Donor Kidney Exchanges

Kidney transplantation from live donors achieves an excellent outcome regardless of human leukocyte antigen (HLA) mismatch. This development has expanded the opportunity of kidney transplantation from unrelated live donors. Nevertheless, the hazard of hyperacute rejection has usually precluded the transplantation of a kidney from a live donor to a potential recipient who is incompatible by ABO blood type or HLA antibody crossmatch reactivity. Region 1 of the United Network for Organ Sharing (UNOS) has devised an alternative system of kidney transplantation that would enable either a simultaneous exchange between live donors (a paired exchange), or a live donor/deceased donor exchange to incompatible recipients who are waiting on the list (a live donor/list exchange). This Regional system of exchange has derived the benefit of live donation, avoided the risk of ABO or crossmatch incompatibility, and yielded an additional donor source for patients awaiting a deceased donor kidney. Despite the initial disadvantage to the list of patients awaiting an O blood type kidney, as every paired exchange transplant removes a patient from the waiting list, it also avoids the incompatible recipient from eventually having to go on the list. Thus, this approach also increases access to deceased donor kidneys for the remaining candidates on the list.     

Unintended Consequences of the New National Kidney Allocation Policy in the United States

The new national Kidney Allocation System of the Organ Procurement and Transplantation Network (OPTN), effective as of December 4, 2014, was designed to improve the chances of transplanting the most highly sensitized patients on the waitlist, those with calculated panel reactive antibody values of 98%, 99% and 100%. Recently, it was suggested that these highly sensitized patients will experience inequitable access, given the reported high prevalence of antibodies to HLA‐DP, and the fact that only about 1/3 of deceased donors are typed for HLA‐DP antigens. Here we report that 320/2948 flow cytometric crossmatches performed for the Northwestern transplant program over the past 28 months were positive solely due to HLA‐DP donor‐specific antibodies (11%; 16.5% of patients with HLA antibodies—sensitized patients). We further show that 58/207 (12%) HLA‐DR serologically matched donor‐recipient pairs had a positive B cell flow crossmatch due to donor‐specific HLA class II antibodies, and 2/34 (6%) serologic zero‐HLA‐A‐B‐DR mismatch had a positive flow crossmatch due to HLA‐DSA. We therefore provide information regarding the necessity and importance of complete donor HLA typing including both chains of the HLA‐DP antigen (encoded by HLA‐DPA1 and HLA‐DPB1) at the time of organ offer.     

The impact of HLA frequency differences in races on the access to optimally HLA-matched cadaver renal transplants. The Medical Advisory Committee.

We examined the donor/recipient HLA match of 448 consecutive cadaver renal transplants to determine if donor race had an impact on the quality of HLA match that was achieved. Eighty (17.9%) kidneys from black donors and 368 (82.1%) from nonblack donors (87.8% caucasians) were distributed to the blood type compatible and crossmatch negative recipients on the basis of a local variance of the United Network for Organ Sharing (UNOS) point system. There were 278 (62%) nonblack and 170 (38%) black recipients, numbers close to those of nonblacks and blacks on the waiting list (59% and 41%, respectively). Kidneys from nonblack donors represented 86% (240/278) of transplants for nonblack and 75% (128/170) of transplants for black recipients. The best matches, i.e., zero-A,B,DR, zero-A,B, zero-B,DR, and 1-A,B,DR mismatches, for nonblack recipients were solely derived from the nonblack donors, and the few well-matched kidneys from black donors were distributed to black recipients. Black recipients with zero mismatches were few (3, 2%) compared with nonblacks (21, 8%). Kidneys received by black recipients were more likely to be poorly matched (5-6 mismatches) if coming from nonblack donors (57/128, 44%) than black donors (11/42, 26%), P = 0.035. It was also observed from HLA frequency comparisons that well-matched kidneys from nonblack donors were rarely distributed to black patients with HLA phenotypes unique to or more common in blacks who represented a sizeable portion of blacks on the waiting list. We conclude that better donor/recipient HLA matches are achieved when both donors and recipients are of the same race. Thus a larger number of black donors are needed to improve the quality of HLA matching for potential black kidney transplant recipients.     

