Negative Crossmatch Research Articles

83 Detection of Class I Anti-HLA Antibodies by Luminex Pre-Transplant Predicts Poor Outcomes Following Lung Transplantation

Purpose Solid phase assays detect anti-HLA antibodies with high accuracy and sensitivity, however debate continues on how these results should be interpreted in the setting of lung transplantation. Methods and Materials We performed a retrospective analysis of pre-transplant anti-HLA antibody levels detected using a solid-phase HLA microbead assay (Luminex) in 80 patients undergoing lung transplantation at a single centre between 1/1/09 and 1/5/10. All patients underwent prospective T- and B-cell crossmatches (complement-dependent cytotoxicity assays) prior to transplantation. Outcome variables analyzed included acute cellular and antibody-mediated rejection, BOS and survival. Results Pre-transplant class I and class II anti-HLA antibodies were present in 31/80 (38%) and 13/80 (10%) patients, respectively, but did not predict a positive T- or B-cell crossmatch which was weekly positive in 1/80 and 14/80 patients, respectively. HLA class I and II donor-specific antibodies (DSA) were present pre-transplant in 13 and 7 patients, respectively. The presence pre-transplant of class I DSA, irrespective of a negative prospective T- and B-cell crossmatch predicted for a poor outcome (Odds ratio for BOS/death 4.6, p = 0.03). Pre-transplant DSA was not associated with the subsequent development of either acute cellular or antibody-mediated rejection. Only two patients developed clinically significant antibody-mediated rejection. Both developed DSA following transplant having not been present pre-transplant. Conclusions Identifying DSA pre-transplant predicts poor outcomes post-transplant and provides prognostic information beyond that which has been historically provided by a negative prospective crossmatch. Future studies need to focus on defining the level of pre-transplant DSA as measured using solid phase assays that predict for adverse outcomes following lung transplantation.

Kidney transplantation in highly sensitized patients: are there options to overcome a positive crossmatch?

Presensitization against a broad array of human leukocyte antigens (HLA) is associated with prolonged waiting times and inferior graft survival in kidney transplantation. Since the late 1960s, a positive lymphocytotoxic crossmatch has been considered a contraindication for kidney transplantation and solutions, such as enrollment of eligible patients in the Acceptable Mismatch Program of Eurotransplant and kidney paired donation in the case of living donor kidney transplantation, have been proposed to avoid this barrier. Alternatively, a positive crossmatch might not be considered as a contraindication for kidney transplantation and one can try to overcome this hurdle by desensitization. In principle, there are three different ways to overcome the crossmatch barrier by desensitization. The highly sensitized patient awaiting a cadaveric kidney transplant may be desensitized either immediately pretransplant when an organ is offered or in advance, during the time on the waiting list, to increase his chance of having a negative crossmatch at the time of transplantation. In the case of living donor kidney transplantation, the patient can be desensitized for days to weeks until the positive crossmatch with his intended living kidney donor becomes negative. "Heidelberg algorithm" is a combination of different measures, such as pretransplant risk estimation, good HLA match, inclusion of patients in the Eurotransplant Acceptable Mismatch program, and desensitization, which leads to timely transplantation and excellent survival rates in highly sensitized patients at a low rate of toxicity. We believe that all available options should be utilized in an integrated manner for the transplantation of kidney transplant recipients who are at a high risk of antibody-mediated rejection.

Interpretation of Positive Flow Cytometric Crossmatch in the Era of the Single-Antigen Bead Assay

