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Purpose: Diarrhea is an important cause of morbidity and mortality in immunocompromised patients. After including sapovirus to the viral gastroenteritis screening of our institution's laboratory, we noticed an increase in sapovirus infections among kidney transplant recipients. Therefore, we assumed former gastrointestinal tract infections with unidentified pathogens could have been caused by sapovirus. To better understand the characteristics of a sapovirus infection in a high-risk group we initiated this study., Methods: Over a period of 6 months, all transplant recipients with diarrhea and later identified viral/unknown pathogens were included. Kidney function, levels of immunosuppressants and  c-reactive protein, acid-base balance, onset of symptoms and time of hospitalization were analyzed., Results: Among 13 hospitalized kidney transplant recipients sapovirus was detected in four patients, while in the remaining nine, three were diagnosed with norovirus, one with cytomegalovirus, one with inflammatory bowel disease and in four patients no pathogen was identified. Even though statistically not significant, creatinine levels at admission tended to be higher in sapovirus patients (median: sapovirus: 3.3 mg/dl (1.3; 5.0), non-sapovirus: 2.5 mg/dl (1.1; 4.9), p = 0.710). Also, Tacrolimus levels showed the same trend (sapovirus: 13.6 ng/ml (12.9; 13.6), non-sapovirus: 7.1 ng/ml (2.6; 22.6), p = 0.279). On discharge creatinine levels improved equally in both groups (sapovirus: 1.7 mg/dl (1.4; 3.2), non-sapovirus: 2 mg/dl (1.0; 3.6), p = 0.825)., Conclusion: In high-risk patients, early symptomatic treatment remains crucial to protect the transplant`s function. In our cohort all patients recovered well. Larger cohorts and longer follow-up times are needed to detect the long-term consequences and a potential need for further research regarding specific treatment., Trial Registration: The study has been registered on DRKS (trialsearch.who.int), Reg. Nr. DRKS00033311 (December 28th 2023)., (© 2024. The Author(s).)

Background: Benralizumab reduces exacerbations and long-term oral glucocorticosteroid (OCS) exposure in patients with severe eosinophilic asthma. In patients with eosinophilic granulomatosis with polyangiitis (EGPA), uncontrolled symptoms and exacerbations of asthma and chronic rhinosinusitis (CRS) are important reasons for continued OCS therapies. We aimed to describe outcomes of patients with severe asthma and EGPA treated with benralizumab in real-life., Methods: We retrospectively analyzed adult patients from the Severe Asthma Unit at LMU Munich diagnosed with severe asthma and EGPA treated with benralizumab, differentiating two groups: Group A, patients with a stable daily OCS dose and diagnosis of EGPA >6 months ago; and Group B, patients treated with high-dose daily OCS due to recent diagnosis of EGPA <6 months ago. We compared outcome parameters at baseline and 12 months after initiation of benralizumab, including respiratory exacerbations, daily OCS dose, and lung function., Results: Group A included 17 patients, all receiving OCS therapy and additional immunosuppressants; 15 patients (88%) continued benralizumab for more than 12 months, demonstrating a significant reduction in daily OCS dose and exacerbations while FEV1 increased. Group B included 9 patients, all with high-dose daily OCS and some receiving cyclophosphamide pulse therapy for life-threatening disease. Benralizumab addition during induction was well tolerated. A total of 7/9 (78%) continued benralizumab for more than 12 months and preserved EGPA remission at the 12-month timepoint., Conclusion: In this real-life cohort of patients with severe asthma and EGPA, benralizumab initiation during remission maintenance reduced respiratory exacerbations and daily OCS dose. Benralizumab initiation during remission induction was associated with a high rate of clinical EGPA remission., Competing Interests: CM reports speaker and/or consultancy fees from Sanofi, outside of the submitted work. PM reports speaker and/or consultancy fees from AstraZeneca, ResMed, Insmed, Vertex, all outside of the submitted work. US has received consulting fees from Ablynx, Alexion, and Vifor Pharma and reports research support from Vifor Pharma, Ablynx/Sanofi, and Alexion, all outside the submitted work. UG received speaker honoraria from AstraZeneca outside of the submitted work. HSK served as consultant and advisor or review panel member for AbbVie, Amgen, AstraZeneca, Biogen, BMS, Celgene, Gilead, Galapagos, Hexal Sandoz, Janssen-Cilag, Elli Lilly, Medac, MSD, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, and UCB, all outside the submitted work. JB reports speaker and/or consultancy fees from AstraZeneca, GSK, Novartis, Sanofi, all outside of the submitted work. NK reports speaker and/or consultancy fees from AstraZeneca and GSK, all outside of the submitted work. KM reports speaker and/or consultancy fees from AstraZeneca, Chiesi, GSK, Novartis, Sanofi, all outside of the submitted work. The author report no other conflicts of interest in this work., (© 2024 Mümmler et al.)