Virtual Crossmatch in Kidney Transplantation

Background

The Luminex Single-Antigen Beads (LSA) assay allows an accurate detection and characterization of preexisting donor-specific antibodies (DSA) in kidney transplant candidates. But the ability of LSA to detect quite low levels of antibodies makes it hard to correctly predict crossmatch results in donor selection. In this study we retrospectively analyzed the accuracy of our virtual crossmatch (v-XM) protocol, which was used for selection of potential kidney transplant recipients, in predicting the results of actual crossmatch (a-XM) in cadaver-donor renal transplantation. We also investigated correlation between negative a-XM results and strength/specificity of preformed DSA.

Methods

The correlation between negative v-XMs and a-XMs performed in 2007–2012 at the Regional Transplant Center of the Lazio Region, Italy, was analyzed. In carrying out v-XM, the donor HLA molecules against which patients showed LSA-detected DSA with normalized mean fluorescence intensity (MFI) ≥5,000 were considered to be “unacceptable DSA,” and LSA-DSA showing MFI <5,000 were defined as “acceptable DSA.” All cadaver donors had been typed for HLA-A, -B, -DR, and -DQB molecules by sequence-specific primer methods. On the basis of a negative v-XM, we performed 507 a-XMs between serum samples from 256 renal transplant candidates and T/B lymphocytes from 302 cadaver donors with the use of both complement-dependent cytotoxicity (CDC) and flow cytometry (FC) methods.

Results

The v-XM negative results showed good correlation with both CDC and FC a-XMs (97% and 90%, respectively). The sensitivity of v-XM was 100%; this high value was related to the lack of false-negative DSA results. The limited specificity with both techniques (CDC-XM, 74%; FC-XM, 79%) was due to the presence of “acceptable” and/or anti-DQA/DPB DSA in some patient sera used to perform the a-XMs. During the study period, 171 (67%) of the 256 sensitized patients received a kidney transplant: 30% of these had “acceptable DSA” and/or anti-DQA/DPB DSA. No antibody-mediated rejection due to preformed HLA-DSA was observed.

Conclusions

Our v-XM protocol showed high sensitivity in predicting donor-recipient immunologic compatibility. The results of this study also demonstrated the importance of evaluating DSA strength for implementing v-XM results in the selection of kidney transplant recipients. Moreover, the finding of anti-DQA/DPB DSA, especially in serum samples that gave positive results with the use of both CDC and FC a-XMs, highlights the importance of defining all of the donor HLA molecules to perform an accurate v-XM.     

Successful living donor renal transplantation despite ABO incompatibility and a positive crossmatch

Potential live kidney donors have been rejected when the prospective recipients are blood type or crossmatch incompatible. By utilizing plasmapheresis combined with intravenous immune globulin (PP/IVIg) prior to surgery, donor-specific antibodies against blood group or human leukocyte antigens (HLA) have been removed, thereby allowing successful renal transplantation. A 26-yr-old male with a panel reactive antibody level of 100% and repeated positive crossmatches against deceased donor kidney offers, including zero HLA mismatched donors, successfully underwent ABO-incompatible kidney transplantation from his HLA-identical but nevertheless crossmatch-incompatible sister. The initial anti-A blood group isoagglutinin titers were 128, 256, and 1024 at room temperature, 37 degrees C, and 37 degrees C anti-IgG enhanced, respectively. With an individualized PP/IVIg regimen based on donor-specific antibody titer, however, the relevant antibodies were adequately reduced and hyperacute rejection avoided. Subsequent antibody-mediated rejection, likely directed against a minor histocompatibility antigen, was diagnosed on postoperative day 7 and successfully treated. Neither ABO, or crossmatch incompatibility, or both in combination prohibit kidney transplantation.     

