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Given the risk of rejection, the presence of preformed donor specific antibodies (DSA) contraindicates transplantation in most allocation systems. However, HLA-Cw and -DP DSA escape this censorship. We performed a multicentric observational study, in which the objective was to determinate risk factors of acute antibody-mediated rejection (aABMR) in recipients transplanted with preformed isolated Cw- or DP-DSA. Between 2010 and 2019, 183 patients were transplanted with a preformed isolated Cw- or DP-DSA (92 Cw-DSA; 91 DP-DSA). At 2 years, the incidence of aABMR was 12% in the Cw-DSA group, versus 28% in the DP-DSA group. Using multivariable Cox regression model, the presence of a preformed DP-DSA was associated with an increased risk of aABMR (HR = 2.32 [1.21-4.45 ( p = 0.001)]) compared with Cw-DSA. We also observed a significant association between the DSA's MFI on the day of transplant and the risk of aABMR (HR = 1.09 [1.08-1.18], p = 0.032), whatever the DSA was. Interaction term analysis found an increased risk of aABMR in the DP-DSA group compared with Cw-DSA, but only for MFI below 3,000. These results may plead for taking these antibodies into account in the allocation algorithms, in the same way as other DSA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Laboux, Lenain, Visentin, Flahaut, Chamley, Provôt, Top, Kerleau, Labalette, Choukroun, Couzi, Blancho, Hazzan and Maanaoui.)

Alloimmune responses in kidney transplant (KT) patients previously hospitalized with COVID-19 are understudied. We analyzed a cohort of 112 kidney transplant recipients who were hospitalized following a positive SARS-CoV-2 test result during the first 20 months of the COVID-19 pandemic. We found a cumulative incidence of 17% for the development of new donor-specific antibodies (DSA) or increased levels of pre-existing DSA in hospitalized SARS-CoV-2-infected KT patients. This risk extended 8 months post-infection. These changes in DSA status were associated with late allograft dysfunction. Risk factors for new or increased DSA responses in this KT patient cohort included the presence of circulating DSA pre-COVID-19 diagnosis and time post-transplantation. COVID-19 vaccination prior to infection and remdesivir administration during infection were each associated with decreased likelihood of developing a new or increased DSA response. These data show that new or enhanced DSA responses frequently occur among KT patients requiring admission with COVID-19 and suggest that surveillance, vaccination, and antiviral therapies may be important tools to prevent alloimmunity in these individuals., Competing Interests: EL receives research support from Amgen and consults for Novartis. AN serves on the scientific advisory board of Janssen. JL, PP, and BO receive grant salary support from Lung Biotechnology PBC, a subsidiary of United Therapeutics. GB receives consulting fees from Med-IQ, research support from Merck Foundation, and an honorarium from StateServ. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Killian, Houp, Burkholder, Roman Soto, Killian, Ong, Erdmann, Goepfert, Hauptfeld-Dolejsek, Leal, Zumaquero, Nellore, Agarwal, Kew, Orandi, Locke, Porrett, Levitan, Kumar and Lund.)

Anti-HLA Donor Specific Antibody (DSA) detection post kidney transplant has been associated with adverse outcomes, though the impact of early DSA screening on stable patients remain unclear. We analyzed impact of DSA detection through screening in 1st year stable patients ( n = 736) on subsequent estimated glomerular filtration rate (eGFR), death censored graft survival (DCGS), and graft failure (graft loss including return to dialysis or re-transplant, patient death, or eGFR < 20 ml/min at last follow up). Patients were grouped using 1st year screening into DSA+ (Class I, II; n = 131) or DSA- ( n = 605). DSA+ group were more DR mismatched ( p = 0.02), more sensitized (cPRA ≥90%, p = 0.002), less Caucasian ( p = 0.04), and had less pre-emptive ( p = 0.04) and more deceased donor transplants ( p = 0.03). DSA+ patients had similar eGFR (54.8 vs. 53.8 ml/min/1.73 m 2 , p = 0.56), DCGS (91% vs. 94%, p = 0.30), and graft failure free survival (76% vs. 82%, p = 0.11). DSA timing and type did not impact survival. Among those with a protocol biopsy ( n = 515), DSA detected on 1st year screening was a predictor for graft failure on multivariate analysis (1.91, 95% CI 1.03-3.55, p = 0.04). Overall, early DSA detection in stable patients was an independent risk factor for graft failure, though only among those who underwent a protocol biopsy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sharma, Jorgensen, Mehta, Sood, Puttarajappa, Wu, Tevar, Molinari, Zeevi and Hariharan.)

