Human Leukocyte Antibody Research Articles

Pathogenetic analysis of transfusion-related acute lung injury caused by human leukocytes antigen antibody against human leukocyte antigen

From September 2019 to October 2020, pathogenetic analysis of three patients clinically diagnosed as transfusion-related acute lung injury (TRALI) caused by human leukocyte antibodies was conducted by Guangzhou Blood Centre, including 2 males and 1 female, aged 56, 50 and 20 years old, respectively. Solid phase agglutination, anti-human globulin test and flow cytometry method were used to detect the presence of antibodies against patients. Sequencing-based human leukocyte antigen (HLA-SBT) typing technique was used to detect the human leukocyte antigen (HLA) genotypes of patients. Lifecodes single antigen class Ⅰ/Ⅱ kit (LSA-Ⅰ/Ⅱ) were used to detect the specificity of HLA-class Ⅰ and class Ⅱ antibodies in donor blood by Luminex 200 liquid suspension chip system. The HLA specific antibodies and corresponding epitopes in donors were also analyzed. The results showed that HLA class Ⅰ or class Ⅱ specific antibodies against TRALI patients were detected in the blood donors. The plasma of donor 3 received by patient 1 contained antibodies against the patient's HLA-DRB1*09∶01 antigen, and the epitopes mediating the antibody reaction of the donor and recipient were 70R, 31I, 70QA. There were antibodies against the HLA-A*11∶02, HLA-A*11∶01, DRB1*12∶02, and DRB1*09∶01 antigens of patient 2 in the plasma of donor 4, and the associated antigenic epitopes were 151AHA, 57V, and 16Y. Antibodies against the HLA-DRB1*14∶04, DRB1*11∶01, and DPB1*05∶01 antigens of patient 3 were present in the plasma of donor 6 and donor 7, and the associated epitopes were 96HK, 140TV, 13SE, and 111K. Three cases of TRALI were confirmed to be caused by HLA antibodies through laboratory analysis, and human leukocyte antibody detection should be paid attention in clinically suspected cases of TRALI, and targeted diagnosis and treatment should be given.

Role of HLA in cardiothoracic transplantation.

In current clinical practice, transplant clinicians create collaborative working relationships with histocompatibility laboratory scientists to identify the risk of long-term graft failure, which may assist in establishing strategies for treatment and surveillance. Transplant immunology research also focuses on optimizing human leukocyte antibody tissue typing and defines the most effective test for detecting the presence of donor-specific antibodies. Although several studies have been conducted, data on pediatric heart transplant recipients are limited. Epitope load information may be utilized to identify donors with permissible human leukocyte antibody mismatches to increase transplant success. Although current guidelines do not consider human leukocyte antibody epitope-based matching tools, these guidelines could be useful for identifying recipients at a high risk of donor-specific antibody production, which would be appropriate for routine donor-specific antibody screening to initiate early interventions to prevent antibody-mediated rejection. Human leukocyte antibody matching at the epitope level offers an effective approach for identifying acceptable mismatches in sensitized patients and provides information about epitope loads. In the future, eplet matching may be used to define the best immunosuppressive therapy protocol for cardiothoracic organ transplantation. This report provides an overview of the role of human leukocyte antibodies in heart and lung transplantation.

Everolimus plus reduced calcineurin inhibitor prevents de novo anti-HLA antibodies and humoral rejection in kidney transplant recipients: 12-month results from the ATHENA study.

Studies prospectively monitoring de novo donor-specific antibodies (dnDSAs) and their clinical impact are sparse. This substudy of ATHENA was initiated to evaluate the effect of everolimus (EVR) or mycophenolic acid (MPA) in combination with reduced calcineurin inhibitor (CNI, tacrolimus [TAC] or cyclosporine [CsA]) on the formation of human leukocyte antibodies (HLA), including dnDSA, and the impact on clinical outcomes in kidney transplant (KTx) recipients. All eligible patients were randomized 1:1:1 to receive either EVR + TAC, EVR + CsA or MPA + TAC, with basiliximab induction plus steroids after transplantation up to Month 12. The incidence of dnDSA by treatment group and the association with clinical events were evaluated descriptively as an exploratory objective in the intent-to-treat (ITT) and per-protocol (PP) populations with at least one antibody assessment. Overall, none of the patients in the EVR + TAC group had either dnDSA or antibody mediated rejection (PP or ITT population) and only one patient with dnDSA in the TAC + MPA group had antibody mediated rejection. The EVR regimen was comparable to MPA regimen with an extremely low incidence of dnDSA over 1 year of treatment.

