Desensitization in HLA-Incompatible Kidney Recipients and Survival

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1 T h e n e w e ngl a nd j o u r na l o f m e dic i n e original article Desensitization in HLA-Incompatible Kidney Recipients and Survival Robert A. Montgomery, M.D., D.Phil., Bonnie E. Lonze, M.D., Ph.D., Karen E. King, M.D., Edward S. Kraus, M.D., Lauren M. Kucirka, Sc.M., Jayme E. Locke, M.D., M.P.H., Daniel S. Warren, Ph.D., Christopher E. Simpkins, M.D., M.P.H., Nabil N. Dagher, M.D., Andrew L. Singer, M.D., Ph.D., Andrea A. Zachary, Ph.D., and Dorry L. Segev, M.D., Ph.D. A bs tr ac t From the Departments of Surgery (R.A.M., B.E.L., L.M.K., J.E.L., D.S.W., C.E.S., N.N.D., A.L.S., D.L.S.), Pathology (K.E.K.), and Medicine (E.S.K., A.A.Z.), Johns Hopkins Medical Institutions; and the Department of Epidemiology, Johns Hopkins University School of Public Health (L.M.K., D.L.S.) both in Baltimore. Address reprint requests to Dr. Montgomery at 720 Rutland Ave., Ross Research 765, Baltimore, MD 21205, or at rmonty@jhmi.edu. N Engl J Med 2011;365: Copyright 2011 Massachusetts Medical Society. Background More than 20,000 candidates for kidney transplantation in the United States are sensitized to HLA and may have a prolonged wait for a transplant, with a reduced transplantation rate and an increased rate of death. One solution is to perform livedonor renal transplantation after the depletion of donor-specific anti-hla antibodies. Whether such antibody depletion results in a survival benefit as compared with waiting for an HLA-compatible kidney is unknown. Methods We used a protocol that included plasmapheresis and the administration of low-dose intravenous immune globulin to desensitize 211 HLA-sensitized patients who subsequently underwent renal transplantation (treatment group). We compared rates of death between the group undergoing desensitization treatment and two carefully matched control groups of patients on a waiting list for kidney transplantation who continued to undergo dialysis (dialysis-only group) or who underwent either dialysis or HLA-compatible transplantation (dialysis-or-transplantation group). Results In the treatment group, Kaplan Meier estimates of patient survival were 90.6% at 1 year, 85.7% at 3 years, 80.6% at 5 years, and 80.6% at 8 years, as compared with rates of 91.1%, 67.2%, 51.5%, and.5%, respectively, for patients in the dialysisonly group and rates of 93.1%, 77.0%, 65.6%, and 49.1%, respectively, for patients in the dialysis-or-transplantation group (P<0.001 for both comparisons). Conclusions Live-donor transplantation after desensitization provided a significant survival benefit for patients with HLA sensitization, as compared with waiting for a compatible organ. By 8 years, this survival advantage more than doubled. These data provide evidence that desensitization protocols may help overcome incompatibility barriers in live-donor renal transplantation. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Charles T. Bauer Foundation.) 318

2 Renal-replacement therapy can be achieved by means of transplantation or dialysis. Transplantation offers clear benefits in terms of longevity, lifestyle, and savings in health care costs. 1-4 However, organs are scarce, and the rate of death among patients on the kidneytransplant waiting list is high. In 2008, of the 82,000 patients on the waiting list in the United States, 16,520 received a renal transplant, whereas 4800 died while waiting for one. 5 Patients who have become sensitized to HLA as a result of previous transplantation, pregnancy, or blood transfusion have an increased likelihood of a positive cross-match, indicating the presence of donorspecific anti-hla antibody. The presence of circulating donor-specific anti-hla antibody has been associated with hyperacute rejection, antibodymediated rejection, and unacceptably high rates of organ loss, and the presence of this antibody has historically been considered a contraindication to transplantation. 6-9 Many patients with such sensitization have a willing live donor but are unable to realize this benefit because of a positive cross-match. Among patients undergoing transplantation across HLA barriers, the use of preconditioning, either with high-dose intravenous immune globulin or with plasmapheresis plus low-dose intravenous immune globulin, has had promising shortterm outcomes, although rates of short-term and long-term antibody-mediated rejection have been high. -13 Crossing the HLA barrier is a relatively recent phenomenon, and data on long-term outcomes are limited In recent studies, rates of graft and patient survival in such cases have been well below national averages for compatible livedonor transplantation. 