Reduced immunosuppression during BKV-DNAemia has been associated with T-cell mediated rejection (TCMR), de novo donor-specific antibodies (DSA) and antibody-mediated rejection (ABMR). Intravenous immunoglobulins (IVIG) may reduce alloimmunity. We studied 860 kidney transplant recipients (KTRs) for the development of BKV-DNAuria and BKV-DNAemia (low-level <10 000 IE/ml, high-level >10 000 IE/ml). 52/131 KTRs with high-level BKV-DNAemia received IVIG. The HLA-related immunological risk was stratified by the Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) algorithm. BKV-DNAuria only was observed in 86 KTRs (10.0%), low-level BKV-DNAemia in 180 KTRs (20.9%) and high-level BKV-DNAemia in 131 KTRs (15.2%). KTRs with low-level BKV-DNAemia showed significantly less TCMR compared to KTRs with high-level BKV-DNAemia (5.2% vs. 25.5%; P < 0.001) and no BKV-replication (13.2%; P = 0.014), lowest rates of de novo DSA (21.3%), ABMR (9.2%) and flattest glomerular filtration rate (GFR) slope (-0.8 ml/min). KTRs with low-level BKV-DNAemia showed significantly higher median (interquartile range) total PIRCHE if they developed TCMR [100.22 (72.6) vs. 69.52 (49.97); P = 0.020] or ABMR [128.86 (52.99) vs. 69.52 (49.96); P = 0.005]. Administration of IVIG did not shorten duration of BKV-DNAemia (P = 0.798) or reduce TCMR, de novo DSA and ABMR (P > 0.05). KTRs with low-level BKV-DNAemia showed best protection against alloimmunity, with a high number of PIRCHE co-determining the remaining risk. The administration of IVIG, however, was not beneficial in reducing alloimmunity., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Between 2000 and 2014, five patients received bilateral hand (n = 3), bilateral forearm (n = 1), and unilateral hand (n = 1) transplants at the Innsbruck Medical University Hospital. We provide a comprehensive report of the long-term results at 20 years. During the 6-20 years follow-up, 43 rejection episodes were recorded in total. Of these, 27.9% were antibody-related with serum donor-specific alloantibodies (DSA) and skin-infiltrating B-cells. The cell phenotype in rejecting skin biopsies changed and C4d-staining increased with time post-transplantation. In the long-term, a change in hand appearance was observed. The functional outcome was highly depending on the level of amputation. The number and severity of rejections did not correlate with hand function, but negatively impacted on the patients´ well-being and quality of life. Patient satisfaction significantly correlated with upper limb function. One hand allograft eventually developed severe allograft vasculopathy and was amputated at 7 years. The patient later died due to progressive gastric cancer. The other four patients are currently rejection-free with moderate levels of immunosuppression. Hand transplantation remains a therapeutic option for carefully selected patients. A stable immunologic situation with optimized and individually adopted immunosuppression favors good compliance and patient satisfaction and may prevent development of DSA., (© 2020 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

