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Introduction: Immunoadsorption (IA) of isohemagglutinins is an often-crucial procedure in preparation of major ABO blood group-incompatible living donor kidney transplantation (ABOi LDKT). Standard citrate-based anticoagulation during the procedure has potential disadvantages for distinct patient groups. In this study, we report our experience with an alternative anticoagulation scheme using heparin during IA for selected patients. Methods: We conducted a retrospective analysis of all patients who underwent IA with heparin anticoagulation between February 2013 and December 2019 at our institution with focus on the safety and efficacy of the adapted procedure. For further validation, we compared graft function, graft survival, and overall survival with those of all recipients of living donor kidney transplants with or without pretransplant desensitizing apheresis for ABO antibodies at our institution during the same period. Results: In thirteen consecutive patients prepared for ABOi LDKT with IA with heparin anticoagulation, no major bleeding or other significant complications were observed. All patients achieved sufficient isohemagglutinin titer reduction to proceed to transplant surgery. Graft function, graft survival, and overall survival did not significantly differ from patients treated with standard anticoagulation for IA or ABO compatible recipients of living donor kidneys. Conclusion: IA with heparin in preparation of ABOi LDKT is safe and feasible for selected patients after internal validation.

Supplementary Methods and Data

Purpose:PD-(L)1–blocking antibodies have clinical activity in metastatic non–small cell lung cancer (NSCLC) and mediate durable tumor remissions. However, the majority of patients are resistant to PD-(L)1 blockade. Understanding mechanisms of primary resistance may allow prediction of clinical response and identification of new targetable pathways.Experimental Design:Peripheral blood mononuclear cells were collected from 35 patients with NSCLC receiving nivolumab monotherapy. Cellular changes, cytokine levels, gene expression, and polymorphisms were compared between responders and nonresponders to treatment. Findings were confirmed in additional cohorts of patients with NSCLC receiving immune checkpoint blockade.Results:We identified a genetic variant of a killer cell immunoglobulin-like receptor (KIR) KIR3DS1 that is associated with primary resistance to PD-1 blockade in patients with NSCLC. This association could be confirmed in independent cohorts of patients with NSCLC. In a multivariate analysis of the pooled cohort of 135 patients, the progression-free survival was significantly associated with presence of the KIR3DS1 allele (HR, 1.72; 95% confidence interval, 1.10–2.68; P = 0.017). No relationship was seen in cohorts of patients with NSCLC who did not receive immunotherapy. Cellular assays from patients before and during PD-1 blockade showed that resistance may be due to NK-cell dysfunction.Conclusions:We identified an association of the KIR3DS1 allelic variant with response to PD-1–targeted immunotherapy in patients with NSCLC. This finding links NK cells with response to PD-1 therapy. Although the findings are interesting, a larger analysis in a randomized trial will be needed to confirm KIRs as predictive markers for response to PD-1–targeted immunotherapy.

CXCL10 is a promising early noninvasive diagnostic marker for allograft rejection and predictive for long-term outcomes. However, its value when measured later in the posttransplant course has not yet been accurately analyzed.We investigated urinary CXCL10 in 141 patients from a prospective, observational renal transplant cohort with 182 clinically indicated allograft biopsies performed12 months posttransplant and corresponding urines. Urinary CXCL10 was retrospectively quantified on stored urines using the MSD V-Plex Chemokine Panel 1 sandwich immunoassay (Meso Scale Discovery). The primary outcome was a composite of allograft loss/renal function decline (30% estimated glomerular filtration rate [eGFR]-decrease between index biopsy and last follow-up).Seventy-two patients (51%) reached the primary outcome, and their urinary CXCL10 levels were significantly higher at the time of their biopsy compared with patients with stable allograft function (median 9.3 ng/mmol vs 3.3 ng/mmol, P.0001). Time-to-endpoint analyses according to high/low urinary CXCL10 demonstrated that low urinary CXCL10 (≤7.0 ng/mmol) was associated with 73% 5-year event-free graft survival compared with 48% with high urinary CXCL10 (7.0 ng/mmol; P = .0001). Even in histologically quiescent patients, high urinary CXCL10 was associated with inferior endpoint-free graft survival (P = .003), and it was an independent predictor of the primary outcome (P = .03).This study demonstrates that urinary CXCL10 has a promising diagnostic performance for detection of late allograft rejection and is an independent predictor of long-term renal allograft outcomes, even in histologically quiescent patients.