19 Although it is clear that desensitization increases transplantation rates and reduces the waiting time among patients with HLA sensitization, the inferior outcomes that have been reported to date raise the question of whether these patients would be better served by waiting for a compatible organ. Me thods Study Population From February 1998 through December 2009, a total of 211 patients underwent HLA-incompatible live-donor kidney transplantation, with HLA incompatibility defined by three non-overlapping categories of antibody strength: positive complement-dependent cytotoxic or flow-cytometric crossmatching or detectable donor-specific anti-hla antibody on multiplex bead assay (Luminex). All patients provided written informed consent to undergo plasmapheresis and the administration of albumin, fresh-frozen plasma, and intravenous immune globulin before transplantation. The consenting procedure included a description of possible adverse events. The patients were treated with a desensitization treatment protocol approved by the institutional review board at the Johns Hopkins Medical Institutions. Initially, the protocol was deemed to be innovative therapy, and a prospective clinical database was maintained. The board then granted approval to convert the clinical database to a research database, which undergoes annual review. The study protocol is available with the full text of this article at NEJM.org. Desensitization Treatment Plasmapheresis was performed with the use of a centrifuge-driven cell separator, as described previously. 20 After each plasmapheresis session, patients received intravenous cytomegalovirus immune globulin (Cytogam, CSL Behring) at a dose of 0 mg per kilogram of body weight. Escalating numbers of treatments were performed before and after transplantation on the basis of the level of donor-specific anti-hla antibody at baseline. 21 Briefly, patients with donor-specific anti- HLA antibody that was detected only by means of the bead assay and patients with a positive flowcytometric assay received between two and four treatments, depending on the initial level of the donor-specific anti-hla antibody and their response to the first two treatments. There was an increased range in the number of treatments before transplantation in the group with positive complement-dependent cytotoxicity cross-matches, which reflected the increased range in levels of cross-match reactivity. The goal of treatment was the conversion to a negative cytotoxic cross-match before transplantation. However, in a few cases, the strength of cross-matching for donor-specific anti-hla antibody plateaued at a low level of reactivity (titer, <8) on the complement-dependent cytotoxicity assay, and we proceeded with transplantation. We required a sustained reduction in the level of donor-specific anti-hla antibody in each patient before transplantation. Desensitization was attempted in 215 patients, and 211 underwent transplantation; the other 4 patients had 319

3 T h e n e w e ngl a nd j o u r na l o f m e dic i n e an inadequate response to plasmapheresis, which was defined as a complement-dependent cytotoxicity cross-match titer of 8 or more or a rebound in the level of donor-specific anti-hla antibody. Immunosuppression Mycophenolate mofetil (at a dose of 2 g per day) and tacrolimus (target serum level, 8 to 12 ng per milliliter) were administered with plasmapheresis before transplantation. Induction therapy consisted of the use of daclizumab, with an initial dose of 2 mg per kilogram and then 1 mg per kilogram every 2 weeks for a total of five doses, or antithymocyte globulin (Thymoglobulin, Genzyme) at a dose of 1.5 mg per kilogram per day for 5 days. Glucocorticoids, including dexamethasone, were administered at a dose of 0 mg intraoperatively and at a dose of 25 mg every 6 hours postoperatively for six doses, followed by tapering to 5 to mg daily during a 3-month period. Cross-Matching and Donor-Specific Anti-HLA Antibody Complement-dependent cytotoxicity assays and three-color flow-cytometric cross-matching were performed, as described previously. 