Prognosis of renal transplants with positive flow cytometric crossmatch (FCXM) remains controversial. We analyzed the outcome of these kidney transplant recipients by human leukocyte antigen (HLA) donor-specific antibodies (HLA-DSA) using single-antigen bead (SAB) assays in major histocompatibility complex classes I and II. We compared them with controls with a negative FCXM. Forty-five patients consecutively transplanted with a positive FCXM had significantly more acute rejection episodes than the control patients (33.3% vs. 8.9%, P=0.002). Risk of acute rejection was increased with day 0 (D0) positive T-cell FCXM (odds ratio [OR]=9.04, P=0.002), D0 positive B-cell FCXM (OR=7.43, P=0.02), and D0 HLA-DSA identified by SAB assay (OR=6.5, P=0.03). The 21 patients with D0 positive FCXM and D0 HLA-DSA had more acute rejection (62%, P=0.0001) and a lower estimated glomerular filtration rate 1-year posttransplantation (P=0.0001), when compared with controls. Mainly anti-Cw and anti-DP HLA-DSA were found in patients displaying acute rejection. The remaining FCXM-positive patients displayed short-term outcomes similar to controls. The presence of HLA-DSA detected only by the SAB assay in the context of a negative FCXM crossmatch was not associated with increased risk of acute rejection. Identification of HLA-DSA in D0 sera by the two sensitive techniques FCXM and SAB assay indicates which patients are at highest risk of subsequent acute allograft rejection and chronic allograft dysfunction.

Donor-specific antibody against denatured HLA-A1: Clinically nonsignificant?

Pre-transplant screening of a woman with end-stage renal disease (ESRD) showed no anti–human leukocyte antigen (HLA) alloantibodies by anti-human globulin–complement-dependent cytotoxicity (AHG-CDC; class I) or enzyme-linked immunosorbent assay (class II). Following a negative AHG-CDC crossmatch, an HLA*01:01+ deceased donor (DD) kidney was transplanted in September 2005. Subsequent screening of pre-transplant serum by LABScreen Single Antigen (SA) array showed strong reactivity versus A*01:01. Despite that reactivity, at 5 years post-transplant, the patient has a serum creatinine of 1.6 mg/dl and has never experienced humoral or cellular rejection. Retrospective flow-cytometric crossmatch of pre- and post-transplant sera versus DD cells was negative. Rescreening of multiple pre- and post-transplant sera revealed anti-A1 reactivity persisting from the first through the last samples tested. The patient's anti-A1 was almost two fold more reactive with denatured A*01:01 FlowPRA SA beads after denaturation with acid treatment (pH 2.7) than with untreated beads. Parallel results were observed with pH 2.7 treated versus untreated A1+ T cells in FXM. These data highlight the difficulty in interpreting screening results obtained using bead arrays, because of antibodies that appear to recognize denatured but not native class I HLA antigens. We suggest that such bead-positive, flow cytometric crossmatch negative antibodies are not associated with humoral rejection, may not necessarily be detrimental to a graft, and deserve further evaluation before becoming a barrier to transplantation.

Outcome of Patients with Preformed Donor-Specific Antibodies Following Alemtuzumab Induction and Tacrolimus Monotherapy

It has been shown that low-level preformed donor-specific antibodies (DSAbs) detected by luminex beads in the setting of a negative CDC and flow cytometry crossmatch (CDC/FCXM) are associated with inferior allograft outcomes. The relevance of preformed DSAbs in patients receiving alemtuzumab induction and tacrolimus monotherapy has not been studied. Four hundred and eighty renal transplant recipients with a negative CDC/FCXM had their pretransplant sera retrospectively screened for DSAbs. 45/480 (9.4%) of patients were found to have preformed DSAbs. Females and patients receiving regrafts were more likely to have a DSAb (p = 0.008 and p < 0.0001, respectively). Patients with DSAbs had inferior allograft survival (p = 0.047), increased incidence of antibody-mediated rejection (p < 0.0001) and inferior allograft function at 6 months posttransplant (p = 0.017). Patients with HLA class I DSAb (alone or in combination with a Class II DSAb) with high mean fluorescence intensities (MFIs) were at highest risk. We conclude that patients with preformed DSAb are at high risk of adverse outcomes when receiving a minimal immunosuppressive regime incorporating alemtuzumab induction. Patients found to have a preformed DSAb despite a negative crossmatch might benefit from augmented immunosuppression.