The diagnosis of systemic vasculitis (SV) is a major clinical challenge due to the very different forms of presentation and requires an interdisciplinary approach. Targeted laboratory diagnostics support making the diagnosis, differential diagnosis and classification and are also a key component in the detection of active organ manifestations and treatment complications. The basic laboratory tests include the erythrocyte sedimentation rate (ESR), C‑reactive protein (CRP), blood count, serum creatinine, urinalysis, specific autoantibodies, complement, immunoglobulins, cryoglobulins and hepatitis B and C serology. Antineutrophil cytoplasmic autoantibodies (ANCA), antiglomerular basement membrane antibodies (anti-GBM antibodies) and anti-C1q antibodies are valuable laboratory markers for the diagnosis of the various forms of small vessel vasculitis. There are no specific laboratory tests for the diagnosis of medium and large vessel vasculitis. Despite advances in our understanding of the pathogenesis of vasculitis, no biomarkers have yet been identified that can be reliably used to guide treatment or that are useful in distinguishing vasculitis from other inflammatory diseases such as infections or treatment complications., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objectives: Giant cell arteritis (GCA) is one of the most common forms of vasculitis. There is an abundance of studies which are conducted in a randomised controlled trial setting but limited with respect to cohort size and follow-up time. GeVas is the first large-scale registry for vasculitides in German-speaking countries that enables to evaluate this rare disease. Herein we focus on the subgroup of GCA patients including follow-up data up to one year., Methods: GeVas is a prospective, web-based, multicentre registry for the documentation of organ manifestations, outcomes, and therapy regimens in vasculitides. Recruitment started in June 2019. By April 2023, 15 centres were initiated and have started to enrol patients., Results: After 4 years, 195 GCA-patients were included in the registry, of which 64% were female and 36% were male. The average age was 76 years at the time of recruitment (IQR=69-82). Seventy-nine percent were included in the registry because of a newly diagnosed GCA and 21% because of a relapse. At the first assessment most of the patients (89%) described general symptoms. Thirty-one percent stated ocular symptoms. Cranial symptoms were documented in 78% of the cases. All patients were documented with immunosuppressive treatment at start, of whom 95% received prednisolone, 16% cyclophosphamide, 20% methotrexate, and 48% tocilizumab. After three months 62% and after one year 91% of the patients achieved remission., Conclusions: Regarding demographics, clinical manifestations and diagnostics, our study showed a similar composition compared to other studies. However, our data differed in terms of treatment regimens.

Objectives: Prospective long-term observational data on the disease course of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were missing in Germany to date. Therefore, the Joint Vasculitis Registry in German-speaking countries (GeVas) has been established to follow the course of patients with AAV. The aim of this study is to present baseline data of patients with newly diagnosed and relapsing AAV enrolled in the GeVas registry., Methods: GeVas is a prospective, web-based, multicentre, clinician-driven registry for the documentation of organ manifestations, damage, long-term outcomes, and therapy regimens in various types of vasculitis. Recruitment started in June 2019., Results: Between June 2019 and October 2022, 266 patients with AAV were included in the GeVas registry: 173 (65%) with new-onset and 93 (35%) with relapsing AAV. One hundred and sixty-two (61%) patients were classified as granulomatosis with polyangiitis (GPA), 66 (25%) as microscopic polyangiitis (MPA), 36 (13%) as eosinophilic granulomatosis with polyangiitis (EGPA), and 2 (1%) as renal limited AAV. The median age was 59 years (51-70 years, IQR), 130 (51%) patients were female. Most patients were ANCA positive (177; 67%) and affected by general symptoms, pulmonary, ear nose throat (ENT), renal and neurological involvement. For induction of remission, the majority of patients received glucocorticoids (247, 93%) in combination with either rituximab (118, 45%) or cyclophosphamide (112, 42%)., Conclusions: Demographic characteristics are comparable to those in other European countries. Differences were found regarding ANCA status, frequencies of organ manifestations, and therapeutic regimens. The GeVas registry will allow longitudinal observations and prospective outcome measures in AAV.