22,23 Cytotoxicity assays were performed with antihuman globulin augmented for T cells and one wash for B cells, with a maximum titer of 512 for a positive result. Flow-cytometric cross-matching was performed with the use of the FACSCalibur flow cytometer (Becton Dickinson). The secondary antibody was an IgG heavy-chain specific mouse monoclonal antibody (BD Biosciences). Analyses to define antibody specificities were performed on the Luminex platform with the use of an HLA phenotype panel (Lifematch Class I and Class II ID, Gen-Probe) and a single-antigen panel (Single Antigen Beads, One Lambda). Results of bead assays were expressed as mean fluorescence intensity. Matched Control Subjects To determine whether desensitization provided a survival benefit, we performed a matched control analysis with deidentified patients drawn from the United Network for Organ Sharing (UNOS) kidneytransplant waiting list. For each patient in the group that underwent desensitization and transplantation (treatment group), on the date of the receipt of the incompatible transplant (with frameshifting to account for differences in follow-up between our patients and those in the national registry), we identified the five patients on the UNOS waiting list who were most closely matched. The percentage of panel-reactive antibodies was matched as follows: for patients with a panelreactive antibody level of 0% or 0%, a control subject with the same panel-reactive antibody level was identified; for patients with a level ranging from 98 to 99% or from 95 to 97%, a control subject with a level in the same range was identified; for patients with a level ranging from 85 to 94%, 65 to 84%, or 1 to 64%, a control subject with a panel-reactive antibody level within 2, 5, or points, respectively, of the antibody level in the study patient was identified. The remaining factors were matched with the use of iterative, expanding radius matching, as described previously, 24 in the following order of priority: age, blood type, number of previous transplantations, proportion of years of renal-replacement therapy with a functioning allograft, total number of years of renal replacement (including transplantation or dialysis), race, sex, and the presence or absence of diabetes. To determine whether the relatively small possibility of finding an HLA-compatible donor would affect the comparison with subjects on the waiting list, we divided the matched control subjects on the waiting list into two groups: those who continued to undergo dialysis (dialysis-only group) and those who either continued to undergo dialysis or underwent HLA-compatible transplantation at any time after the date of transplantation in the matched patient treated with desensitization (dialysis-ortransplantation group). Matched control subjects in the dialysis-only group were identified for all but one HLA-incompatible transplant recipient (a 46-year-old woman who had received a transplant in 1999, had a panel-reactive antibody level of 91%, and had undergone renal-replacement therapy for 28 years). Matching subjects in the dialysis-ortransplantation group were identified for all but three HLA-incompatible recipients. Statistical Analysis We used the Kaplan Meier method and the logrank test to compare rates of survival in the treatment group with those in the two matched control groups. Comparisons with the control groups were performed for both the overall group of HLAincompatible recipients and the three subgroups identified on the basis of the level of donor-specific anti-hla antibody. When survival curves for two 320

4 Table 1. Baseline Characteristics of HLA-Incompatible Kidney-Transplant Recipients, Stratified According to Strength of Donor-Specific Anti-HLA Antibody.