Donor-specific antibodies (DSA) cause antibody-mediated rejection (AMR); however, their pathogenic role has not yet been adequately investigated after liver transplantation. The aim of our study was to analyse the clinical significance of DSA and complement-binding DSA for the prediction of AMR after liver transplantation. Our cohort included 120 liver recipients with assessed protocol biopsies one year post-transplant. All patients had defined HLA-specific and complement-binding (C1q + and C3d+) antibodies before and in regular intervals after transplantation. The incidence of DSA was evaluated in relation with clinical and histopathological data in the liver allografts. A higher occurrence of acute AMR was observed in recipients with preformed complement-binding DSA to HLA Class I antigens. Patients who developed chronic AMR had more frequently de novo-produced antibodies against HLA Class II antigens (P = 0.0002). A correlation was also found between de novo-formed C1q + and C3d+-binding antibodies to HLA Class II antigens and the development of chronic AMR (P = 0.043). Our study implies that preformed complement-binding DSA to HLA Class I antigens are related to increased risk of acute antibody-mediated rejection, while chronic AMR is more frequent in patients with de novo-produced antibodies to HLA Class II antigens after liver transplantation., (© 2020 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Anti-HLA-antibody characteristics aid to risk-stratify patients and improve long-term renal graft outcomes. Complement activation by donor-specific antibody (DSA) is an important characteristic that may determine renal allograft outcome. There is heterogeneity in graft outcomes within the moderate to high immunological risk cases (cross-match-positive). We explored the role of C3d-positive DSAs in sub-stratification of cross-match-positive cases and relate to the graft outcomes. We investigated 139 cross-match-positive living-donor renal transplant recipients from four transplant centres in the United Kingdom. C3d assay was performed on serum samples obtained at pretreatment (predesensitization) and Day 14 post-transplant. C3d-positive DSAs were found in 52 (37%) patients at pretreatment and in 37 (27%) patients at Day 14 post-transplant. Median follow-up of patients was 48 months (IQR 20.47-77.57). In the multivariable analysis, pretreatment C3d-positive DSA was independently associated with reduced overall graft survival, the hazard ratio of 3.29 (95% CI 1.37-7.86). The relative risk of death-censored five-year graft failure was 2.83 (95% CI 1.56-5.13). Patients with both pretreatment and Day 14 C3d-positive DSAs had the worst five-year graft survival at 45.5% compared with 87.2% in both pretreatment and Day 14 C3d-negative DSA patients with the relative risk of death-censored five-year graft failure was 4.26 (95% CI 1.79, 10.09). In this multicentre study, we have demonstrated for the first time the utility of C3d analysis as a distinctive biomarker to sub-stratify the risk of poor graft outcome in cross-match-positive living-donor renal transplantation., (© 2020 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

There is a dearth of published data regarding the presence of post-transplant donor-specific antibodies (DSA), especially C1q-binding DSA (C1q+DSA), and patient and kidney allograft outcomes in simultaneous liver-kidney transplant (SLKT) recipients. We conducted a retrospective cohort study consisted of 85 consecutive SLKT patients between 2009 and 2018 in our center. Associations between presence of post-transplant DSA, including persistent and/or newly developed DSA and C1q+DSA, and all-cause mortality and the composite outcome of mortality, allograft kidney loss, and antibody-mediated rejection were examined using unadjusted and age and sex-adjusted Cox proportional hazards and time-dependent regression models. The mean age at SLKT was 56 years and 60% of the patients were male. Twelve patients (14%) had post-transplant DSA and seven patients (8%) had C1q+DSA. The presence of post-transplant DSA was significantly associated with increased risk of mortality (unadjusted model: Hazard Ratio (HR) = 2.72, 95% confidence interval (CI): 1.06-6.98 and adjusted model: HR = 3.20, 95% CI: 1.11-9.22) and the composite outcome (unadjusted model: HR = 3.18, 95% CI: 1.31-7.68 and adjusted model: HR = 3.93, 95% CI: 1.39-11.10). There was also higher risk for outcomes in recipients with C1q+DSA compared the ones without C1q+DSA. Post-transplant DSA is significantly associated with worse patient and kidney allograft outcomes in SLKT. Further prospective and large cohort studies are warranted to better assess these associations., (© 2019 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