The impact of donor-specific antibodies on graft outcome in pediatric renal transplantation from deceased donors

Despite prospective crossmatching and modern immunosuppression, early acute rejection is still present in cadaveric renal transplantation. The purpose of this study was to evaluate the incidence of preformed anti-donor antibodies, detected by 2 solid-phase techniques, and to analyze their impact on early renal allograft outcome. Flow crossmatch detecting the presence of anti-donor IgG and IgM antibodies was performed in pre-transplant sera of 279 patients with negative cytotoxic crossmatch. Screening for IgG antibodies detected by bead-based multiplex technique was performed in sera of 69 patients from the FCXM group. The incidence of early biopsy-proven rejection and graft failure within 3 months after transplantation was analyzed. Anti-donor IgG antibodies were detected in 33 patients (11.8%) by flow crossmatch and in 10 patients by multiplex (14.5%). IgM antibodies were detected in 23 patients (8.2%). All multiplex-positive sera were also positive for IgG by flow crossmatch, but in 18 cases no antibodies were found by multiplex technique. Biopsy-proven acute rejection within 3 months after transplantation was observed in 16 patients, and 5 allografts were lost due to immunological reasons. Presence of IgG antibodies was found to have no effect on early outcome, while the presence of IgM antibodies was associated with significantly higher rejection rate and immune-related graft failure. Anti-donor IgG antibodies detected by bead-based and cell-based technique have no impact on biopsy-proven rejection rate or graft failure. Anti-donor IgM detected by flow crossmatch have significant impact on early transplantation outcome.

Type and screen policy in the blood bank: Is AHG cross-match still required? A study at a multispecialty corporate hospital in India

Background:Antibodies against only about 25–28 blood group antigens are known to cause hemolytic reactions (HTRs), and red cell antibody screening should detect such clinically significant antibodies. An extension of the antibody screening test is the ‘type and screen’ done to detect clinically significant antibodies, omiting the anti-human globulin (AHG) cross-match.Aim:The aim of this study was to find out if the type and screen procedure is a safe method for pre-transfusion testing when compared to the AHG cross-match currently in use in India.Materials and Methods:We evaluated data from 45373 patients for whom a total of 61668 units of packed red blood cells (PRBC) were cross-matched in the AHG phase using DiaMed® ID cards. An antibody screen was carried out in all the patients using the DiaMed® ID-DiaCell I+II+III. The AHG cross-match was also carried out for all recipients, irrespective of the result of the antibody screen. The results were compared to see if there were any cases where the antibody screening was negative but the AHG cross-match showed incompatibility.Results:Not a single case was found where the antibody screen was negative and AHG cross-match showed incompatibility. In 68 cases the antibody screening was positive. Out of the 68 cases, AHG cross-match was incompatible with at least one unit of PRBC in 41 cases.Conclusion:The screening cell panel adequately detected the clinically significant antibodies in the Indian population in our study. The type and screen policy can be safe, efficient, cost-effective, and beneficial to the transfusion service in India.

Pretransplant Predictors of Survival After Intestinal Transplantation: Analysis of a Single-Center Experience of More Than 100 Transplants

Outcomes after intestinal transplantation (ITx) have steadily improved. There are few studies that assess factors associated with these enhanced results. The purpose of this study was to examine peri-ITx variables and survival. A review of a prospectively maintained database was undertaken and included all patients undergoing ITx from 1991 to 2010. The study endpoints were patient and graft survival. Data collection included 44 variables. Survival was computed using Kaplan-Meier methods. Univariate analysis was conducted (log-rank test) with significance set at P less than or equal to 0.20. Multivariate analysis of significant variables was conducted using model reduction by backward elimination variable selection method with significance set at P less than 0.05. Eighty-eight patients received 106 ITx. The majority of recipients were male, Latino, and children. The leading causes of intestinal and liver failure were gastroschisis and parenteral nutrition. Grafts transplanted were isolated intestine (24%), liver-intestine (62%), and multivisceral (14%). Overall 1- and 5-year patient and graft survival were 80% and 65%, and 74% and 64%, respectively. Significant univariate survival predictors were weight less than 20 kg, children, liver-inclusive allograft, panel reactive antibody less than 20%, absence of donor-specific antibody, negative crossmatch, warm ischemia time less than 60 min, absence of recipient splenectomy, interleukin-2 receptor antagonist induction, and era. Significant multivariate survival predictors were absence of donor-specific antibody, absence of recipient splenectomy, and liver-inclusive graft type. This large, single-center ITx experience confirms a marked improvement in outcome over time. Several important factors were associated with survival, and these factors can potentially be adjusted before ITx. These findings should refocus future efforts on strategies to improve treatment and prevent graft loss.