Successful Renal Transplantation across Simultaneous ABO Incompatible and Positive Crossmatch Barriers

ABO incompatibility and human leukocyte antigen (HLA) sensitization remain the two largest barriers to optimal utilization of kidneys from live donors. Here we describe the first successful transplantation of patients who were both ABO incompatible and crossmatch positive with their only available donor. A preconditioning regimen of plasmapheresis (PP) and low-dose CMV hyperimmune globulin (CMVIg) was delivered every other day until donor-specific antibody (DSA) titers were reduced to a safe level and isoagglutinin titers were < or =16. Each patient received quadruple sequential immunosuppression, splenectomy and three protocol post-transplant PP/CMVIg treatments. There was no hyperacute rejection. Two of the three patients had a persistent positive cytotoxic crossmatch on the day of transplant and eliminated their DSA subsequently. Antibody-mediated rejection (AMR) in one patient was reversed by reinitiating PP/CMVIg and anti-CD20. The patients are more than 9 months post-transplant with excellent graft function. Preconditioning with PP/CMVIg results in a durable suppression of DSA and permits accommodation of the allograft to a discordant blood type. The ability to cross these two barriers simultaneously is clinically important as sensitized patients have often exhausted their blood type compatible living donors during previous transplants.     

Calculated PRA: Initial Results Show Benefits for Sensitized Patients and a Reduction in Positive Crossmatches

The calculated panel reactive antibody (CPRA), which is based upon unacceptable HLA antigens listed on the waitlist form for renal transplant candidates, replaced PRA as the measure of sensitization among US renal transplant candidates on October 1, 2009. An analysis of the impact of this change 6 months after its implementation shows an 83% reduction in the number of kidney offers declined nationwide because of a positive crossmatch. The increasing acceptance and utilization of unacceptable HLA antigens to avoid offers of predictably crossmatch‐positive donor kidneys has increased the efficiency of kidney allocation, resulting in a significant increase in the percentage of transplants to broadly sensitized (80+% PRA/CPRA) patients from 7.3% during the period 07/01/2001–6/30/2002 to 15.8% of transplants between 10/1/09–3/31/10. The transplant rates per 1000 active patient‐years on the waitlist also increased significantly for broadly sensitized patients after October 1, 2009. These preliminary results suggest that ‘virtual’ positive crossmatch prediction based on contemporary tools for identifying antibodies directed against HLA antigens is effective, increases allocation efficiency and improves access to transplants for sensitized patients awaiting kidney transplantation.     

Kidney Transplantation in Patients with Antibodies against Donor HLA Class II

The immunologic risk associated with donor-specific antibodies (DSA) against Class II human leukocyte antigens (HLA) in kidney transplant (KTx) recipients is unclear. The aim of this study was to determine the outcome of KTx when DSA was detected only against HLA Class II. To isolate the impact of anti-Class II DSA, we retrospectively analyzed 12 KTx recipients who at baseline had a positive B-cell flow cytometric crossmatch (FXM) and a negative T-cell FXM. Using alloantibody specification analysis, 58.3% (7/12) had DSA against donor Class II and 41.7% had no demonstrable DSA. Biopsy-proven AMR occurred in 57% (4/7) in the Class II(+) group and 0% in the Class II(-) group (p > 0.05). Peritubular capillaries stained positive for C4d in 86% (6/7) of the Class II(+) patients and in 40% (2/5) of the Class II(-) patients (p > 0.05). One patient in the Class II(+) group lost their graft at 3 months to accelerated transplant glomerulopathy, while all other grafts were functioning 3-37 months posttransplant despite the persistence of anti-Class II DSA. We conclude that KTx recipients with clearly defined anti-Class II DSA are at risk for humoral rejection suggesting that desensitization and/or close posttransplant monitoring may be needed to prevent AMR.     

Positive crossmatches against mandatorily shared kidneys.