Introduction: In pregnancy-related atypical hemolytic uremic syndrome (p-aHUS), transferring recommendations for treatment decisions from nonpregnant cohorts with thrombotic microangiopathy (TMA) is difficult. Although potential causes of p-aHUS may be unrelated to inherent complement defects, peripartal complications such as postpartum hemorrhage (PPH) or (pre)eclampsia or Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome may be unrecognized drivers of complement activation., Methods: To evaluate diagnostic and therapeutic decisions in the practical real-life setting, we conducted an analysis of a cohort of 40 patients from 3 German academic hospitals with a diagnosis of p-aHUS, stratified by the presence ( n  = 25) or absence ( n  = 15) of PPH., Results: Histological signs of TMA were observed in 84.2% of all patients (100% vs. 72.7% in patients without or with PPH, respectively). Patients without PPH had a higher likelihood (20% vs. 0%) of pathogenic genetic abnormalities in the complement system although notably less than in other published cohorts. Four of 5 patients with observed renal cortical necrosis (RCN) after PPH received complement inhibition and experienced partially recovered kidney function. Patients on complement inhibition with or without PPH had an increased need for kidney replacement therapy (KRT) and plasma exchange (PEX). Because renal recovery was comparable among all patients treated with complement inhibition, a potential beneficial effect in this group of pregnancy-associated TMAs and p-aHUS is presumed., Conclusion: Based on our findings, we suggest a pragmatic approach toward limited and short-term anticomplement therapy for patients with a clinical diagnosis of p-aHUS, which should be stopped once causes of TMA other than genetic complement abnormalities emerge., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Background: The von Willebrand factor-directed nanobody caplacizumab has greatly changed the treatment of immune thrombotic thrombocytopenic purpura (iTTP) in recent years. Data from randomized controlled trials established efficacy and safety., Objectives: This study aims to address open questions regarding patient selection, tailoring of therapy duration, obstacles in prescribing caplacizumab in iTTP, effect on adjunct treatment, and outcomes in the real-world setting., Methods: We report retrospective, observational cohorts of 113 iTTP episodes treated with caplacizumab and 119 historical control episodes treated without caplacizumab. We aggregated data from the caplacizumab phase II/III trials and real-world data from France, the United Kingdom, Germany, and Austria (846 episodes, 396 treated with caplacizumab, and 450 historical controls)., Results: Caplacizumab was efficacious in iTTP, independent of the timing of therapy initiation, but curtailed the time of active iTTP only when used in the first-line therapy within 72 hours after diagnosis and until at least partial ADAMTS13-activity remission. Aggregated data from multiple study populations showed that caplacizumab use resulted in significant absolute risk reduction of 2.87% for iTTP-related mortality (number needed to treat 35) and a relative risk reduction of 59%., Conclusion: Caplacizumab should be used in first line and until ADAMTS13-remission, lowers iTTP-related mortality and refractoriness, and decreases the number of daily plasma exchange and hospital stay. This trial is registered at www., Clinicaltrials: gov as #NCT04985318., Competing Interests: Declaration of competing interests L.A.V. received speaker honoraria and consultant fees from Sanofi-Genzyme and AstraZeneca. J.K. reports speaker honoraria and participation on advisory boards from Alexion, Sanofi, and Chiesi. W.M. reports grants from Takeda/Shire and CSL Behring and received speaker honoraria and consultant fees from Takeda/Shire and CSL Behring. P.T.B. received speaker honoraria and consultant fees from Sanofi-Genzyme, AstraZeneca, Alexion, Bayer, Travere, Pfizer, Novartis, Roche, and participated in advisory boards for Alexion, Sanofi-Genzyme, Novartis, Travere, and Bayer. He declares research funding from the German Research Foundation BR-2955/8. R.W. received speaker honoraria and consultant fees from Sanofi-Genzyme. He additionally declares research funding from the German Federal Ministry of Education and Research and the German Federal Ministry of Health. U.S. reports study fees and/or consultancy/advisory board fees from Chemocentryx/Vifor, Ablynx/Genzyme-Sanofi, Alexion, Travere, Alynlam Pharmaceuticals, and Allena Pharmaceuticals. J.M. received speaker honoraria and consultant fees from Ablynx, Alexion, and Sanofi-Genzyme. D.A.Eichenhauer has received speaker honoraria from Sanofi-Genzyme and Takeda. K.S. has received speaker honoraria from AbbVie, Merck, Pfizer, and Roche, consultant fees from AbbVie, Amgen, Bristol-Myers Squibb, Merck, Novartis, and Roche, and travel and congress fee compensation from AbbVie, Bristol-Myers Squibb, Celgene, Janssen Cilag, Lilly, and Servier. M.H. reports travel and congress fee compensation and speaker honoraria from Jazz Pharmaceuticals. P.K. reports travel support, participation in data safety monitoring boards and advisory boards, and consulting fees and/or speaker honoraria