The long-term outcome of treated sensitized patients who undergo heart transplantation

Sensitized patients prior to heart transplantation are reportedly at risk for hyperacute rejection and for poor outcome after heart transplantation. It is not known whether the reduction of circulating antibodies pre-transplant alters post-transplant outcome. Between July 1993 and July 2003, we reviewed 523 heart transplant patients of which 95 had pre-transplant panel reactive antibody (PRAs) >10%; 21/95 were treated pre-transplant for circulating antibodies. These 21 patients had PRAs > 10% (majority 50-100%) and were treated with combination therapy including plasmapheresis, intravenous gamma globulin and rituximab to reduce antibody counts. The 74 untreated patients with PRAs > 10% (untreated sensitized group) and those patients with PRAs < 10% (control group) were used for comparison. Routine post-transplant immunosuppression included triple-drug therapy. After desensitization therapy, circulating antibody levels pre-transplant decreased from a mean of 70.5 to 30.2%, which resulted in a negative prospective donor-specific crossmatch and successful heart transplantation. Compared to the untreated sensitized group and the control group, the treated sensitized group had similar five-yr survival (81.1% and 75.7% vs. 71.4%, respectively, p = 0.523) and freedom from cardiac allograft vasculopathy (74.3% and 72.7% vs. 76.2%, respectively, p = 0.850). Treatment of sensitized patients pre-transplant appears to result in acceptable long-term outcome after heart transplantation.

Long-Term Outcomes Using Deceased Donor Kidneys From Cobra Bite Brain Dead Victims

Long-Term Outcomes Using Deceased Donor Kidneys From Cobra Bite Brain Dead Victims

4-OR: Positive Virtual Crossmatch (VXM), Negative Flow Crossmatch (FXM): A Case of Antibody (Abs) to Denatured Antigen (dAg)

4-OR: Positive Virtual Crossmatch (VXM), Negative Flow Crossmatch (FXM): A Case of Antibody (Abs) to Denatured Antigen (dAg)

Cross Matching of Blood in Carcharhiniform, Lamniform, and Orectolobiform Sharks

The transfusion of whole blood in elasmobranchs could provide cardiovascular support following hemorrhage. Since donor and recipient compatibility is not known, a technique was established to allow cross matching of red blood cells and serum in sharks. Cross matching was carried out among 19 individuals from seven species: the nurse shark (Ginglymostoma cirratum), sandbar shark (Carcharhinus plumbeus), sandtiger shark (Carcharias taurus), white-spotted bamboo shark (Chiloscyllium plagiosum), brown-banded bamboo shark (Chiloscyllium punctatum), zebra shark (Stegostoma fasciatum), and spotted wobbegong (Orectolobus maculatus). Negative cross-matches showed no agglutination or hemolysis, suggesting that donor and recipient would be compatible. Cross-matches between conspecifics were all negative (sandbar, sandtiger, nurse, and white-spotted bamboo sharks). All cross-matches between sandbar and sandtiger sharks were also negative. Positive crossmatches consisted of agglutination or hemolysis of red blood cells, suggesting that the donor and recipient would be incompatible. Strong positive reactions occurred, for example, with red blood cells from sandtiger and sandbar sharks and serum from nurse sharks. Cross matching should be carried out in elasmobranchs prior to any blood transfusion.