Recognition of non-self structures on donor cells represents the main immunological barrier in solid organ transplantation. The human leukocyte antigens (HLA) are considered the most important non-self (allo)antigens in transplantation. Long-term graft attrition is mainly caused by the formation of alloreactive antibodies that are directed against non-self structures (i.e., epitopes) on cell surface proteins. Recently published data provided evidence for a similar importance of non-HLA mismatches between donors and recipients in acute rejection as well as long-term kidney allograft survival. These data suggest a broader concept of immunological non-self that goes beyond HLA incompatibility and expands the current concept of polymorphic non-self epitopes on cell surface molecules from HLA to non-HLA targets. Amino acid substitutions caused by single nucleotide variants in protein-coding genes or complete loss of gene expression represent the basis for polymorphic residues in both HLA and non-HLA molecules. To better understand these novel insights in non-HLA alloimmunity, we will first review basic principles of the alloimmune response with a focus on the HLA epitope concept in donor-specific antibody formation before discussing key publications on non-HLA antibodies., (© 2019 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

In this review, we discuss a possible central role of T-cell help in severe forms of graft damage mediated by donor-specific HLA antibodies (DSA). Some kidney transplant recipients with pretransplant DSA show a high graft failure rate, whereas in other patients DSA do not harm the transplanted kidney and in most cases, disappear shortly after transplantation. Analyzing 80 desensitized highly immunized kidney transplant recipients and another multicenter cohort of 385 patients with pretransplant HLA antibodies, we reported recently that an ongoing T-cell help from an activated immune system, as measured by an increased level of soluble CD30 in serum, might be necessary for the DSA to exert a deleterious effect. Patients positive for both pretransplant DSA and sCD30 appear to require special measures, such as the elimination of DSA from the circulation, potent immunosuppression, good HLA-matching, and intense post-transplant monitoring, whereas exclusion of DSA-positive patients from transplantation in the absence of high sCD30 may not be justified in all cases, even if the pretransplant DSA are strong and complement-activating., (© 2018 Steunstichting ESOT.)

Data related to graft outcomes following post-transplant lymphoproliferative disease (PTLD) in pediatric kidney transplantation are scarce. Data were analyzed retrospectively from 12 children (eight boys) for 3 years after diagnosis of PTLD, with a loss of follow-up after 2 years in two of 12. In all cases, intensity of immunosuppressive therapy was reduced, which switched from calcineurin inhibitor to a mammalian target of rapamycin (mTOR) inhibitor in ten cases. Nine children were treated with six doses of rituximab according to the PED-PTLD-2005 protocol, with additional treatment in one child as per protocol. One patient received EuroNet-PHL C1. In four patients, donor-specific antibodies were detected after PTLD diagnosis at 3, 4, 5 and 7 years, respectively. One patient developed chronic antibody-mediated rejection (cAMR) 12 years after diagnosis, losing the graft 1 year later. Three patients with recurrence of the original disease also lost their grafts, one at the time of diagnosis of PTLD, and two after 4 years. Range-based analysis of variance showed that there was no decrease in estimated GFR at 1, 2, or 3 years after diagnosis of PTLD (P = 0.978). In conclusion, treatment of PTLD with reduced immunosuppression is safe and efficient. This may be due to B-cell-depleting therapy of PTLD with rituximab., (© 2017 Steunstichting ESOT.)