In this study, we investigated the clinical impact of different urinary tract infection (UTI) phenotypes occurring within the first year after renal transplantation. The population included 2368 transplantations having 2363 UTI events. Patients were categorized into four groups based on their compiled UTI events observed within the first year after transplantation: (i) no colonization or UTI (n = 1404; 59%), (ii) colonization only (n = 353; 15%), (iii) occasional UTI with 1-2 episodes (n = 456; 19%), and (iv) recurrent UTI with ≥3 episodes (n = 155; 7%). One-year mortality and graft loss rate were not different among the four groups, but patients with recurrent UTI had a 7-10 ml/min lower eGFR at year one (44 ml/min vs. 54, 53, and 51 ml/min; p .001). UTI phenotypes had no impact on long-term patient survival (p = .33). However, patients with recurrent UTI demonstrated a 10% lower long-term death-censored allograft survival (p .001). Furthermore, recurrent UTI was a strong and independent risk factor for reduced death-censored allograft survival in a multivariable analysis (HR 4.41, 95% CI 2.53-7.68, p .001). We conclude that colonization and occasional UTI have no impact on pertinent outcomes, but recurrent UTI are associated with lower one-year eGFR and lower long-term death-censored allograft survival. Better strategies to prevent and treat recurrent UTI are needed.

Eplets are defined as distinct amino acid configurations on the surface of HLA molecules. The aim of this study was to estimate the immunogenicity of HLA-DQ eplets in a cohort of 221 pregnancies with HLA-DQ mismatches. We defined the immunogenicity of an eplet by the frequency of antibody responses against it. Around 90% of all listed DQB1 or DQA1 eplets were at least five times mismatched and thus included for the calculation of their immunogenicity. The DQB1 eplets with the five highest immunogenicity scores were 55PP, 52PR, 52PQ, 85VG and 45EV; 25% of all DQB1 eplets were not reacting. The DQA1 eplets with the five highest immunogenicity scores were 25YS, 47QL, 55RR, 187T and 18S; 17% of all DQA1 eplets were not reacting. The immunogenicity score had a slightly higher area under the curve to predict development of child-specific antibodies than various molecular mismatch scores (eg, eplet mismatch load, amino acid mismatch load). Overlapping eplets were identified as a barrier to unambiguously assign the immunogenicity score based on HLA antibody reaction patterns. In this conceptual study, we explored the immunogenicity of HLA-DQ eplets and created a map of potentially immunogenic regions on HLA-DQ molecules, which requires validation in clinical transplant cohorts.