From October 1987 through February 1990 approximately 8.5% (29/341) of all donor kidneys shipped under the UNOS Mandatory Sharing Policy were denied to 27 intended recipients due to a positive final crossmatch [XM(+)]. The intended recipients included 18.5% hispanics and 7.4% blacks compared to 2.4% and 1.6%, respectively, for XM(-) recipients (1-3). Further, more were highly sensitized with 81% having a current PRA greater than 10% and 56% with a peak PRA greater than 80% compared to 65% and 14%, respectively, for XM(-) recipients. More importantly, 19/27 (70%) of the recipient candidates may have had irrelevant positive XMs. The XM(+) patients were classified into five categories defined by: I) autoantibodies; II) transfusions in the 2 weeks prior to the availability of the donor; III) the XM technique; IV) highly sensitized regraft candidates with current and peak PRAs greater than 85% and V) antibody to unreported MHC antigens. Of these, 70% may have been denied a transplant due to IgM autoantibodies or the use of XM techniques lacking extensive evaluation. The authors propose that all XM(+) mandatorily-shared kidneys be examined for IgM autoantibody and that kidneys not be denied to potential recipients due to IgM autoantibody. In addition, to minimize exclusions based on positive B-cell XMs, it is proposed that mandatorily-shared kidneys be shared on the basis of the DR subtypes, insofar as is currently practical.     

Detection of donor-specific anti-HLA class I and II antibodies using antibody monitoring system

The antibody monitoring system (AMS, GTI Inc) is a solid enzyme-linked immunosorbent assay (ELISA) crossmatch test for the detection of immunoglobulin G (IgG) antibody to donor-specific solubilized HLA class I and class II antigens. The objective of this study was to compare the results of the AMS assay with donor-specific anti-HLA IgG antibodies (DS-HLA Abs), as determined by ELISA panel reactive antibody (PRA) and the flow cytometric crossmatch test (FCXM). A total of 107 sera were screened for the presence of HLA Abs by ELISA PRA (LAT-M, One-Lambda Inc), the DS-HLA Abs were determined in 34 serum samples (31.8%) by an ELISA panel (LAT class I and class II, One-Lambda Inc) and FCXM. The FCXM and AMS assays were performed with matched lymphocytes from 56 donors. There was a significant degree of concordance (89.7%) between the two tests (P < .001). The sensitivity, specificity, positive predictive value, and negative predictive value of AMS assay to detect DS-HLA Abs was 88.2%, 94.5%, 88.2%, and 94.5%, respectively. The AMS is a simple, objective test, which has several advantages over the cell-based crossmatch test, such as elimination of non-HLA antibody reactivity, elimination of non-donor-specific antibody reactivity, no need for viable cells, and preparation of the donor's HLA antigens in advance. In summary, this study suggested that AMS may be useful as a supportive crossmatch test or as a monitoring test after transplantation to detect class I or class II DS-HLA Abs.     

Assignment of C1q-binding HLA antibodies as unacceptable HLA antigens avoids positive CDC-crossmatches prior to transplantation of deceased donor organs

Soon, a virtual crossmatch shall replace the complement-dependent cytotoxicity (CDC) allocation crossmatch in the Eurotransplant region. To prevent positive CDC-crossmatches in the recipient centre, careful definition of unacceptable antigens is necessary. For highly sensitized patients, this is difficult by CDC alone. Assignment of all antibodies detected by sensitive assays, however, could prevent organ allocation. To assess the usefulness of the Luminex C1q-assay to prevent positive CDC-crossmatches, all CDC-crossmatches performed prior to deceased kidney transplantation in a 16-month-period were reviewed. Sera causing positive crossmatches were investigated by the C1q-assay. 31 out of 1432 crossmatches (2.2%) were positive. Sera involved in 26 positive crossmatches were available. C1q-binding donor-specific antibodies were detected in 19 sera (73.1%). The other sera were from recipients without any HLA antibodies detectable by CDC or common solid phase assays. Three patients had known Non-HLA antibodies causing positive CDC-results. Four crossmatches were only weak positive. Therefore, avoidance of donors with HLA antigens against whom C1q-binding antibodies were detected would have prevented all positive crossmatches due to HLA antibodies. Provided that all HLA specificities against which antibodies are detected by the Luminex C1q-assay are considered as unacceptable antigens, CDC-crossmatches prior to transplantation might safely be omitted in many patients. They should be maintained in highly immunized patients, however, for whom assignment of all C1q-positive antibodies as unacceptable antigens could lead to a significant delay or even prevention of transplantation.     