Combining vascularized composite allotransplantation (VCA) with intestinal transplantation to achieve primary abdominal closure has become a feasible procedure. Besides facilitating closure, the abdominal wall can be used to monitor intestinal rejection. As the inclusion of a VCA raises the possibility of an enhanced alloimmune response, we investigated the incidence and clinical effect of de novo donor-specific HLA antibodies (dnDSA) in a cohort of patients receiving an intestinal transplant with or without a VCA. The sequential clinical study includes 32 recipients of deceased donor intestinal and VCA transplants performed between 2008 and 2015; eight (25%) modified multivisceral transplants and 24 (75%) isolated small bowel transplants. A VCA was used in 18 (56.3%) cases. There were no episodes of intestinal rejection without VCA rejection. Fourteen patients (14 of 29; 48.3%) developed dnDSA. In the VCA group, fewer patients developed dnDSA; six of 16 (37.5%) VCA vs. eight of 13 (61.5%) non-VCA. There was no statistically significant difference in one- and 3-year overall graft survival stratified for the presence of dnDSA; P = 0.286. In the study, there is no evidence that the addition of a VCA increases the incidence of dnDSA formation compared to transplantation of the intestine alone., (© 2017 Steunstichting ESOT.)

Detrimental impact of preformed donor-specific antibodies (DSAs) against human leucocyte antigens on outcomes after kidney transplantation are well documented, however, the value of their capacity to bind complement for predicting antibody-mediated rejection (AMR) and graft survival still needs to be confirmed. We aimed to study DSA characteristics (strength and C1q binding) that might distinguish harmful DSA from clinically irrelevant ones. We retrospectively studied 60 kidney-transplanted patients with preformed DSA detected by single antigen bead (SAB) assays (IgG and C1q kits), from a cohort of 517 kidney graft recipients (124 with detectable anti-HLA antibodies). Patients were divided into DSA strength (MFI < vs. ≥ 15 000) and C1q-binding ability. AMR frequency was high (30%) and it increased with DSA strength (P = 0.002) and C1q+ DSA (P < 0.001). The performance of DSA C1q-binding ability as a predictor of AMR was better than DSA strength (diagnostic odds ratio 16.3 vs. 6.4, respectively). Furthermore, a multivariable logistic regression showed that C1q+ DSA was a risk factor for AMR (OR = 16.80, P = 0.001), while high MFI DSAs were not. Graft survival was lower in high MFI C1q+ DSA in comparison with patients with C1q- high or low MFI DSA (at 6 years, 38%, 83% and 80%, respectively; P = 0.001). Both DSA strength and C1q-binding ability assessment seem valuable for improving pretransplant risk assessment. Since DSA C1q-binding ability was a better predictor of AMR and correlated with graft survival, C1q-SAB may be a particularly useful tool., (© 2016 Steunstichting ESOT.)

Desensitization with intravenous immunoglobulin (IVIG) and rituximab can improve transplantation rates in broadly sensitized kidney transplant recipients. However, long-term outcomes are lacking. Here we analyze long-term outcomes in living donor kidney transplant recipients desensitized with this regimen and compare them to low-risk recipients. Living donor kidney transplants that took place between July 2006 and December 2010 were considered retrospectively. The primary end point of the study was death-censored allograft survival at last follow-up. Secondary end points included patient survival, incidence of rejection, glomerular filtration rate (GFR), and proteinuria. There were 66 sensitized and 111 low-risk patients included. Average follow-up was 68 months. There was no difference in long-term patient or graft survival. The rate of rejection was similar in the groups with more early rejection in the sensitized group and more late rejection in the low-risk group. There was more antibody-mediated rejection in the sensitized group. Estimated GFR was similar during the follow-up period. Risk factors for rejection included a positive cross-match (HR: 2.4 CI: 1.35-4.40) and age (HR: 0.97 CI: 0.95-0.99). Desensitization with IVIG and rituximab has good long-term results with graft outcomes similar to non-HLA-sensitized patients despite higher immunologic risk., (© 2016 Steunstichting ESOT.)