Eplets are functional units of structural epitopes on donor HLA, potentially recognized by complementarity-determining regions of the paratope of the recipients' B-cell receptors or antibodies (Ab). Their individual immunogenicity is poorly described, yet this feature would be of clinical importance for pretransplant risk assessment. The aim of this study was to determine the relative immunogenicity of HLA class I eplets in the pregnancy setting, where mismatched eplets are present on paternal HLA antigens of the unborn child. One hundred fifty-nine predominantly Caucasian mothers giving birth at the University Hospital Basel and their first newborns were HLA-typed at high-resolution by next-generation sequencing (NGS) (NGSgo Workflow and NGSengine from GenDx; sequencing with a Miseq from Illumina) and eplets were determined using HLAMatchmaker. HLA class I specific IgG Ab was assessed in maternal sera drawn immediately after full-term delivery, by OneLambda LABScreen single antigen ibeads. The Ab profile was subsequently evaluated for eplet-associated patterns. All 72 currently Ab-verified HLA class I eplets were examined for their immunogenicity according to the frequency of child-specific HLA Ab (CSA) directed against their structures. Four hundred twelve of 477 (86.4%) paternal HLA-A, -B or -C alleles were mismatched. CSA were present in 46 mothers (28.9%), directed against 80 (19.4%) of these mismatches. The 10 most immunogenic eplets were 62GK, 145KHA, 144TKH, 62GE, 107W, 80I, 82LR, 41T, 127K, 45KE with immunogenicity rates between 45.8% and 27.3%. This pregnancy study also identified five non-reactive eplets: 62RR, 76ESN, 80TLR, 156DA, 163RW. Based on our results, immunogenic hot and cold spots on the surface of HLA class I molecules were localized and visualized on 3D models. This study strengthens the presumption that different eplets represent different immunogenic potentials. Validation of these results in the clinical transplant setting is an essential next step in identifying those eplets representing a particularly high-risk potential.

The activation of bipolar conduction was investigated for two 4H-SiC 10 kV JBS-diodes which differ in the area ratio between p-doped and n-doped regions (Ws/WPin). Quasi-static measurements at low electric current densities (j < 2.5 Acm-2) were performed in a temperature range between 25°C and 500°C. The lower ratio (Ws/WPin) leads to a higher threshold voltage. On the other hand lower electric power density is neccessary to trigger temperature enhanced bipolar activation. Moreover, the lower ratio improves the leakage currents in blocking direction. Dynamic surge current investigations were performed in a temperature range between 25°C and 250°C. The turning voltages, which indicate the transition from unipolar to bipolar conduction, are lower for the diode with smaller ratio (Ws/WPin) but the self-heating of the device is more severe in comparison to the other diode with the larger ratio. Both devices are stable under extreme conditions (high temperatures/ surge current) and exhibit special benefits for different applications.

BackgroundPatients returning to dialysis after graft loss have high early morbidity and mortality.MethodsWe used data from the Swiss Transplant Cohort Study to describe the current practice and outcomes in Switzerland. All patients who received a renal allograft between May 2008 and December 2014 were included. The patients with graft loss were divided into two groups depending on whether the graft loss occurred within 1 year after transplantation (early graft loss group) or later (late graft loss group). Patients with primary non-function who never gained graft function were excluded.ResultsSeventy-seven out of 1502 patients lost their graft during follow-up, 40 within 1 year after transplantation. Eleven patients died within 30 days after allograft loss. Patient survival was 86, 81 and 74% at 30, 90 and 365 days after graft loss, respectively. About 92% started haemodialysis, 62% with definitive vascular access, which was associated with decreased mortality (hazard ratio = 0.28). At the time of graft loss, most patients were on triple immunosuppressive therapy with significant reduction after nephrectomy. One year after graft loss, 77.5% (31 of 40) of patients in the early and 43.2% (16 out of 37) in the late-loss group had undergone nephrectomy. Three years after graft loss, 36% of the patients with early and 12% with late graft loss received another allograft.ConclusionIn summary, our data illustrate high mortality, and a high number of allograft nephrectomies and re-transplantations. Patients commencing haemodialysis with a catheter had significantly higher mortality than patients with definitive access. The role of immunosuppression reduction and allograft nephrectomy as interdependent factors for mortality and re-transplantation needs further evaluation.