from Ablynx/Sanofi, Shire Roche, Novo Nordisk, CSL-Behring, and Biotest. F.B. reports speaker honoraria and consulting fees from Sanofi-Genzyme. A.G. reports consulting fees from Sanofi-Genzyme and Alexion and participation in advisory boards for Alexion. T.M. reports speaker honoraria from Sanofi-Aventis Deutschland GmbH. A.S. reports advisory board fees from Sanofi-Genzyme. K.S. reports speaker honoraria from AstraZeneca, Novartis, Takeda/Shire, and Vifor. M. K. reports speaker honoraria from Sanofi-Genzyme. All other authors report no conflict of interest., (Copyright © 2022 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Thrombotic microangiopathies (TMA) are rare diseases, which are defined by the triad microangiopathic hemolytic anemia, thrombocytopenia and organ damage, and are associated with high morbidity and mortality. The recognition of a TMA and the distinction of important differential diagnoses are key factors, particularly in a perioperative context and in routine clinical intensive care. The further differentiation of the different TMA subtypes, such as thrombotic thrombocytopenic purpura (TTP), Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) and atypical hemolytic uremic syndrome (aHUS), based on the underlying pathophysiology and the development of new targeted treatment options in recent years have significantly improved the prognosis. A close interdisciplinary cooperation between critical care specialists and specialist disciplines experienced in the treatment of TMA, is essential for a prompt diagnosis and the initiation of the appropriate treatment., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Competing Interests: The authors have no competing interests to declare that are relevant to the content of this article.

Patients with immune-mediated kidney diseases are at increased risk of severe coronavirus disease 2019 (COVID-19). The international rollout of COVID-19 vaccines has provided varying degrees of protection and enabled the understanding of vaccine efficacy and safety. The immune response to COVID-19 vaccines is lower in most patients with immune-mediated kidney diseases; either related to immunosuppression or comorbidities and complications caused by the underlying disease. Humoral vaccine response, measured by the presence of antibodies, is impaired or absent in patients receiving rituximab, mycophenolate mofetil (MMF), higher doses of glucocorticoids and likely other immunosuppressants, such as cyclophosphamide. The timing between the use of these agents and administration of vaccines is associated with the level of immune response: with rituximab, vaccine response can only be expected once B cells start to recover and patients with transient discontinuation of MMF mount a humoral response more frequently. The emergence of new COVID-19 variants and waning of vaccine-induced immunity highlight the value of a booster dose and the need to develop mutant-proof vaccines. COVID-19 vaccines are safe, exhibiting a very low risk of de novo or relapsing immune-mediated kidney disease. Population-based studies will determine whether this is causal or coincidental. Such cases respond to standard management, including the use of immunosuppression. The Immunonephrology Working Group and European Vasculitis Society recommend that patients with immune-mediated kidney diseases follow national guidance on vaccination. Booster doses based on antibody measurements could be considered., Competing Interests: The authors have no financial or non-financial potential conflicts of interest to declare related to this project. K.I.S. has received honoraria from Bayer Pharmaceuticals. H.J.A. received honoraria or lecture fees from AstraZeneca, Bayer, Eleva, GlaxoSmithKline, Kezar, Eli Lilly, Novartis, Otsuka, Previpharma and Vifor. A.B. has received honoraria or consulting fees from AstraZeneca, Bayer, ChemoCentryx, Merck/MSD and Vifor. U.S. received honoraria or consulting fees from Ablynx/Sanofi, Alexion Pharma, Allena Pharmaceuticals and Chemocentryx/Vifor. S.P.M. has received honoraria and/or consultancy fees from GlaxoSmithKline, Vifor, Travere and Celltrion. D. Geetha received consulting fees from ChemoCentryx and Aurinia. D.R.W.J. received honoraria or consulting fees from Amgen, Astra-Zeneca, Aurinia, Bristol-Myers Squibb, Boehringer Ingelheim, Chemocentryx, GlaxoSmithKline, National Institute for Health and Care Excellence, Novartis, Otsuka, Roche/Genentech, Takeda, UCB and Vifor. A.K. received honoraria for consulting from Alexion, Otsuka, Catalyst Biosciences, UriSalt, Vifor Pharma and Delta 4 and speaking fees from Vifor Pharma and TerumoBCT. All others report no conflicts of interest related to COVID-19 vaccines., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Kidney transplantation is the best treatment option for patients with end-stage kidney disease (ESKD) with a superiority of graft survival after living kidney donation (LKD) compared to deceased donation. However, a large part of potential donors and recipients are ineligible for LKD. Here, we analyze the leading causes for disqualification of potential living donor-recipient pairs from the LKD program and the health-related consequences for ESKD patients excluded from the LKD program in a German transplant