High negative predictive value of an amplified flow cytometry crossmatch before living donor kidney transplantation

Living kidney donation provides the advantage of assessing immunologic risk in detail before transplantation. It was our aim to analyze how results of an amplified flow cytometry crossmatch (FCXM) predict antibody-mediated rejection. T-cell–specific antibodies were analyzed in 92 donor/recipient pairs (164 datasets, average of 1.8 datasets per pair) with negative lymphocytotoxic crossmatch. FCXM results were expressed as delta values of the median fluorescence intensity (MFI), i.e., donor-specific MFI minus negative control. Based on receiver operating curve analysis, positive FCXM results were defined as delta MFI > 22. Delta MFI values in recipients with vs. without antibody-mediated rejection were significantly higher ( n = 6 vs n = 86, p < 0.005). Recipients were grouped into those with reproducibly negative, varying, and reproducibly positive results ( n = 69, n = 12, and n = 11, respectively). Only one of 69 patients with reproducibly negative results displayed antibody-mediated rejection, yielding a negative predictive value of 99%. Furthermore Fisher's exact test showed that the relative risk of a single positive FCXM result for antibody-mediated rejection is 10.1. Thus a negative T-cell FCXM before kidney transplantation is an excellent predictor of the absence of antibody-mediated rejection.

Baseline Donor‐Specific Antibody Levels and Outcomes in Positive Crossmatch Kidney Transplantation

Renal transplant candidates with donor-specific alloantibody (DSA) have increased risk of antibody-mediated allograft injury. The goal of this study was to correlate the risk of antibody-mediated rejection (AMR), transplant glomerulopathy (TG) and graft survival with the baseline DSA level (prior to initiation of pretransplant conditioning). These analyses include 119 positive crossmatch (+XM) compared to 70 negative crossmatch (-XM) transplants performed between April 2000 and July 2007. Using a combination of cell-based crossmatch tests, DSA level was stratified into very high +XM, high +XM, low +XM and -XM groups. In +XM transplants, increasing DSA level was associated with increased risk for AMR (HR = 1.76 [1.51, 2.07], p = 0.0001) but not TG (p = 0.18). We found an increased risk for both early and late allograft loss associated with very high DSA (HR = 7.71 [2.95, 20.1], p = 0.0001). Although lower DSA recipients commonly developed AMR and TG, allograft survival was similar to that of -XM patients (p = 0.31). We conclude that the baseline DSA level correlates with risk of early and late alloantibody-mediated allograft injury. With current protocols, very high baseline DSA patients have high rates of AMR and poor long-term allograft survival highlighting the need for improved therapy for these candidates.

Virtual crossmatch by identification of donor-specific anti-human leukocyte antigen antibodies by solid-phase immunoassay: A 30-month analysis in living donor kidney transplantation

Selection of donors for kidney transplantation depends on accurate prediction of risk factors for immunologic rejection. Historically, cytotoxicity crossmatch (CXM) examining lysis of donor cells by preformed anti-human leukocyte antigen (HLA) antibodies (Abs) has been considered the best predictor of immunologic rejection. However, there is much interest in defining anti-HLA Ab specificity in recipient sera by immunoassay to predict crossmatch results and aid in donor selection. Current immunoassays for anti-HLA Abs are highly sensitive, though correlation between Abs detected by immunoassay and their functional relevance in CXM and subsequent transplantation is not well defined. In this study, we retrospectively examined the predictive value of detection of donor-specific anti-HLA Abs (DSA) by Luminex Single Antigen assay from 149 consecutive living donor kidney transplant recipients. We demonstrate that detection of DSA by immunoassay accurately predicted negative crossmatch and graft survival. However, this approach had limited sensitivity for predicting positive crossmatch, attributable to either limited typing of donor HLA-DQ and -DP alleles or due to non-HLA Abs. False-positive prediction of CXM correlated with detection of “weak” Abs with low mean fluorescence intensity (MFI < 2000). Furthermore, we found that a ratio of the MFI of the DSA bead to the MFI of the positive control bead was a better method for identifying weak DSA that did not result in CXM-positive reactions. Interestingly, patients with weak DSA and negative CXM had equivalent graft survival over an 18 month follow-up period, suggesting that weak DSA may not preclude transplantation.

