigens is also dynamic and may change during the desensitization process. Thus, in the case of an unsuccessful attempt at desensitization, it would be of value in some cases to reprofile the patient's HLA antibody specificities and strength, using the postdesensitization serum to search for new favorable matches and nondirected donor genotypes. In rare circumstances (7 out of 211 cases) where desensitization has been undertaken but fails, effort should be made to facilitate transplantation by rescue KPD. Adnan Sharif Andrea A. Zachary Janet Hiller Dorry Segev Nada Alachkar Edward S. Kraus Niraj M. Desai Nabil N. Dagher Andrew L. Singer Robert A. Montgomery Renal Institute of Birmingham, Queen Elizabeth Hospital Birmingham, United Kingdom Department of Medicine, Johns Hopkins Medical Institutions Baltimore, MD Department of Surgery, Johns Hopkins Medical Institutions Baltimore, MD