Antibody-mediated rejection of a unilateral donor lung in bilateral living-donor lobar lung transplantation: report of a case

We report a case of antibody-mediated rejection (AMR) of a unilateral donor lung in the presence of newly formed donor-specific antibodies, 10 months after living-donor lobar lung transplantation (LDLLT). Of note is that the AMR occurred in the unilateral lung. Furthermore, the lung graft was from her husband and HLA analysis on the recipient's daughter revealed the same donor-specific HLA antigens, which strongly suggested pre-sensitization before lung transplantation. Fortunately, we could perform direct crossmatch even 1 year after lung transplantation because of the living donors.     

Transplanting the Highly Sensitized Patient: The Emory Algorithm

Renal transplant patients sensitized to HLA antigens comprise nearly one-third of the UNOS wait-list and receive 14% of deceased donor (DD) transplants, a rate half that of unsensitized patients. Between 1999 and 2003, we performed 492 adult renal transplants from DD; 120 patients (approximately 25%) had a panel reactive antibody (PRA) of >30%, with nearly half (n = 58) having a PRA of >80%. Our approach is based upon high-resolution solid-phase HLA antibody analysis to identify class I/II antibodies and a 'virtual crossmatch' to predict compatible donor/recipient combinations. Recipients are excluded from the United Network for Organ Sharing match run if donors possess unacceptable antigens. Thus, when sensitized patients appear on the match run, they have a high probability of a negative final crossmatch. Here, we describe our 5-year experience with this approach. Five-year graft survival ranged from 66% to 70% among unsensitized (n = 272), moderately sensitized (PRA < 30%, n = 100) and highly sensitized (>30% PRA; n = 120) patients, equal to the average national graft survival (65.7%). The application of this approach (the Emory Algorithm) provides a logical and systematic approach to improve the access of sensitized patients to DD organs and promote more equitable allocation to a highly disadvantaged group of patients awaiting renal transplantation.     

HLA Points Assigned in Cadaveric Kidney Allocation Should Be Revisited: An Analysis of HLA Class II Molecularly Typed Patients and Donors

The points now assigned for the quality of HLA match have received significant scrutiny to be modified in an effort to help reduce disparity in access to kidneys of minority groups, and since differences in graft survival between groups of patients in each of the HLA matched groups is less now than in the past. We analyzed long-term (5-year) graft survival in 746 DR DNA typed recipients of cadaveric kidneys transplanted from 1994-2001 whose donors were also DR DNA typed, with allocation based on those DNA-based typings. Five-year graft survival was not significantly different for recipient groups irrespective of if they had zero (84%), one (92%), two (89%), or three to four B, DR mismatches (79%) (log-rank = 0.15; died with a functioning graft [DWFG] censored). Mismatching of three and four DR and DQ antigens in black but not white patients was associated with significantly worse survival (Relative Risk = 2.9) (p = 0.002). The incidence of minority transplants in the well-matched group (zero and one B, DR mismatch), 12.8% (20/156) was over half that of the less well-matched group, 27.1% (160/590) (p < 0.001). Our data indicate that the current HLA-B, DR-based point system used to allocate kidneys warrants re-evaluation. Our data, taken in the context of the UNOS data, which has recently been re-evaluated, suggest that the only HLA-DR remain as a component of the national kidney allocation algorithm so as to increase access of kidneys to minorities and minimize graft loss.     