* Characteristic All Patients (N = 211) Positive Results on Cross-Matching Assay CDC (N = 74) FCXM (N = 95) Multiplex Bead (N = 42) Age (yr) 44±13 44±14 46±12 42±14 Female sex (%) Race or ethnic group (%) White Black Hispanic Asian Other Blood-type incompatibility with donor (%) Calculated panel-reactive antibody (%) 82±23 90±15 80±27 73±24 Donor-specific anti-hla antibody (%) HLA class I HLA class II HLA class I and II Previous kidney transplants (%) Plasmapheresis sessions (no.) Before transplantation 4±4 6±5 3±2 3±4 After transplantation 5±4 8±6 4±3 5±3 * Plus minus values are means ±SD. Positive CDC denotes positive cross-matching on complement-dependent cytotoxicity assay, positive FCXM positive flow-cytometric cross-matching with negative CDC cross-matching, and positive multiplex bead positive bead crossmatching with negative FCXM. Race or ethnic group was self-reported. comparison populations crossed (i.e., when hazards were not proportional across time), the time at risk was divided into empirically (visually) derived intervals, and separate log-rank tests were performed within these strata. We used timedependent Cox models to test these inferences for sensitivity. All statistical analyses were performed with the use of Stata/MP, version R esult s Patients and Matched Control Subjects Of the 211 patients who underwent desensitization and transplantation, 66.8% were women; 78.2% were white, 13.7% were black, and 8.1% were of other racial or ethnic groups. More than half the patients (54.5%) had received at least one previous kidney transplant, and 14.7% had undergone at least two transplantations (Table 1). Patients had received renal-replacement therapy for a mean (±SD) of 8.8±7.7 years before desensitization. The average calculated cytotoxic panel-reactive antibody level was 82±23%, and 32.7% of patients had a level of 98% or more. For desensitization, patients were treated with a mean of 4±4 plasmapheresis sessions before transplantation and 5±4 sessions after transplantation. All patients received at least two plasma- 321

5 T h e n e w e ngl a nd j o u r na l o f m e dic i n e Table 2. Comparison of HLA-Incompatible Kidney-Transplant Recipients and Matched Control Subjects.* Characteristic HLA-Incompatible Recipients (N = 211) Matched Control Subjects Dialysis Only (N = ) Dialysis or Transplantation Therapy (N = 40) Age (yr) 44±13 45±12 46±12 Blood type (% of patients) O A B AB Female sex (% of patients) Black race (% of patients) Panel-reactive antibody level (%) 82±23 82±24 82±24 No. of previous transplants (% of patients) Years of renal-replacement therapy 8.8± ± ±6.8 Percent of years of renal-replacement therapy with ±33 29±35 28±31 a functioning allograft Diabetes (% of patients) * Plus minus values are means ±SD. The results of pairwise comparisons between HLA-incompatible recipients and either set of matched control subjects were not significant in any category. Renal-replacement therapy includes both dialysis and previous renal transplantation. pheresis sessions after transplantation, according to the protocol. Donor-specific anti-hla antibody was identified in all patients. Before the initiation of plasmapheresis, the specificities of donor-specific anti-hla antibody were as follows: class I only, 41.2%; class II only, 25.6%; and both class I and class II, 33.1%. Seventy-four patients had a positive cross-match on antihuman globulin enhanced cytotoxicity assay before desensitization, and 80.1% of patients had a positive cross-match on either flow cytometry or complement-dependent cytotoxicity assay. There were no significant differences in any of the matched variables between the treatment group and the two control groups (Table 2). Survival Benefit During the overall study period, desensitization was associated with a significant increase in the rate of patient survival, as compared with the rates in both the dialysis-only group and the dialysis-ortransplantation group (Fig. 1). In the treatment group, Kaplan Meier estimates of the rates of survival were 90.6% at 1 year, 85.7% at 3 years, 80.6% at 5 years, and 80.6% at 8 years, as compared with rates of 91.1%, 67.2%, 51.5%, and.5%, respectively, in the dialysis-only group and with rates of 93.1%, 77.0%, 65.6%, and 49.1%, respectively, in the dialysis-or-transplantation group (P<0.001 for both comparisons). However, at the end of the first year, there were no significant differences in the rates of survival among the three groups (P>0.20 for both comparisons). Survival Benefit and Cross-Match Strength A survival benefit was associated with desensitization in all preselected categories of donor-specific anti-hla antibody level. Patients with positive results on the bead assay (19.9% of the cohort) had the shortest follow-up, with a survival rate of 90.8% at 48 months in the treatment group, as compared with 57.4% for control subjects in the 322