(742) Prognostic Value of Donor Specific Human Leukocyte Antibodies in Pre-Sensitized Heart Transplant Patients

(742) Prognostic Value of Donor Specific Human Leukocyte Antibodies in Pre-Sensitized Heart Transplant Patients

Recruitment Strategy for Potential COVID-19 Convalescent Plasma Donors

Recruitment Strategy for Potential COVID-19 Convalescent Plasma Donors

The Role of Human Leukocyte Antigen Sensitization as a Risk Factor for Mortality in Patients Bridged to Heart Transplantation with VA-ECMO

Patients bridged to heart transplantation (BTT) with VA-ECMO have increased mortality in the first post-transplant year. This has been observed even after robust adjustment for recipient and donor comorbidities, suggesting either residual unmeasured risk or possible exacerbation of risk in the VA-ECMO BTT patient. Human leukocyte antibody (HLA) sensitization is observed more frequently with mechanical circulatory support. We hypothesize an increased risk of mortality in VA-ECMO BTT as a function of HLA sensitization. We analyzed all 27,495 adult patients in the United Network for Organ Sharing database who underwent heart transplantation between 6/30/2004 and 12/30/2018, excluding re-transplantation or multiple organ transplantation. HLA sensitization was assessed by panel reactive antibody (direct or calculated). Odds of early graft failure (within 48 hours) or acute rejection (during the index hospitalization), hazard of all-cause mortality, and cause-specific relative hazard (csRH) of graft failure were modeled with pre-transplant VA-ECMO with and without PRA. Models were adjusted for recipient, donor, and operative risk factors including center and transplant year. VA-ECMO was used as BTT in 176 patients (0.64%), who were younger than those without VA-ECMO (mean age 44 vs 53, p<0.001) but with similar sex and ethnicity. VA-ECMO BTT patients had higher PRA (p=0.003) and more frequently had PRA>20% (18% vs 12%, p=0.034). After risk adjustment, VA-ECMO patients had more early graft failure (OR 5.6; 95% 2.2, 14.5), shorter time to graft failure (csRH 3.6; 2.1,6.2), and shorter time to mortality (HR 3.5; 2.6, 4.7), but no difference in acute rejection. PRA was independently associated with early graft failure (OR 1.09 per 10%; 1.01, 1.18), acute rejection (1.07; 1.04, 1.09), time to graft failure (1.05; 1.0, 1.09), and time to mortality (1.03; 1.01, 1.06), but did not modify the association between VA-ECMO and mortality (HR 1.1; 0.99, 1.3). VA-ECMO as BTT is independently associated with higher odds of early graft failure, shorter time to graft failure, and shorter time to all-cause mortality. HLA sensitization is independently associated with the same outcomes and with acute rejection, but with a small effect size. HLA sensitization did not modify the association of VA-ECMO with outcomes.

Class I and II human leukocyte antibodies in pediatric haploidentical allograft candidates: prevalence and risk factors.

Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) were associated with graft failure (GF) following haploidentical stem cell transplantation (Haplo-HSCT). The prevalence and risk factors of DSAs in pediatric candidates remain to be determined. In a prospective trial (ChiCTR-OPC-15006672), 486 children with hematological diseases were enrolled to screen for the presence of anti-HLA class I and II antibodies of immunoglobulin G type. Fifty two patients (10.7%) demonstrated positive panel-reactive antibody (PRA) for class I; 24 (4.9%), for class II; and 13 (2.7%), for both. Multivariate analysis showed diagnosis was the independent risk factor for antibodies, as acute lymphoblastic leukemia (ALL) patients (HR0.141, 95% CI: 0.037-0.538, p = 0.004) had a lower incidence of class II PRAs and DSAs against HLA-B, DQ, and DR, whereas myelodysplastic syndrome (MDS) patients had a higher incidence of PRAs for both class I and class II (HR4.790, 95% CI: 1.010-22.716, p = 0.049), and DSAs against HLA-A, B, C, DP, and DQ. Older age (>12 vs. ≤12) was associated with DSAs against HLA-DP (HR0.194, 95% CI: 0.041-0.918, p = 0.039). Our findings provided novel evidence for prevalence and risk factors for PRAs and DSAs in pediatric candidates receiving haplo-HSCT, possibly benefiting anti-HLA antibody monitoring and donor selection.