Harnessing Scientific and Technological Advances to Improve Equity in Kidney Allocation Policies

We reported that current assignment of HLA‐DQ is a barrier to organ allocation. Here we simulated the impact of incorporating HLA‐DQ antigens and antibodies as A/B and αβ allelic variants, respectively, on calculated panel reactive antibody (cPRA) and probability of finding potential compatible donors (PCD). A cohort of 1224 donors and 2075 sensitized candidates was analyzed using HLA‐DQαβ allelic (study) versus serologic (current practice) nomenclature. A significant (p < 10^?4) decrease in cPRA was observed with higher impact for male versus female, and first transplant versus retransplant (p < 10^?4), affecting mostly patients with moderate cPRA (30–80%). Consequently, the number of patients qualifying for 100% cPRA points according to the United Network for Organ Sharing–Kidney Allocation System decreased by 37%. More critically, by using allelic versus serologic nomenclature for HLA‐DQ, the number of PCDs for all patients was increased, with male and first‐transplant patients showing a higher expansion compared with female and retransplants. Patients of blood group O showed the highest benefit. The goal of reporting unacceptable antigens is to improve accuracy of virtual crossmatching and increase the likelihood of finding immunologically compatible donors. Our simulation provides strong support for the need to re‐evaluate the use of allele typing and how HLA‐DQ antigens and antibodies are incorporated into allocation policies to ensure equity.     

Sensitized patients require sharing of highly matched kidneys

BACKGROUND: Improved HLA matching can allow for renal transplantation in sensitized patients. United Network for Organ Sharing (UNOS) is currently considering removing the points awarded for HLA matching. METHOD: Twenty-six transplant centers shared kidneys, according to the algorithm: A, UNOS mandatory 0-mismatch (MM) share; B, UNOS mandatory 0-mm payback; C, 0 - B,Dr-MM; PRA> or = 40%; ROP tray negative; D, 0-B,Dr-MM; panel reactive antibodies (PRA) <40%; E, 0-B,Dr payback; F, local use. RESULTS: A total of 354 patients received transplants through the program and were compared with 6492 control patients. There was a significantly greater primary nonfunction rate in sensitized patients in spite of similar length cold ischemia time. Blacks were not significantly disadvantaged by the HLA matching requirements of the program. White recipients were favored by the matching program to the detriment of race group "other." Women were more frequently found in the sensitized groups but were not favored by sharing. Retransplant patients and patients with current PRA > or = 40% were favored by the sharing program. Sharing for HLA match does not improve graft survival at 1, 2, 3 years. CONCLUSIONS: (1). Elimination of suboptimal HLA matching by UNOS will probably not adversely affect 1-, 2-, and 3-year graft survival; (2). Removing the consideration for HLA matching will result in fewer transplant opportunities for highly sensitized patients such as retransplants and currently sensitized patients.     

Hepatitis C virus infection and lung transplantation: a survey of practices.

BACKGROUND: Approximately 4 million persons in the United States are chronically infected with hepatitis C and morbidity due to this disease is increasingly observed in transplant recipients. While knowledge of hepatitis C in liver and kidney transplantation is advancing, little information is available concerning hepatitis C and lung transplantation. We surveyed lung transplant programs about policies regarding testing for hepatitis C, transplantation of hepatitis C-infected candidates, and the use of organs from seropositive donors. METHODS: A written questionnaire was sent to all United Network of Organ Sharing (UNOS) approved lung transplant programs. RESULTS: Fifty-nine of 89 (66%) surveys were returned, including 49 from active programs, capturing 81% of lung transplants performed within UNOS prior to January 1998. All programs screen candidates for hepatitis C. The estimated median seropositivity rate among candidates was 1.9%. Thirty-three of 46 (72%) programs consider seropositive patients for transplantation and most use virologic and/or histologic data to determine candidacy. All donors are screened for hepatitis C. Twenty-six of 47 (55%) programs accept lungs from seropositive donors and many restrict the use of organs from seropositive donors to infected recipients. Few programs routinely test recipients for hepatitis C, and policies for monitoring those with known infection are variable. CONCLUSIONS: Lung transplant candidates and donors are tested routinely for hepatitis C. The majority of programs are willing to accept infected candidates and seropositive donors. Post-transplant follow-up of hepatitis C is variable and prospective studies are needed to evaluate the impact of hepatitis C on lung transplant recipients.     