6 dialysis-only group and 67.3% for those in the dialysis-or-transplantation group. Survival curves overlapped throughout the first 12 months for patients in the treatment group and all control subjects (P = 0.90 by the log-rank test). After 12 months, the rate of survival was higher in the treatment group than in both the dialysis-only group (P = 0.008) and the dialysis-or-transplantation group (P = 0.02) (Fig. 2A). Among patients in the treatment group who had a positive flow-cytometric cross-match (45.0% of the cohort), rates of survival were 92.0% at 1 year, 85.5% at 3 years, 79.7% at 5 years, and 79.7% at 8 years, as compared with rates of 90.3%, 67.1%, 53.2%, and 33.4%, respectively, in the dialysis-only group and rates of 92.2%, 75.4%, 64.8%, and 49.3%, respectively, in the dialysis-ortransplantation group. The survival curve in the treatment group crossed at 12 months with the curve for the dialysis-only group and at 18 months with the curve for the dialysis-or-transplantation group. During these months, the survival rate in the treatment group was similar to the rates in both the dialysis-only group (P = 0.75) and the dialysis-or-transplantation group (P = 0.85). Thereafter, survival rates were higher in the treatment group than in both the dialysis-only group (P<0.001) and the dialysis-or-transplantation group (P = 0.004) (Fig. 2B). Among patients in the treatment group who had positive cross-matches on the complementdependent cytotoxicity assay, survival rates were 87.7% at 1 year, 82.0% at 3 years, 78.0% at 5 years, and 78.0% at 8 years, as compared with rates of 92.2%, 67.0%, 49.7%, and 27.1%, respectively, in the dialysis-only group and with rates of 94.4%, 77.7%, 65.3%, and 44.6%, respectively, in the dialysis-or-transplantation group. The survival curves for the treatment group crossed at 18 months with the curve for the dialysis-only group and at months with the curve for the dialysis-or-transplantation group. During these months, survival rates in the treatment group were similar to those in the dialysis-only group (P = 0.62) and in the dialysis-or-transplantation group (P = 0.76). Thereafter, survival rates were higher in the treatment group than in both the dialysis-only group (P<0.001) and the dialysis-or-transplantation group (P = 0.004) (Fig. 2C). Survival (%) No. at Risk Desensitization treatment Dual therapy Desensitization treatment Dialysis or transplantation Months Adverse Events Table 3 shows the frequency of adverse events associated with desensitization treatment. The overall rate of minor reactions to plasmapheresis (rash, itching, flushing, tachycardia, headache, nausea, shortness of breath, paresthesias, and hypotension or hypertension) was.9%. Major events that were associated with plasmapheresis, including anaphylaxis with hypotension and airway edema, occurred in three patients (1.4%). Since plasmapheresis depletes coagulation factors, some of the bleeding complications may have been associated with the protocol. The rate of surgical-site bleeding that required a return to the operating room was 5.2%. Kidney biopsies in three patients (1.4%) were associated with bleeding that required reoperation, and graft loss occurred in one patient. Discussion In this study, we evaluated rates of survival after live-donor renal transplantation in 211 consecutive patients with donor-specific anti-hla antibody who underwent desensitization with a stan Figure 1. Survival Benefit of Desensitization in HLA-Incompatible Kidney Recipients. Kaplan Meier estimates of patient survival are shown for patients who underwent desensitization treatment before kidney transplantation (treatment group), as compared with two matched control groups of patients on a kidney waiting list who continued to receive dialysis (dialysis-only group) or who either continued to undergo dialysis or underwent HLA-compatible transplantation (dialysis-or-transplantation, or dual therapy, group). There were 35 deaths in the treatment group. The most common cause of death was cardiac disease (ischemic or valvular), which accounted for 15 deaths (43%). Infections, primarily opportunistic pneumonias, were responsible for 6 deaths (17%). The other causes of death were hemorrhage in 3 patients, bowel perforation or loss of vascular access in 2 patients each, and pancreatitis, cancer, motor vehicle accident, hypoglycemia, pulmonary embolism, pulmonary venous occlusion, and airway obstruction in 1 patient each