Natural killer (NK) cells have been implicated in graft dysfunction. Here, we formulated hypothesis that distinct patterns of expression NK cells markers correlated with acute rejection in kidney transplantation. Therefore, we studied the pattern of NK cell markers CD56, CD57, and CD16 in different compartments of biopsies obtained from recipients diagnosed with acute graft rejection, with or without donor-specific antibodies (DSA). DSA-negative biopsies-from patients with acute T-cell mediated rejection (aTCMR) had an increased expression of CD56+ and CD57+ cells (P = 0.004 and P = 0.001) in the interstitial compartment in comparison with DSA-positive biopsies from patients acute antibody-mediated rejection (aABMR) with (aABMR C4d+) and without C4d deposition (aABMR C4d-). CD16+ cells was increased (P = 0.03) in the glomerular compartment in DSA-positive biopsies. We assume that CD16+ expression and antibody-dependent cellular cytotoxicity (ADCC) in microvascular injury can be associated with aABMR. IFN-γ release from cytoplasmic granules of NK cell could be associated with aTCMR. Our findings suggest that NK cells need to be carefully evaluated because variations in NK cell marker expression might imply the involvement of different immune system pathways in graft rejection., (© 2015 Steunstichting ESOT.)

The incidence and consequences of de novo donor-specific anti-HLA antibodies (DSAs) after liver transplantation (LT) are not well known. We investigated the incidence, risk factors, and complications associated with de novo DSAs in this setting. A total of 152 de novo liver-transplant patients, without preformed anti-HLA DSAs, were tested for anti-HLA antibodies, with single-antigen bead technology, before, at transplantation, at 1, 3, 6 and 12 months after transplantation, and thereafter annually and at each time they presented with increased liver-enzyme levels until the last follow-up, that is, 34 (1.5-77) months. Twenty-one patients (14%) developed de novo DSAs. Of these, five patients had C1q-binding DSAs (24%). Younger age, low exposure to calcineurin inhibitors, and noncompliance were predictive factors for de novo DSA formation. Nine of the 21 patients (43%) with de novo DSAs experienced an acute antibody-mediated rejection (AMR). Positive C4d staining was more frequently observed in liver biopsies of patients with AMR (9/9 vs. 1/12, P < 0.0001). Eight patients received a B-cell targeting therapy, and one patient received polyclonal antibodies. Only one patient required retransplantation. Patient- and graft-survival rates did not differ between patients with and without DSAs. In conclusion, liver-transplant patients with liver abnormalities should be screened for DSAs and AMR., (© 2015 Steunstichting ESOT.)

Graft survival seems to be worse in positive cross-match (HLAi) than in ABO-incompatible (ABOi) transplantation. However, it is not entirely clear why these differences exist. Sixty-nine ABOi, 27 HLAi and 10 combined ABOi+HLAi patients were included in this retrospective study, to determine whether the frequency, severity and the outcome of active antibody-mediated rejection (AMR) were different. Five-year death-censored graft survival was better in ABOi than in HLAi and ABOi+HLAi patients (99%, 69% and 64%, respectively, P = 0.0002). Features of AMR were found in 38%, 95% and 100% of ABOi, HLAi and ABOi+HLAi patients that had a biopsy, respectively (P = 0.0001 and P = 0.001). After active AMR, a declining eGFR and graft loss were observed more frequently in HLAi and HLAi+ABOi than in ABOi patients. The poorer prognosis after AMR in HLAi and ABOi+HLAi transplantations was not explained by a higher severity of histological lesions or by a less aggressive treatment. In conclusion, ABOi transplantation offers better results than HLAi transplantation, partly because AMR occurs less frequently but also because outcome after AMR is distinctly better. HLAi and combined ABOi+HLAi transplantations appear to have the same outcome, suggesting there is no synergistic effect between anti-A/B and anti-HLA antibodies., (© 2015 Steunstichting ESOT.)