Background Cytomegalovirus (CMV) serostatus and CMV replication are considered as risk factors for inferior graft and patient survival after renal transplantation, but long-term outcome data are limited. The aim of this retrospective single-centre study was to investigate the impact of CMV serostatus and CMV replication/disease on long-term outcomes in a well-defined cohort managed by a standardized CMV prevention/treatment protocol. Methods We investigated 599 consecutive kidney transplantations having a CMV prevention protocol consisting of either prophylaxis (D+/R− and R+ with ATG induction) or screening/deferred therapy (R+ without ATG induction). Patients were grouped according to CMV serostatus [high risk (D+/R−): n = 122; intermediate risk (R+): n = 306; low risk (D−/R−): n = 171] and occurrence of CMV replication/disease (no CMV replication: n = 419; asymptomatic CMV replication: n = 110; CMV syndrome: n = 39; tissue-invasive CMV disease: n = 31). The median follow-up time was 6.5 years. Results Graft and patient survival were not different among the three CMV serostatus groups as well as the four CMV replication/disease groups (P ≥ 0.44). Eighty-seven patients died, 17 due to infections (21%), but none was attributable to CMV. The overall hospitalization incidence for CMV-related infection was 3% (17/599 patients). The incidence of clinical and (sub)clinical rejection was similar among the groups (P ≥ 0.17). In a multivariate Cox proportional hazard model, neither CMV serostatus, nor CMV replication, nor CMV disease were independent predictors for patient death or graft failure, respectively. Conclusions This retrospective single-centre study suggests that the negative impact of CMV infection on long-term patient and allograft survival as well as on allograft rejection can be largely eliminated with current diagnostic/therapeutic management.

BackgroundPre-transplant donor specific antibodies (DSA), directed at non-self human leukocyte antigen (HLA) protein variants present in the donor organ, have been associated with worse outcomes in kidney transplantation. The impact of the mean fluorescence intensity (MFI) and the target HLA antigen of the detected DSA has, however, not been conclusively studied in a large cohort with a complete virtual cross-match (vXM).MethodsWe investigated the effect of pre-transplant DSA on the risk of antibody-mediated rejection (ABMR), graft loss, and the rate of eGFR decline in 411 DSA positive transplants and 1804 DSA negative controls.ResultsPre-transplant DSA were associated with a significantly increased risk of ABMR, graft loss, and accelerated eGFR decline. DSA directed at Class I and Class II HLA antigens were strongly associated with increased risk of ABMR, but only DSA directed at Class II associated with graft loss. DSA MFI markedly affected outcome, and Class II DSA were associated with ABMR already at 500-1000 MFI, whereas Class I DSA did not affect outcome at similar low MFI values. Furthermore, isolated DSA against HLA-DP carried comparable risks for ABMR, accelerated eGFR decline, and graft loss as DSA against HLA-DR.ConclusionOur results have important implications for the construction and optimization of vXM algorithms used within organ allocation systems. Our data suggest that both the HLA antigen target of the detected DSA as well as the cumulative MFI should be considered and that different MFI cut-offs could be considered for Class I and Class II directed DSA.

Proteinuria is frequent in patients with nephropathies and associated with progressive kidney disease and risk for end stage kidney disease. However, the relevance of deceased donor proteinuria on transplant outcome remains uncertain. In this nationwide cohort study, we evaluated the prevalence of proteinuria in deceased donor candidates and measured the impact on outcome after kidney transplantation.Data from the Swiss Organ Allocation System and the Swiss Transplant Cohort Study were analyzed, comprising 1725 donors and 1516 recipients transplanted between 2008 and 2019. We correlated urine findings with donor characteristics and quantified the impact of proteinuria on allograft function at 12 months and survival.Proteinuria influenced allocation decisions in 4.5% of nonimmunological organ declines and was the leading cause for decline in 0.2% of cases. 74.1%, 51.4%, and 35.3% of donor candidates had a baseline proteinuria above 15, 30, and 50 mg protein/mmol urine creatinine, respectively. Proteinuria above 30 mg/mmol was associated with female donor sex, mechanical resuscitation, acute kidney injury, and time delay between ICU entry and urine sampling. Donor proteinuria was not associated with patient or allograft survival, nor allograft function at 12 months.We report a high prevalence of proteinuria in donor candidates, without evidence of a deleterious impact of proteinuria on graft function and/or survival. Therefore, low-level proteinuria should not be considered a limiting contraindication for kidney allocation in deceased donor transplant.