7 T h e n e w e ngl a nd j o u r na l o f m e dic i n e A Positive Multiplex Bead Assay, Negative Flow-Cytometric Assay 0 Desensitization treatment 90 Dialysis or transplantation Months Survival (%) No. at Risk Desensitization treatment Dual therapy B Positive Flow-Cytometric Assay, Negative Cytotoxic Cross-Match Survival (%) No. at Risk Desensitization treatment Dual therapy Desensitization treatment Dialysis or transplantation Months C Positive Cytotoxic Cross-Match Desensitization treatment 70 Dialysis or 60 transplantation Months Survival (%) No. at Risk Desensitization treatment Dual therapy Figure 2. Survival Benefit of Desensitization According to Strength of Cross-Matching for Donor-Specific Anti-HLA Antibody. Kaplan Meier survival estimates are shown for kidney recipients in the treatment group, as compared with the two matched control groups of patients on a kidney waiting list who continued to receive dialysis (dialysisonly group) or who either continued to undergo dialysis or underwent HLA-compatible transplantation (dialysisor-transplantation, or dual therapy, group), according to whether donor-specific anti-hla antibody was detected on the multiplex bead assay (Panel A), flow-cytometric assay (Panel B), or positive complement-dependent cytotoxicity assay (Panel C). dardized protocol that included plasmapheresis and the administration of low-dose intravenous immune globulin. During the 11-year study period, the patients had a significant survival benefit, as compared with matched control subjects who were on a kidney-transplant waiting list. Sensitization to HLA is a serious public health problem inasmuch as it is observed in % of patients on the kidney-transplant waiting list. Of these patients, 7908 are highly sensitized. 5 Despite being given priority in the current organallocation algorithm, highly sensitized patients (those with a panel-reactive antibody level >80%) have annual transplantation rates as low as 6.5%. 18 In a study by Vo et al., of 20 patients (80%) who underwent desensitization with intravenous immune globulin and anti-cd20 received a renal transplant within a mean of 12 months after treatment. In our study, 211 of 215 of patients (98%) who began treatment with plasmapheresis progressed to transplantation. Desensitization has the potential to greatly increase access to transplantation for this disproportionately disadvantaged population of candidates for transplantation and to increase their longevity. Concerns about the durability of allograft function, patient safety, and the financial burden on the health care system associated with desensitization protocols have persisted in the absence of studies reporting outcomes beyond 2 years. Data from studies to date have been difficult to interpret or compare because of heterogeneity among desensitization strategies, histocompatibility testing techniques, donor-specific anti-hla antibody levels, and demographic and clinical characteristics of donor and recipient populations. In our study, early rates of death after transplantation were higher than expected for live-donor transplantation, 25 per- 324

8 Table 3. Frequency of Adverse Events in 211 Patients during Desensitization Treatment.* Adverse Event Frequency no. of patients (%) Related to plasmapheresis Minor event 23 (.9) Major event 3 (1.4) Bleeding after biopsy 3 (1.4) Reoperation for bleeding 11 (5.2) * Minor events included rash, itching, flushing, tachycardia, headache, nausea, shortness of breath, paresthesias, and hypotension. Major events included anaphylaxis with hypotension and airway edema. haps in part reflecting the excess burden of coexisting illnesses associated with sensitization. As a result, direct comparisons of outcomes with those of compatible live-donor transplantations may be misleading. Notably, the baseline characteristics of our study patients were skewed toward high degrees of sensitization and prolonged periods of renal-replacement therapy. In our study, most of the adverse events associated with desensitization treatment were mild, but more serious reactions, including anaphylaxis and bleeding, did occur. In addition, there were six deaths from infection, and although a direct link to desensitization could not be established, such a connection merits further investigation. To determine the expected survival rate among patients with similar phenotypes on the waiting list, we identified two matched control groups: one in which patients continued to receive dialysis