Impact of transplant accessibility for sensitized patients by avoiding unacceptable antigens.

Recent data have confirmed the negative impact of preformed donor-specific antibodies (pDSAs) after liver transplantation (LT). In order to reduce the risk of developing lesions associated with acute and chronic antibody-mediated rejection in LT recipients, we evaluated the consequences in terms of transplant accessibility, associated with avoiding pDSAs according to several mean fluorescence intensity (MFI) titer thresholds that have been previously reported to be relevant in LT. Among the 484 included LT candidates, 99 (20.5%) presented with anti-human leukocyte antibodies (HLAs). The predictive factors for anti-HLA sensitization were a history of previous kidney transplantation (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.30-1.9; P = 0.05), a history of previous LT (OR, 1.9; 95% CI, 1.6-2.1; P = 0.01), a history of blood transfusion (OR, 2.5; 95% CI, 2.2-4.1; P = 0.01), and a history of pregnancy (OR, 2.9; 95% CI, 2.4-3.3; P = 0.04). By applying a strategy of unacceptable mismatches for recipients with an antibody (Ab) MFI of > 5000, only 35 patients were affected (7% of the cohort), but 22 of these (63%) would have been considered incompatible with >50% of the donors. Using a MFI threshold of >10,000, only 16 patients were affected (1.4% of the cohort), but half of these would have been considered incompatible with >50% of the proposed donors. Considering only those with anti-class II Ab and a MFI >5000 and >10,000, respectively, 10/14 and 4/8 patients were considered incompatible with >50% of the donors. In conclusion, avoiding pDSAs affects a small but not negligible proportion of LT candidates. However, in these sensitive patients, avoiding pDSAs has the potential to significantly reduce the donor pool and, consequently, transplant accessibility. Liver Transplantation 23 880-886 2017 AASLD.

Early Vascular Thrombosis After Kidney Transplantation: Can We Predict Patients at Risk?

BackgroundRenal transplant is the therapy of choice for patients with chronic renal disease. In recent years, improvement in immunosuppressive drugs reduced early graft loss associated with acute rejection. However, vascular thrombosis, accounting for 5% of early graft loss, can sensitize the recipient for human leukocyte antibodies, reducing the chance for a second transplant. The aim of this study was to identify risk factors for vascular thrombosis in a single transplant center, to design specific prevention protocol. MethodsThis was a retrospective, case-control study. From the Renal Transplant Unit database, we identified 21 cases of vascular thrombosis in recipients of kidneys from deceased donors. Recipients from the contralateral kidney from the same donor, without vascular complications, were assigned to the control group. Data analyzed included donor, recipient, transplant surgery, and post-operative follow-up. The local ethics committee approved the protocol. ResultsThrombosis and control groups were comparable for recipient characteristics, cold ischemia time, organ side (right or left), and site of arterial anastomosis. We observed an increased risk for vascular thrombosis in kidneys with multiple veins (odds ratio, 11.32; P = .03). Organ retrieval surgery complications, such as vascular lesions or heterogeneous perfusion, despite normal pre-implantation biopsy, were considered risk factors for vascular thrombosis within the first post-operative day (odds ratio, 7.1; P = .03). ConclusionsIn this series, multiple renal vein and organ retrieval surgery complications were risk factors for early vascular thrombosis.

A Case Report of Transfusion-Related Acute Lung Injury Induced in the Patient with HLA Antibody after Fresh Frozen Plasma Transfusion

Development of transfusion-related acute lung injury (TRALI), a non-cardiogenic pulmonary edema, after blood transfusion, is a rare but potentially leading cause of mortality from blood transfusion. We report on a case of TRALI in a 51-year male with acute calculous cholecystitis and liver cirrhosis. As preoperative treatment, he was given ten units of fresh frozen plasma (FFP) for 3 days before the operation. During the transfusion of the 10th unit of FFP, he experienced a sudden onset of hemoptysis, tachypnea, tachycardia, and cyanosis. Bilateral pulmonary infiltration not observed on the chest X-ray at the visit was newly developed. There was no evidence of volume overload but severe hypoxemia. Blood transfusion was stopped and he recovered fully after 8 days of oxygen therapy through a nasal cannula. Although HLA and HNA antibodies were not detected in the donor's blood, HLA antibodies (A2, B57, B58) were detected in the patient's blood. We reported this meaningful case of TRALI that occurred after transfusion of only fresh frozen plasma which did not contain human leukocyte antibody in a patient with HLA antibody. (Korean J Blood Transfus 2015;26:309-315)

Changes in the methodology of pre-heart transplant human leukocyte antibody assessment: an analysis of the United Network for Organ Sharing database.