Safety and early outcomes using a corticosteroid-avoidance immunosuppression protocol in pediatric heart transplant recipients

Long-term oral corticosteroids have been a mainstay of maintenance immunosuppression in pediatric heart transplantation. In this study, we report early clinical outcomes in a cohort of pediatric heart transplant recipients managed using a steroid-avoidance protocol. Of the 70 patients who underwent heart transplantation during the study period, 55 eligible recipients, including 49 non-sensitized and 6 sensitized (all 55 with negative crossmatch) patients, entered a steroid-avoidance immunosuppression protocol consisting of thymoglobin induction followed by a 2-drug, tacrolimus-based, corticosteroid-free regimen. The primary outcome variable was freedom from moderate rejection (International Society for Heart and Lung Transplantation [ISHLT] Grade 2R/3A or antibody-mediated rejection). The median age at transplant was 7.1 years (range 2 weeks to 22 years) and median follow-up was 19 months (range 2 to 46 months). Fifty patients survived to discharge after transplantation. Of these patients, 2 (4%) were discharged on steroids and 8 (16%) started on maintenance steroids at follow-up. Rejection was diagnosed in 8 patients (Grade 2R cellular rejection in 3 and antibody-mediated rejection in 5). Freedom from rejection was 92% at 6 months (95% confidence interval [CI] 80% to 97%) and 87% at 1 year (CI 73% to 94%). Post-transplant survival was 91% at 6 months (CI 79% to 96%) and 88% at 12 and 24 months (CI 75% to 95%). There was 1 death due to rejection (antibody-mediated) 8 months after transplantation. An immunosuppression protocol consisting of induction followed by corticosteroid avoidance appears to achieve acceptable rejection rates during the first year post-transplant in pediatric heart transplant recipients.

Living unrelated donor kidney transplantation: A fourteen-year experience

In countries without a national organization for retrieval and distribution of organs of the deceased donors, problem of organ shortage is still not resolved. In order to increase the number of kidney transplantations we started with the program of living unrelated - spousal donors. The aim of this study was to compare treatment outcome and renal graft function in patients receiving the graft from spousal and those receiving ghe graft from living related donors. We retrospectively identified 14 patients who received renal allograft from spousal donors between 1996 and 2009 (group I). The control group consisted of 14 patients who got graft from related donor retrieved from the database and matched than with respect to sex, age, kidney disease, immunological and viral pretransplant status, the initial method of the end stage renal disease treatment and ABO compatibility. In the follow-up period of 41 +/- 38 months we recorded immunosuppressive therapy, surgical complications, episodes of acute rejection, CMV infection and graft function, assessed by serum creatinine levels at the beginning and in the end of the follow-up period. All patients had pretransplant negative cross-match. In ABO incompatible patients pretransplant isoagglutinine titer was zero. The patients with a spousal donor had worse HLA matching. There were no significant differences between the groups in surgical, infective, immunological complications and graft function. Two patients from the group I returned to hemodialysis after 82 and 22 months due to serious comorbidities. In spite of the worse HLA matching, graft survival and function of renal grafts from spousal donors were as good as those retrieved from related donors.