The aim of this retrospective single-center study was to investigate the short- and long-term impact of neutropenia occurring within the first year after kidney transplantation, with a special emphasis on different neutropenia grades. In this unselected cohort, 225/721 patients (31%) developed 357 neutropenic episodes within the first year post-transplant. Based on the nadir neutrophil count, patients were grouped as neutropenia grade 2 (

MELD exceptions are designed to equipoise liver transplant waiting list survival. We aimed to analyze the impact of the MELD Upgrade rule and all other MELD exceptions on the liver transplant waiting list outcomes during 2012-2017 in Switzerland.We conducted a nationwide cohort study including all adult patients registered on the Swiss liver transplant waiting list between 2012 and 2017. Waiting list mortality and access to transplantation were analyzed, considering MELD exceptions as time-dependent covariates.730 patients were included. Patients with MELD Upgrade exceptions had a higher risk of dying while on the waiting list (OR 2.13; CI 95% 1.30-3.47) and also an increased likelihood of receiving a liver transplantation, when compared to patients without MELD exceptions. Patients with any type of MELD exceptions were more likely to be transplanted when compared to patients without MELD exceptions. The proportion of patients with MELD exceptions increased from 2012 to 2017 (44% vs 88%). Allocation MELD at the time of transplantation showed an annual increase (23 ± 8 points vs 32 ± 5 points, p 0.001).Only patients with MELD Upgrade exceptions had the expected combination of higher waiting list mortality and quicker access to liver transplantation.

Background: Data on individualized immunosuppressive protocols for the pediatric heart recipients are missing in Europe. To contribute to this very small but specialized field, we describe the use of induction therapy (IT) in pediatric heart transplant patients in Switzerland and the retrospective outcomes. Method: This is a retrospective national database analysis of children

Previous studies have indicated an association between coronavirus disease 2019 (COVID-19) and acute kidney injury (AKI) but lacked a control group. The prospective observational COronaVIrus-surviVAl (COVIVA) study performed at the University Hospital, Basel, Switzerland consecutively enrolled patients with symptoms suggestive of COVID-19. We compared patients who tested positive for SARS-CoV-2 with patients who tested negative but with an adjudicated diagnosis of a respiratory tract infection, including pneumonia. The primary outcome measure was death at 30 days, and the secondary outcomes were AKI incidence and a composite endpoint of death, intensive care treatment or rehospitalization at 30 days. Five hundred and seven patients were diagnosed with respiratory tract infections, and of those, 183 (36%) had a positive PCR swab test for SARS-CoV-2. The incidence of AKI was higher in patients with COVID-19 (30% versus 12%, p &lt, 0.001), more severe (KDIGO stage 3, 22% versus 13%, p = 0.009) and more often required renal replacement therapy (4.4% versus 0.93%, p = 0.03). The risk of 30-day mortality and a composite endpoint was higher in patients with COVID-19-associated AKI (adjusted hazard ratio (aHR) mortality 3.98, 95% confidence interval (CI) 1.10–14.46, p = 0.036, composite endpoint aHR 1.84, 95% CI 1.02–3.31, p = 0.042). The mortality risk was attenuated when adjusting for disease severity (aHR 3.60, 95% CI 0.93–13.96, p = 0.062). AKI occurs more frequently and with a higher severity in patients with COVID-19 and is associated with worse outcomes.