We sought to investigate temporal trends in the methodology of human leukocyte antibody assessment in heart transplantation. The United Network for Organ Sharing database was queried from June 2004 to March 2013 to obtain pre-heart transplantation human leukocyte antibody results. The % panel reactive antibody for class I and II antibodies was recorded along with the methodology of assessment. Allosensitization was defined as class I and/or II panel reactive antibody of ≥ 10%. The primary outcome measure was graft survival. During the study period, 12,858 patients with available data underwent heart transplantation. The prevalence of allosensitization increased, with 16.8% in 2005-2006 sensitized at the time of transplantation compared to 23.1% in 2010-2011 (p < 0.001); this occurred in conjunction with an increase in the utilization of flow cytometry (77.2% in 2005-2006; 97.0% in 2010-2011, p < 0.001). Using multivariable analysis, a positive pre-heart transplantation panel reactive antibody by flow cytometry independently predicted graft loss. There has been a recent increase in flow cytometric assessment of human leukocyte antibodies prior to heart transplantation, which may be associated with an increase in the prevalence of pre-transplant patients being characterized as allosensitized. Flow cytometry may identify patients with the highest likelihood of graft loss.

Antibody-mediated rejection in liver transplantation: Current controversies and future directions

Interest in the role of donor-specific human leukocyte antibodies in liver transplantation has been rekindled recently. Emerging evidence suggests that these antibodies may cause injury to the liver allograft. Here we review the clinical literature, highlight controversial results, and propose a path forward for the definition and better understanding of antibody-mediated injury to the liver.

Beneficial or Harmful Effect of Antipaternal Human Leukocyte Antibodies on Pregnancy Outcome? A Systematic Review and Meta‐Analysis

During pregnancy, antibodies are induced that target the paternal human leukocyte antigens of the semi-allogeneic fetus. The level and presence of these antibodies have been reported increased as well as decreased for a variety of pregnancy complications; the clinical relevance and consequences of these antibodies are not very clear. Therefore, the objective of this review is to determine whether the presence of antipaternal antibodies influences pregnancy outcome. We performed a systematic search of studies that described the effect of antipaternal antibodies on pregnancy complications. The primary outcome was the risk ratio for HLA class I and class II antibodies on pregnancy complications. Furthermore, we calculated the risk for first- and third-trimester complications. The seventeen studies that were selected for meta-analysis showed high level of statistical and clinical heterogeneity. In the meta-analysis, we found no significant effect of HLA class I or class II antibodies on pregnancy outcome. No consistent conclusions can be drawn from the meta-analysis. Discrepancies in the meta-analysis are the result of different screening techniques, varying time points of screening, and use of incorrect control groups. Furthermore, more detailed analyses of the characteristics and specificity of the antibodies involved are essential.

Abstract 19129: Clinically Important Human Leukocyte Antibody Production is Uncommon in a Large Series of Pediatric Patients Supported with the Berlin Heart EXCOR Ventricular Assist Device