Sharing kidneys across donor-service area boundaries with sensitized candidates can be influenced by HLA C

The United Network for Organ Sharing (UNOS) implemented the virtual crossmatch system in UNet as a way to improve the likelihood of a negative crossmatch when kidneys are shared with HLA-sensitized candidates across donor service area (DSA) boundaries. The role of HLA C in that process is not universally appreciated. We recently experienced an unexpected positive flow T and B cell crossmatch for an imported, HLA zero-mismatched kidney because of donor-specific HLA C antibodies and transplanted it into the backup candidate. HLA C locus antigens were not typed by the OPO's laboratory that sent the kidney so the UNet virtual crossmatch could not "strike" our candidate from the UNOS match run. HLA C locus typing data of donors for kidneys our DSA imported from other DSAs revealed that C typing was not performed in 23% (14/60) and was discrepant with our molecular type for 10% (6/60) and was concordant in 67% (40/60) of cases. The rate of positive donor-specific crossmatches was higher (83%) for HLA C discrepantly typed donors than for concordantly typed donors (44%). Sensitization for HLA C (42%) is less frequent than for A (80%) or B (83%) locus antigens but the immunogenicity of C locus antigens in patients who make C locus antibodies is equivalent in black and white patients. Finally, the transplant rate of imported kidneys into class I-sensitized candidates was 24%, and C locus-sensitized candidates comprised 55% of those transplanted.

Utility of the virtual crossmatch in solid organ transplantation

Solid-phase assays covered with single HLA molecules - such as single-antigen flow-beads (SAFBs) - allow determining the presence of donor-specific HLA antibodies (HLA-DSAs) 'virtually' by comparison of the HLA-antibody specificities of the recipient with the HLA typing of the donor. In this review, prospects and current limitation of the virtual crossmatch are discussed. Several prospective and retrospective studies indicate that a negative virtual crossmatch is associated with a very low risk of early rejection and good long-term allograft survival. By contrast, a positive virtual crossmatch is associated with a significant risk for early rejection and decreased allograft survival. However, these studies revealed that not all HLA-DSAs detected by SAFB have a detrimental clinical impact. The virtual crossmatch has emerged as a very useful tool for pretransplant risk assessment and organ allocation. Further advances of the virtual crossmatch approach will require improvements on the technical part of SAFB analysis and a better understanding and definition of pathogenic factors of HLA-DSA. Together with an extended HLA typing of the donor, this scenario will provide us the full benefits of applications based on virtual crossmatching.

Use of High-Dose Human Immune Globulin in Highly Sensitized Patients on the Kidney Transplant Waiting List: One Center's Experience

Introduction Transplant rates are low among highly sensitized patients with preformed anti-HLA antibodies, because of the additional immunologic barrier, the increased risk of rejection, and the greater chance of early graft loss. Intravenous infusion of pooled human immune globulin (IVIG) is immunomodulatory, neutralizing circulating antibodies and reducing rejection rates, two factors that may improve long-term transplantation outcomes. Methods We selected for high-dose IVIG treatment (1 g/kg monthly for 4 months) 10 adult, stage V, highly HLA-sensitized (PRA, historical >80% and current 56%–100%) chronic kidney disease patients listed for kidney transplantation with a mean waiting time of 7.5 years. They spanned age of 29–52 years. Anti-HLA titers were monitored monthly before each treatment and 1 month after the last IVIG dose; afterwards, patients were placed on an urgent list and followed for their transplant renal function and rejection episodes. Results Although 1 subject was transplanted after the first dose of IVIG, 9 patients completed the study, but their PRA decreased only insubstantially, namely, 14.4% (range, 8%–28%). During 6–12 months follow-up, 6 patients were considered for transplantation (negative crossmatch); 5 received kidneys and 1 was disqualified due to infection. The recipients were treated with antithymocyte globulin ( n = 3) or basiliximab ( n = 2) as well as tacrolimus/mycophenolate/steroids for baseline immunosuppression. Protocol biopsies (months 1, 3, and 6) in 4 patients (1 denied consent) revealed subclinical acute rejection and C4d positivity in most cases, either repeatedly or in the final biopsy. However at 6–12 months the mean serum creatinine concentration averaged 1.5 ± 0.4 mg/dL. Conclusion High-dose human IVIG reduced PRA poorly, but short-term transplantation outcomes were encouraging. Surveillance biopsies are advised for sensitized kidney recipients due to the frequent appearance of rejection, particularly of the antibody mediated type.