center., Methods: In this single-center retrospective cohort study we evaluated all candidates (potential donors and recipients) presenting for assessment of LKD from 2012 to 2020 at our transplant center. Thereby we focused on candidates excluded from the LKD program. Main reasons for disqualification were categorized as medical (donor-related), psychosocial, immunological, recipient-related, and unknown., Results: Overall, 601 donor-recipient pairs were referred to our transplant center for LKD assessment during the observation time. Out of those, 326 (54.2%) discontinued the program with 52 (8.7%) dropouts and 274 (45.6%) donor-recipient pairs being ineligible for LKD. Donor-related medical contraindications were the main reason for disqualification [139 out of 274 (50.7%) potential donors] followed by recipient-related contraindications [60 out of 274 (21.9%) of potential donor-recipient pairs]. Only 77 out of 257 (29.9%) potential recipients excluded from the LKD program received a kidney transplant afterward with a median waiting time of 2 (IQR: 1.0-4.0) years. Overall, 18 (7.0%) ESKD patients initially declined for LKD died in this period., Conclusion: A large percentage of donor-recipient pairs are disqualified from the German LKD program, mostly due to medical reasons related to the donor and with partly severe consequences for the potential recipients. For these, alternative solutions that promptly enable kidney transplantation are essential for improving patient quality of life and survival., 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 Grigorescu, Kemmner, Schönermarck, Sajin, Guenther, Cerqueira, Illigens, Siepmann, Meiser, Guba, Fischereder and Stang.)

Background/objectives: Autoimmune diseases are often associated with human leukocyte antigen (HLA) haplotypes, indicating that changes in major histocompatibility complex (MHC)-dependent self-peptide or antigen presentation contribute to autoimmunity. In our study, we aimed to investigate HLA alleles in a large European cohort of autoimmune pancreatitis (AIP) patients., Methods: Hundred patients with AIP, diagnosed and classified according to the International Consensus Diagnostic Criteria (ICDC), were prospectively enrolled in the study. Forty-four patients with chronic pancreatitis (CP) and 254 healthy subjects served as control groups. DNA was isolated from blood samples and two-digit HLA typing was performed with sequence-specific primer (SSP-) PCR. HLA allele association strength to AIP was calculated as odds ratio., Results: We uncovered a strong enrichment of HLA-DQB1 homozygosity in type 1 and type 2 AIP patients. Moreover, a significantly increased incidence of the HLA-DRB1∗16 and HLA-DQB1∗05 alleles and a concomitant lack of the HLA-DRB1∗13 allele was detected in AIP type 1 and type 2 patients. In contrast, the HLA-DQB1∗02 allele was underrepresented in the 'not otherwise specified' (NOS) AIP subtype. We detected no significant difference in the HLA-DRB3, HLA-DRB4 and HLA-DRB5 allele frequency in our cohort., Conclusions: Although AIP type 1 and type 2 are characterized by distinct histopathological characteristics, both subtypes are associated with the same HLA alleles, indicating that the disease might rely on similar immunogenic mechanisms. However, AIP NOS represented another subclass of AIP., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Short-term studies have shown an attenuated immune response in hemodialysis patients after COVID-19-vaccination. The present study examines how antibody response is maintained after vaccination against SARS-CoV-2 in a large population of hemodialysis patients from six outpatient dialysis centers. We retrospectively assessed serum antibody levels against SARS-CoV-2 spike protein and nucleocapsid protein (electrochemiluminescence immunoassays, Roche Diagnostics) after COVID-19-vaccination in 298 hemodialysis and 103 non-dialysis patients (controls), comparing early and late antibody response. Compared to a non-dialysis cohort hemodialysis patients showed a favorable but profoundly lower early antibody response, which decreased substantially during follow-up measurement (median 6 months after vaccination). Significantly more hemodialysis patients had anti-SARS-CoV-2-S antibody titers below 100 U/mL (p < 0.001), which increased during follow-up from 23% to 45% but remained low in the control group (3% vs. 7%). In multivariate analysis, previous COVID-19 infections (p < 0.001) and female gender (p < 0.05) were significantly associated with higher early as well as late antibody vaccine response in hemodialysis patients, while there was a significant inverse correlation between patient age and systemic immunosuppression (p < 0.001). The early and late antibody responses were significantly higher in patients receiving vaccination after a SARS-CoV-2 infection compared to uninfected patients in both groups (p < 0.05). We also note that a higher titer after complete immunization positively affected late antibody response. The observation, that hemodialysis patients showed a significantly stronger decline of SARS-CoV-2 vaccination antibody titers within 6 months, compared to controls, supports the need for booster vaccinations to foster a stronger and more persistent antibody response.