Background: Ventricular assist device (VAD) support is associated with human leukocyte (HLA) antibody production. This process, known as sensitization, has not been evaluated in pediatric patients supported with the Berlin Heart EXCOR VAD. Furthermore, the impact of sensitization in the era of single antigen assays for the detection of HLA antibodies is unclear. Methods: The records of all patients supported with a Berlin Heart EXCOR VAD at our institution from 4/2005-8/2011 were reviewed. Class I and II HLA antibodies were identified by fluorescence methods pre-/post-VAD, with antibody titer reported as median fluorescence intensity (MFI). MFIs were summed to derive a total MFI for each patient post-VAD. To determine changes in HLA antibodies pre-/post-VAD, MFIs pre-VAD were compared with those ≥14 days post-VAD, but prior to transplant, using Wilcoxon matched-pairs sign-rank test. Sensitization was present if MFI for any antibody was &gt; 1000 (threshold for a positive flow cytometric crossmatch). Results: The Berlin Heart EXCOR VAD was used in 36 patients; 20 met inclusion criteria and 13 had complete MFI data. Median duration of support was 56 (21 - 131) days; all survived to transplant. For the entire group, changes in total MFI for class I and class II HLA antibodies were not significant over the course of VAD therapy. For class I antibodies, 6/13 (46%) were sensitized pre-VAD, and 7/13 (54%) were so for class II antibodies; sensitization was maintained for the same antibodies in 4/6 for class I antibodies and 5/7 for class II antibodies. De novo sensitization, including new antibodies in presensitized patients, occurred in 9/13 (69%) for class I antibodies and 4/13 (31%) for class II antibodies. Only one patient, however, had a positive flow cytometric crossmatch at transplant to one class II HLA antibody that developed on VAD. No patient was denied an acceptable donor heart on the basis of elevated HLA antibodies. Conclusions: Using single antigen techniques, HLA sensitization is seen in approximately 50% of pediatric patients prior to initiating support with the Berlin Heart EXCOR VAD; nearly 70% developed de novo class I HLA antibodies on VAD. The clinical impact of such antibodies, however, appears to be limited in this population.

The Detection of Serum Hla Antibodies by Luminex Bead Assays Can Be Improved by the Addition of Edta or Dithiotreitol

The detection and specification of human leukocyte antibodies (HLA antibodies) has improved in the recent years through the introduction of solid phase techniques. The Luminex x-MAP technology with single HLA antigen coated beads allows a more precise and reproducible specification of HLA antibodies than cell based methods or ELISA using antigen extracts from cells. However, there are some drawbacks. The sensitivity is very high and the correlation of the results with clinical data and standard test systems like the complement dependent cytotoxicity (CDC) assay is not always satisfactory. Recently it has been shown, that Luminex-based HLA antibody assays might be disturbed by prozone phenomena resulting from binding of C1q and/or IgM, when sera with a high content of HLA antibodies are analyzed. Dilution, treatment of the sera with DTT or addition of EDTA seem to decrease these effects but may have marked influences on the results of these assays. We tested sera from five highly immunized patients for in CDC (for HLA-Class I antibodies), LABScreen Mixed and LABScreen single antigen tests (for HLA-Class I and II antibodies) using untreated, DTT-treated serum or serum supplemented with 8 mM EDTA. 4 CDC (-/+DTT) positive sera showed a high increase (DTT>EDTA) in reaction strengths for some HLA specificities, which was more pronounced for the antibody specificities reactive in CDC. DTT or EDTA treatment changed the number of HLA antibody specificities detected to a variable extent in all five sera. The CDC negative serum showed minor changes in reaction strength. The signal strenghs of the different specificities mainly remained in the order of the untreated serum. In summary Luminex bead assay systems are sensitive to prozone phenomena which might be diminished by DTT treatment or addition of EDTA. By using these methods a further increase of sensitivity and a change of detected specificities with results differing from the results with untreated sera have to be expected. However, the use of DTT or EDTA might improve the results. In our cases we found, that specificities confirmed by data from the immunizer and/or found in the CDC-assay are better represented in the results. Further efforts should be taken to verify, if one of these methods could replace the regular Luminex bead assay with untreated serum.

Transfusion-related acute lung injury: Current understanding and preventive strategies

Transfusion-related acute lung injury (TRALI) is the most serious complication of transfusion medicine. TRALI is defined as the onset of acute hypoxia within 6hours of a blood transfusion in the absence of hydrostatic pulmonary oedema. The past decades have resulted in a better understanding of the pathogenesis of this potentially life-threating syndrome. The present notion is that the onset of TRALI follows a threshold model in which both patient and transfusion factors are essential. The transfusion factors can be divided into immune and non-immune mediated TRALI. Immune-mediated TRALI is caused by the passive transfer of human neutrophil antibodies (HNA) or human leukocyte antibodies (HLA) present in the blood product reacting with a matching antigen in the recipient. Non-immune mediated TRALI is caused by the transfusion of stored cell-containing blood products. Although the mechanisms behind immune-mediated TRALI are reasonably well understood, this is not the case for non-immune mediated TRALI. The increased understanding of pathways involved in the onset of immune-mediated TRALI has led to the design of preventive strategies. Preventive strategies are aimed at reducing the risk to exposure of HLA and HNA to the recipient of the transfusion. These strategies include exclusion of “at risk” donors and pooling of high plasma volume products and have shown to reduce the TRALI incidence effectively. This review discusses the current understanding of TRALI and preventive strategies available.