Background and Aims Previous studies have indicated a coherency between coronavirus disease 2019 (COVID-19) and acute kidney injury (AKI), indicating poor outcomes. However, most studies only included patients with COVID-19 and lacked a control group. Therefore, the aim of this study was to investigate the prevalence and prognostic impact of AKI in patients with COVID-19 in comparison with other respiratory tract infections. Method The prospective single-center observational case-control COronaVIrus surviVAl (COVIVA, clinicaltrials.gov NCT04366765) study performed at the University Hospital Basel Switzerland consecutively enrolled patients presenting to the emergency department with symptoms suggestive of COVID-19 between March 23 and May 31, 2020. The final diagnosis that led to the inclusion in the study was adjudicated by physicians after reviewing all available medical data including laboratory test results 30 days after discharge. For this analysis, we compared patients tested positive for SARS-CoV-2 with patients tested negative but with an adjudicated diagnosis of upper or lower respiratory tract infection including pneumonia. Primary outcome measure was death at 30 days, secondary outcomes were AKI incidence, renal recovery and need for renal replacement therapy. AKI was defined according to the serum creatinine criteria of the 2012 KDIGO clinical practice guideline. Results Of the 1086 patients included, 507 had a final adjudicated diagnosis of respiratory tract infection and were eligible for this analysis. Of those, 183 (36%) had a positive PCR swab test for SARS-CoV-2. Baseline characteristics were comparable between patients with and without COVID-19. AKI occurred in 95 patients (19%) with a higher incidence (30%, 95%CI 24-37 versus 12%, 95%CI 9-17, p Conclusion AKI occurs more frequently and more severely in patients with COVID-19 compared to other respiratory tract infections. It is associated with an increased risk for death, with the highest risk observed in COVID-19 patients. This underlines the augmented burden of AKI during the COVID-19 pandemic.

Introduction: To date, 23 lung transplant recipients have been described with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections worldwide Eight had severe coronavirus disease 2019 (COVID-19), but none were placed on extracorporeal membrane oxygenation (ECMO) support We aimed to describe our experience Methods: Lung transplant recipients who were admitted to our hospital with SARS-CoV-2 infections from the beginning of the pandemia until May 25th, 2020 were included Clinical charts were retrospectively retrieved and data analysed Results: Four patients (3 males, 75%) with a median age of 58 5 years (47-66) were admitted for SARS-CoV-2 infections in our center Three patients had double-lung transplantation for chronic thromboembolic pulmonary hypertension, idiopathic pulmonary fibrosis and cystic fibrosis One patient had singlelung transplantation for non-specific interstitial pneumonia SARS-CoV-2 infections were diagnosed by nasopharyngeal swabs in all patients within one month post-transplant (n=2), or after 13 months (n=1) and 15 years (n=1) Dyspnea was present in all patients Worsening of symptoms occurred in three patients after a median of 8 days (1 to 8) after diagnosis Imaging showed a highly variable degree of infiltrations Mechanical ventilation was required in three patients They all underwent prone positioning Veno-venous ECMO was required in two patients In all patients, immunosuppression consisted of prednisone and tacrolimus, while mycophenolate mofetil was stopped Treatment with hydroxychloroquine was attempted in the first three patients At last follow-up, one patient was discharged home and one was weaned from mechanical ventilation Both ECMO supported patients died from multiple organ failure, despite ECMO could be weaned in one patient Conclusion: A highly variable course of COVID-19 disease was observed in four patients after lung transplantation More data is needed to better understand prognostic factors and management of this patient cohort