Annual influenza vaccination is recommended in solid organ transplant (SOT) recipients. However, concerns have been raised about the impact of vaccination on antigraft alloimmunity. We evaluated the humoral alloimmune responses to influenza vaccination in a cohort of SOT recipients between October 2008 and December 2011. Anti-HLA antibodies were measured before and 4-8 weeks after influenza vaccination using a solid-phase assay. Overall, 169 SOT recipients were included (kidney = 136, lung = 26, liver = 3, and combined = 4). Five (2.9%) of 169 patients developed de novo anti-HLA antibodies after vaccination, including one patient who developed donor-specific antibodies (DSA) 8 months after vaccination. In patients with pre-existing anti-HLA antibodies, median MFI was not significantly different before and after vaccination (P = 0.73 for class I and P = 0.20 for class II anti-HLA antibodies) and no development of de novo DSA was observed. Five episodes of rejection (2.9%) were observed within 12 months after vaccination, and only one patient had de novo anti-HLA antibodies. The incidence of development of anti-HLA antibodies after influenza vaccination in our cohort of SOT recipients was very low. Our findings indicate that influenza vaccination is safe and does not trigger humoral alloimmune responses in SOT recipients., (© 2014 Steunstichting ESOT.)

Whole-organ pancreas transplantation is typically carried out using a Y-graft derived from the donor iliac vessels. We describe a case in which a 31-year-old male underwent a simultaneous pancreas-kidney transplant, but in which vessels from a different donor were used for the arterial anastomosis of the pancreas graft. Although initially there was good function, 18 months post-transplant the patient was admitted with diabetic ketoacidosis secondary to pancreas graft failure. Radiological investigations revealed complete occlusion of the vascular Y-graft, and laboratory investigations demonstrated donor-specific human leucocyte antigen (HLA) antibodies directed against HLA mismatches of the vessel donor. This case highlights the risks of using allogeneic vascular material for surgical anastomoses., (© 2014 Steunstichting ESOT.)

Many factors influence the long-term outcome of kidney transplantation, which is defined very schematically by patient death or renal dysfunction leading to graft loss. The most important of these factors is most likely the quality of the transplant itself, with kidneys from living donors showing a positive impact, while kidneys from expanded criteria donors show deleterious impacts. Various clinicopathological scores exist to predict mid- to long-term outcomes and avoid the transplantation of kidneys displaying inferior results. The key factors related to the recipient include their age as well as disease recurrence, HLA matching, HLA immunization, ethnic background, time on dialysis, and cardiovascular comorbidities. Renal function, defined based on estimated GFR and/or proteinuria values, is a result of all these factors. Delayed graft function has a detrimental long-term impact, as does the level of renal function impairment either in stable condition or in case of progressing dysfunction. Finally, although current immunosuppression regimes are highly efficient in preventing acute rejection, the burden of specific (diabetes, nephrotoxicity) and nonspecific (infection and cancer) side effects has significant negative long-term consequences that may well be worse in the future because of the increasing ages of both donors and recipients. The development of safer immunosuppression strategies is therefore crucial to improve long-term outcomes., (© 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

De novo donor-specific HLA antibodies (DSA) after renal transplantation are known to be correlated with poor graft outcome and the development of acute and chronic rejection. Currently, data for the influence of de novo DSA in patient cohorts including only living-donor renal transplantations (LDRT) are limited. A consecutive cohort of 88 LDRT was tested for the occurrence of de novo DSA by utilizing the highly sensitive Luminex solid-phase assay for antibody detection. Data were analyzed for risk factors for de novo DSA development and correlated with acute rejection (AR) and graft function. Patients with de novo DSA [31 (35%)] showed a trend for inferior graft function [mean creatinine change (mg/dL/year) after the first year: 0.15 DSA (+) vs. 0.02 DSA (-) (P = 0.10)] and a higher rate of AR episodes, especially in case of de novo DSA of both class I and II [6 (55%), (P = 0.05)]. Antibody-mediated rejection (AMR) appeared in five patients and was significantly correlated with de novo DSA (P = 0.05). Monitoring for de novo DSA after LDRT may help to identify patients at risk of declining renal function. Especially patients with simultaneous presence of de novo DSA class I and class II are at a high risk to suffer AR episodes., (© 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)