597 Persistence of Human Leukocyte Antibodies in Congenital Heart Disease Late Following Surgery Utilizing Allograft and Whole Blood

Allograft is used for aortic arch reconstruction in hypoplastic left heart syndrome (HLHS) and vascular reconstruction in cavopulmonary connections (Glenn). Although allograft induces human leukocyte (HLA) antibody formation, the nature of this response, its duration beyond 5 years (y), and the role of blood transfusion are unknown.

819 Human Leukocyte Antibody Production Is Uncommon in a Large Series of Pediatric Patients Supported with the Berlin Heart EXCOR Ventricular Assist Device

819 Human Leukocyte Antibody Production Is Uncommon in a Large Series of Pediatric Patients Supported with the Berlin Heart EXCOR Ventricular Assist Device

Human Umbilical Cord Blood Mononuclear Cells Decrease Fibrosis and Increase Cardiac Function in Cardiomyopathy

We investigated whether human umbilical cord blood mononuclear cells (HUCBC) can limit progressive cardiomyopathy in TO2 hamsters. A total of 22 TO2 1-month-old hamsters were treated with intramyocardial HUCBC, 4 x 10(6) in Isolyte, and 23 TO2 1-month-old hamsters were treated with intramyocardial Isolyte. A total of 16 1-month-old F1B hamsters served as controls and received intramyocardial Isolyte. Echocardiograms were performed on all hamsters prior to and monthly after treatment for 6 months. Heart tissues were then stained with hematoxylin and eosin, Masson's Trichrome and human leukocyte antibody. In F1B hamsters, left ventricular fractional shortening (FS) and ejection fractions (EF) did not significantly decrease over 6 months. By contrast, in Isolyte-treated TO2 hamsters, FS decreased from 56.2 +/- 1.0% to 19.7 +/- 3.2% and EF decreased from 89.5 +/- 1.4% to 44.9 +/- 5.9% at 6 months (both p < 0.0001). The FS and EF in HUCBC-treated TO2 hamsters also progressively decreased over 6 months but the changes were more gradual, especially during the first month after HUCBC treatment when FS was 52.0 +/- 1.5% and EF was 89.5 +/- 1.4%, which was not significantly different from the FS and EF in the F1B hamsters. Moreover, in the HUCBC-treated hamsters, the FS and EF were 20-30% greater than FS and EF in Isolyte TO2 hamsters at 3 and 5 months (p < 0.01). In Isolyte-treated TO2 hamsters at 6-7 months, fibrosis involved 30.0 +/- 5.0% of left ventricle and 35.0 +/- 5.0% of septum. By contrast, in HUCBC-treated hamsters, fibrosis involved only 6.5 +/- 2.3% of the left ventricle and 6.3 +/- 1.8% of septum (p < 0.05). The average number of blood vessels per myocardial microscopic field in HUCBC-treated hearts was 53.5 +/- 0.8 versus 46.2 +/- 3.0 in Isolyte-treated TO2 hearts (p < 0.05). HUCBC, when given as a single intramyocardial injection, can limit fibrosis and increase heart function over the short term in TO2 hamsters with cardiomyopathy.

Fate of the Mate: The Influence of Delayed Graft Function in Renal Transplantation on the Mate Recipient

Delayed graft function (DGF) in a deceased-donor renal recipient is associated with allograft dysfunction 1-year posttransplant. There is limited research about the influence to allograft function on the mate of a DGF recipient over time. Using a retrospective cohort design, we studied 55 recipients from a single center. The primary outcome was the change in glomerular filtration rate (GFR) 1-year posttransplant. The secondary outcome was the GFR at baseline. We found that mates to DGF recipients had a mean change in GFR 1-year posttransplant of -11.2 mL/min, while the control group had a mean change of -0.4 mL/min. The difference in the primary outcome was significant (p = 0.025) in a multivariate analysis, adjusting for cold ischemic time, panel reactive antibody level, allograft loss, human leukocyte antibody (HLA)-B mismatches and HLA-DR mismatches. No significant difference between groups was found in baseline GFR. In conclusion, mates to DGF recipients had a significantly larger decline in allograft function 1-year posttransplant compared to controls with similar renal function at baseline. We believe strategies that may preserve allograft function in these'at-risk'recipients should be developed and tested.