Prediction of negative crossmatch: an aid for cost-effective kidney sharing

Prospective kidney transplant recipients, who have broadly reactive cytotoxic antibodies, are currently at a considerable disadvantage in competing for shared kidneys since they tend not to be considered as candidates because of the likelihood of kidney wastage subsequent to positive crossmatch tests. Alternative to extensive shipping, storage and crossmatch testing by the harvesting center, is the prediction of crossmatch outcome on the basis of donor HLA type and recipient sera characteristics. A prediction method was developed that yields approximately 85% correct predictions. The method was validated by predicting crossmatch outcome of 67 consecutive cadaveric donors tested against 87 recipients and is suggested as useful for guiding kidney sharing programs.     

Clinical importance of anti-human leukocyte antigen-specific antibody concentration in performing calculated panel reactive antibody and virtual crossmatches

BACKGROUND: Highly sensitized patients develop multi-human leukocyte antigen (HLA) specific antibodies. This study measures concentrations of anti-HLA antibodies in multispecific sera by converting fluorescence intensity into molecules of equivalent soluble fluorochrome (MESF) units. This was used to determine MESF units required for a positive T and B flow crossmatches (FLXM). METHODS: MESF values of negative controls and sera from patients devoid of HLA antibodies were measured by FLXM and flow panel reactive antibody (PRA) screening beads. Fluorescence intensity values of anti-HLA specific antibodies determined by FlowPRA single antigen beads of highly sensitized patients were converted into MESF units. In addition, endpoint titers, MESF units, and % PRA of 26 sera were established. RESULTS: MESF analysis accurately predicted the outcomes of 100% of T and B FLXM of sera with strong (MESF units>18,000) donor-specific antibody (DSA). The predictive values of T and B FLXM declined to 95% and 88% with weak DSA (6,000 MESF<10,000). Endpoint titers of sera from highly sensitized patients ranged from 1:512 to 1:8 with corresponding MESF values of 452,596 to 20,000 units. However, there was no statistical difference in PRA values among these sera (95%-100%). We successfully transplanted five patients who had weak donor-specific HLA antibodies (MESF units>2,000). The graft survival at 1 year was 100% and there was no evidence of DSA posttransplant. CONCLUSION: MESF analysis is both a time and cost efficient way of measuring antibody strength. The strength of the antibody present in the sera of transplant candidates is critical for crossmatch prediction.     

Comparative analysis of two methods to detect donor-specific anti-HLA antibodies after kidney transplant

Preformed anti-human leukocyte antigen (HLA) antibodies may be present in the blood of kidney transplant candidates. The production of these antibodies may occur in the post-transplant period, with the possible development of donor-specific antibodies (DSA). Luminex-based tests, such as the single antigen (SA) assay and the Luminex crossmatch (Xm-DSA) assay are the most commonly used tools to detect anti-HLA antibodies, due to their high sensitivity and specificity. This cross-sectional study aimed to compare the findings of two methods for the detection of DSAs after kidney transplant: SA and Xm-DSA. A total of 122 patients who underwent deceased donor kidney transplant at Hospital de Clínicas de Porto Alegre were included. The SA assay detected anti-class I HLA DSAs in 17 patients (13.9%) and anti-class II HLA DSAs in 22 patients (19.6%), whereas the Xm-DSA detected DSAs in 18 patients (14.8%) both against class I and class II antigens. There was agreement between the two methods for class I (kappa = 0.66, p = 0.001) and class II (kappa = 0.54, p = 0.025) antigens. The incidence of DSAs as obtained by the SA assay was 15.57%, and the most prevalent DSAs were those against HLA-DR antigens. Patient survival at 3 years was 92%. The two techniques assessed in this study provide important information on the presence of DSAs and may help in the post-transplant patient monitoring and in immunosuppressive strategy.