Purpose: PD-(L)1–blocking antibodies have clinical activity in metastatic non–small cell lung cancer (NSCLC) and mediate durable tumor remissions. However, the majority of patients are resistant to PD-(L)1 blockade. Understanding mechanisms of primary resistance may allow prediction of clinical response and identification of new targetable pathways. Experimental Design: Peripheral blood mononuclear cells were collected from 35 patients with NSCLC receiving nivolumab monotherapy. Cellular changes, cytokine levels, gene expression, and polymorphisms were compared between responders and nonresponders to treatment. Findings were confirmed in additional cohorts of patients with NSCLC receiving immune checkpoint blockade. Results: We identified a genetic variant of a killer cell immunoglobulin-like receptor (KIR) KIR3DS1 that is associated with primary resistance to PD-1 blockade in patients with NSCLC. This association could be confirmed in independent cohorts of patients with NSCLC. In a multivariate analysis of the pooled cohort of 135 patients, the progression-free survival was significantly associated with presence of the KIR3DS1 allele (HR, 1.72; 95% confidence interval, 1.10–2.68; P = 0.017). No relationship was seen in cohorts of patients with NSCLC who did not receive immunotherapy. Cellular assays from patients before and during PD-1 blockade showed that resistance may be due to NK-cell dysfunction. Conclusions: We identified an association of the KIR3DS1 allelic variant with response to PD-1–targeted immunotherapy in patients with NSCLC. This finding links NK cells with response to PD-1 therapy. Although the findings are interesting, a larger analysis in a randomized trial will be needed to confirm KIRs as predictive markers for response to PD-1–targeted immunotherapy.

Kidney transplantation from older and marginal donors is effective to confront organ shortage. However, limitations after transplantation of kidneys from very marginal kidney donors remain unclear. We compared patient and graft outcome, achieved allograft function and quality of life of renal transplantations from Very Senior Donors (VSD, defined as donors aged 70 years and older) with Senior Donors (SD, aged 60-70 years) and Regular Donors (RD, aged younger than 60 years) in Switzerland. We evaluated the outcome of 1554 adult recipients of deceased donor kidney transplantations from 05/2008 to 12/2019; median follow-up was 4.7 years. Failure-free survival (freedom from graft loss or death), glomerular filtration rate (eGFR), and quality of life at 12 months were analyzed for RD (reference group, n = 940), SD (n = 404), and VSD (n = 210). Failure-free survival decreased with increasing donor age, mainly attributable to premature graft loss. Still, overall 5-year failure-free survival reached 83.1%, 81.0%, and 64.0% in the RD, SD, and VSD subgroups, respectively. eGFR 12 months post-transplantation was significantly higher in RD compared with SD and VSD. The acceptance rate of donor candidates for kidney TPL was 78% for the entire cohort (87% for RD, 79% for SD, and 56% for VSD). Deceased donor kidney transplantation from donors aged 70 years or older is associated with an inferior, yet acceptable failure-free outcome, with sustained quality of life.

Screening for de novo donor-specific HLA antibodies (DSA) after kidney transplantation is widely recommended. The aim of this single-center, cross-sectional study was to investigate the frequency of therapeutic interventions triggered by de novo DSA screening. We included 464 patients screened for de novo DSA at annual visits after a median of 5 years post-transplant (range 1 to 19 years). Overall, de novo DSA were detected in 55/464 patients (11.9%) with a stepwise increase of the prevalence from 4.9% at one-year post-transplant to 18.9% at >10 years post-transplant. Subsequent allograft biopsies were performed in 24/55 patients (44%). The main reasons to omit biopsies were good/stable allograft function and anticipated lack of clinical consequences (e.g. relevant comorbidities). Rejection processes were detected in 16/24 biopsies (67%). Therapeutic interventions were made in 18/464 screened patients (3.9%) with a significantly higher rate in the youngest quartile of patients (≤48 years; 7.9%) compared to the middle 50% (49-67 years; 3%) and the oldest quartile (≥68 years; 1.7%) (p=0.03). Our study suggests that the frequency of therapeutic interventions triggered by de novo DSA screening after kidney transplantation is overall low, but significantly higher in younger patients, arguing for a personalized, age-adapted de novo DSA screening strategy.