and one in which some of the patients receiving dialysis underwent transplantation of an HLA-compatible kidney during the study period. In the first 12 months, there was no significant difference in the survival rate between the treatment group and either control group. However, after the first year, the rate of survival in the treatment group was significantly higher. Furthermore, the survival benefit in the treatment group was preserved in all three subgroups defined on the basis of the donor-specific anti-hla antibody level. We and other investigators have identified an increase in the donor-specific anti-hla antibody level as an important predictor of reduced graft survival, and increased antibody levels require more intensive plasmapheresis before transplantation. 26 In our study, however, the rate of survival in the treatment group was superior to that in either matched control group, even among patients with the highest cross-match levels. For patients who have a willing but incompatible kidney donor, the alternative to desensitization is kidney paired donation, in which patients are entered into a pool and matching algorithms are used to identify compatible pairings. 27,28 On the surface, this would appear to be the least costly and most effective method for treating patients who have a positive cross-match with their donor, but since match rates for highly sensitized patients are very low, kidney paired donation is not a good solution for most sensitized patients. 4,29 Plasmapheresis does not result in a durable reduction in HLA antibody unless the patient undergoes transplantation within several days after the last treatment. This factor accounts for the paucity of reports of protocols that use plasmapheresis to desensitize patients who are on the waiting list for a transplant from a deceased donor. The implementation of this type of protocol would require that the patient receive some sort of special status to hasten the availability of an organ from a deceased donor. Studies of desensitization with the use of high-dose intravenous immune globulin in patients without live donors have shown increased rates of transplantation and good outcomes. 18 Our study has certain limitations. These include the single-center design and follow-up for less than 3 years for half the patients in the cohort. Thus, our findings will need to be confirmed in multicenter trials among nonreferral populations. With the elucidation of donor recipient phenotypes that will benefit the most from desensitization, long-term outcomes associated with the procedure are likely to improve. Also, earlier referral for desensitization treatment, which would result in fewer years of renal-replacement therapy, would be predicted to reduce mortality. Outcomes could be improved and costs could be lowered if patients were not required to have a completely negative cross-match for a kidney paired donation and if highly sensitized patients could be matched with a donor for whom HLA antibody cross-matching was weaker than that for their original donor. This study shows that sensitized patients, who have had limited access to transplantation for years, can derive a survival benefit from desensitization and receipt of a kidney transplant from a live donor. 325

9 Supported by a grant (RC1 DK086731) from the National Institute of Diabetes and Digestive and Kidney Diseases and by a grant from the Charles T. Bauer Foundation (to Drs. Montgomery, Warren, and Segev). Dr. Montgomery reports that his institution, John Hopkins University, has received grant support from Alexion, Genzyme, and Viropharma related to HLA-incompatible transplantation and that he has received lecture fees from educational grants to sponsoring academic institutions from Astellas and Genzyme; Dr. Zachary, receiving lecture fees from Genzyme and having an equity interest in Luminex; and Dr. Segev, receiving consulting and lecture fees from Genzyme. No other potential conflict of interest relevant to this article was reported. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank Vanessa Collins for providing data-management services and Julie Houp for her technical assistance with immunogenetics procedures. References 1. Port FK, Wolfe RA, Mauger EA, Berling DP, Jiang K. Comparison of survival probabilities for dialysis patients vs cadaveric renal transplant recipients. JAMA 1993;270: Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med 1999; 341: Lee AJ, Morgan CL, Conway P, Currie CJ. Characterisation and comparison of health-related quality of life for patients with renal failure. Curr Med Res Opin 2005; 21: Segev DL, Gentry SE, Warren DS, Reeb B, Montgomery RA. Kidney paired donation and optimizing the use of live donor organs. JAMA 2005;293: United Network for Organ Sharing home page. ( 6. Patel R, Terasaki PI. Significance of the positive crossmatch test in kidney transplantation. N Engl J Med 1969;280: Williams GM, DePlanque B, Lower R, Hume D. Antibodies and human transplant rejection. Ann Surg 1969;170: Starzl TE, Marchioro TL, Holmes JH, et al. Renal homografts in patients with major donor-recipient blood group incompatibilities. Surgery 1964;55: Lee PC, Terasaki PI, Takemoto SK, et al. All chronic rejection failures of kidney transplants were preceded by the development of HLA antibodies. Transplantation 2002;74: Glotz D, Antoine C, Julia P, et al. Desensitization and subsequent kidney transplantation of patients using intravenous immunoglobulins (IVIg). Am J Transplant 2002;2: Tyan DB, Li VA, Czer L, Trento A, Jordan SC. Intravenous immunoglobulin suppression of HLA alloantibody in highly sensitized transplant candidates and transplantation with a histoincompatible organ. Transplantation 1994;57: Montgomery RA, Zachary AA, Racusen LC, et al. 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. Transplantation 2000;70: Issa N, Cosio FG, Gloor JM, et al. Transplant glomerulopathy: risk and prognosis related to anti-human leukocyte antigen class II antibody levels. Transplantation 2008;86: Higgins RM, Bevan DJ, Carey BS, et al. Prevention of hyperacute rejection by removal of antibodies to HLA immediately before renal transplantation. Lancet 1996;348: Stegall MD, Gloor J, Winters JL, Moore SB, Degoey S. A comparison of plasmapheresis versus high-dose IVIG desensitization in renal allograft recipients with high levels of donor specific alloantibody. Am J Transplant 2006;6: Higgins R, Hathaway M, Lowe D, et al. Blood levels of donor-specific human leukocyte antigen antibodies after renal transplantation: resolution of rejection in the presence of circulating donor-specific antibody. Transplantation 2007;84: West-Thielke P, Herren H, Thielke J, et al. Results of positive cross-match transplantation in African American renal transplant recipients. Am J Transplant 2008;8: Vo AA, Lukovsky M, Toyoda M, et al. Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med 2008;359: Haririan A, Nogueira J, Kukuruga D, et al. Positive cross-match living donor kidney transplantation: longer-term outcomes. Am J Transplant 2009;9: Segev DL, Simpkins CE, Warren DS, et al. ABO incompatible high-titer renal transplantation without splenectomy or anti- CD20 treatment. Am J Transplant 2005; 5: Montgomery RA, Zachary AA. Transplanting patients with a positive donorspecific crossmatch: a single center s perspective. Pediatr Transplant 2004;8: Zachary AA, Montgomery RA, Ratner LE, et al. Specific and durable elimination of antibody to donor HLA antigens in renal-transplant patients. Transplantation 2003;76: Montgomery RA, Locke JE, King KE, et al. ABO incompatible renal transplantation: a paradigm ready for broad implementation. Transplantation 2009;87: Segev DL, Muzaale AD, Caffo BS, et al. Perioperative mortality and long-term survival following live kidney donation. JAMA 20;3: Organ Procurement and Transplantation Network. Scientific registry of transplant recipients. ( 26. Gloor JM, Winters JL, Cornell LD, et al. Baseline donor-specific antibody levels and outcomes in positive crossmatch kidney transplantation. Am J Transplant 20;: Montgomery RA, Zachary AA, Ratner LE, et al. Clinical results from transplanting incompatible live kidney donor/recipient pairs using kidney paired donation. JAMA 2005;294: Montgomery RA, Gentry SE, Marks WH, et al. Domino paired kidney donation: a strategy to make best use of live non-directed donation. Lancet 2006;368: Gentry SE, Segev DL, Montgomery RA. A comparison of populations served by kidney paired donation and list paired donation. Am J Transplant 2005;5: Montgomery RA. Renal transplantation across HLA and ABO antibody barriers: integrating paired donation into desensitization protocols. Am J Transplant 20;: Copyright 2011 Massachusetts Medical Society. 326

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