Background and objectives Antibodies (Ab) against HLA and HPA antigens play an important role in HCT. In this prospective study we evaluated prevalence and kinetics of HLA- and HPA-Ab after HCT, including a possible donor-recipient transfer and their clinical relevance in respect to platelet transfusion refractoriness (PTR). Materials and methods Patients were consecutively recruited. Ab were determined by microbead assay technique and a mean fluorescence intensity cut-off of 1,000. Results At baseline, 21 donors (42 %) and 27 patients (54 %) had HLA-Ab with a mean panel reactivity (cPRA) of 34.9 ± 29.4 % and 46.1 ± 36.5 %, respectively. We observed a significant higher number of HLA-Ab specificities in female donors and patients and a predominance of HLA-class I Ab. At day 0 we detected an increase of HLA-Ab (from 526 to 673) and cPRA (55.2 ± 31.9 %). Thirty-six patients (72 %) developed new HLA-Ab, mainly 3 weeks after HCT. In 7 patients an HLA-Ab with the same specificity as detected in the corresponding donor emerged, suggesting a possible transfer from the donor to the recipient. Overall, MFI showed a high variation. Type and number of transfusions were not associated with number and intensity of HLA-Ab (ρ: -0.05 – 0.02). Number of HLA-Ab, cPRA and intensity were not associated with PTR, which occurred in 9 patients (18 %) and none had bleeding WHO > 2. Conclusions Although a considerable number of patients have and develop HLA-Ab before and early after HCT, we found no association with PTR and bleeding and management should be individualized.

We report the effectiveness of daratumumab, a human IgGκ monoclonal antibody targeting CD38 on plasma cells, for therapy-refractory antibody-mediated rejection (AMR) due to blood group antibodies in a 59-year-old man who received a living ABO-incompatible kidney transplantation. Standard treatment options for AMR due to blood group antibodies including immunoadsorption, lymphocyte depletion with anti-human T-lymphocyte globulins, intravenous methylprednisolone pulses and eculizumab limited tissue injury, however failed to sufficiently suppress blood group antibody production. After administration of daratumumab as a rescue therapy, blood group antibody titers decreased and remained at low levels without further immunoadsorption and allowed kidney graft function to recover.

The iron(IV) oxido complex [(tmc)Fe=O(OTf)]OTf with the macrocyclic ligand 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclo-tetradecane (tmc) has been synthesized using ozone as an oxidant. By adding water to this compound the complex [(H2 O)(tmc)Fe=O)](OTf)2 could be prepared. This complex is important in regard to a better understanding of the reactivity of FeIV oxido complexes. Mossbauer measurements using the solid compound showed an isomer shift of δ=0.19 mm s-1 and a quadrupole splitting ΔEQ =1.38 mm s-1 , confirming the high-valent FeIV state. DFT calculations were performed and led to an assignment of triplet spin multiplicity. Crystallographic characterization of [(H2 O)(tmc)Fe=O)](OTf)2 as well as of starting materials [(tmc)Fe(CH3 CN)](OTf)2 and [(tmc)Fe(OTf)]OTf together with previous results strongly suggest that [(H2 O)(tmc)Fe=O)](OTf)2 was formed similar to the oxido-hydroxido tautomerism analogous to heme systems.

We reported previously on the widespread occurrence of anti-HLA alloantibodies of the IgA isotype (anti-HLA IgA) in the sera of solid-organ re-transplantation (re-tx) candidates (Arnold et al., ). Specifically focussing on kidney re-tx patients, we now extended our earlier findings by examining the impact of the presence and donor specificity of anti-HLA IgA on graft survival. We observed frequent concurrence of anti-HLA IgA and anti-HLA IgG in 27% of our multicenter collective of 694 kidney re-tx patients. This subgroup displayed significantly reduced graft survival as evidenced by the median time to first dialysis after transplantation (TTD 77 months) compared to patients carrying either anti-HLA IgG or IgA (TTD 102 and 94 months, respectively). In addition, donor specificity of anti-HLA IgA had a significant negative impact on graft survival (TTD 74 months) in our study. Taken together, our data strongly indicate that presence of anti-HLA IgA, in particular in conjunction with anti-HLA-IgG, in sera of kidney re-tx patients is associated with negative transplantation outcome.