Background: The anti-von Willebrand factor (VWF) nanobody caplacizumab directly prevents the fatal microthrombi formation in immune-mediated thrombotic thrombocytopenic purpura (iTTP), thereby adding a new therapeutic principle to the treatment of this disorder. However, real-world treatment modalities beyond clinical trials remain heterogeneous., Methods: Here, we describe the risks and benefits of an alternate-day dosing regimen for caplacizumab by thoroughly analyzing the timing and outcome of this approach in a retrospective cohort of 25 iTTP patients treated with caplacizumab at seven different medical centers in Austria and Germany between 2018 and 2021., Results: Alternate-day dosing of caplacizumab appeared feasible and led to persisting normal platelet counts in most patients. Five patients experienced iTTP exacerbations or relapses that led to the resumption of daily caplacizumab application. VWF activity was repeatedly measured in 16 of 25 patients and documented sufficient suppression by caplacizumab after 24 and 48 h in line with published pharmacodynamics., Conclusion: Extension of caplacizumab application intervals from daily to alternate-day dosing may be safely considered in selected patients after 3 to 4 weeks of daily treatment. Earlier modifications may be discussed in low-risk patients but require close monitoring for clinical and laboratory features of thrombotic microangiopathy., (© 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Objectives: Acute kidney injury (AKI) following surgery involving the heart-lung-machine is associated with high mortality and morbidity. In addition to the known mechanisms, thrombotic microangiopathy (TMA) triggered by the dysregulation of complement activation was recently described as another pathophysiological pathway for AKI following aortic surgery. The aim of this retrospective study was to analyse incidence, predictors and outcome in these patients., Methods: Between January 2018 and September 2019, consecutive patients undergoing aortic surgery requiring hypothermic circulatory arrest were retrospectively reviewed. If suspected, diagnostic algorithm was initiated to identify a TMA and its risk factors, and postoperative outcome parameters were comparably investigated., Results: The incidence of TMA in the analysed cohort (n = 247) was 4.5%. Multivariable logistic regression indicated female gender {odds ratio (OR) 4.905 [95% confidence interval (CI) 1.234-19.495], P = 0.024} and aortic valve replacement [OR 8.886 (95% CI 1.030-76.660), P = 0.047] as independent predictors of TMA, while cardiopulmonary bypass, X-clamp and hypothermic circulatory arrest times showed no statistically significance. TMA resulted in postoperative AKI (82%), neurological disorders (73%) and thrombocytopaenia [31 (interquartile range 25-42) G/l], corresponding to the diagnostic criteria. Operative mortality and morbidity were equal to patients without postoperative TMA, despite a higher incidence of re-exploration for bleeding (27 vs 6%; P = 0.027). After 6 months, survival, laboratory parameters and need for dialysis were comparable between the groups., Conclusions: TMA is a potential differential diagnosis for the cause of AKI following aortic surgery regardless of the hypothermic circulatory arrest time. Timely diagnosis and appropriate treatment resulted in a comparable outcome concerning mortality and renal function., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction: Chronic kidney disease (CKD) is associated with significant morbidity and mortality after lung transplantation (LTX). Calcineurin inhibitor (CNI) nephrotoxicity is the leading cause of CKD. After kidney transplantation, polyomavirus-associated nephropathy (PyVAN) is a well-recognized problem. This study aims to evaluate the role of polyomavirus in patients after LTX., Methods: From January 2017 to January 2020, all lung transplant recipients who performed follow-up visits in our center were included in the study and retrospectively assessed. We measured renal function (creatinine levels before and after transplantation), JCPyV, and BKPyV load by polymerase chain reaction (PCR) in serum and urine samples after transplantation., Results: In total, 104 consecutive patients (59 males, 56.7%) with a mean age of 49.6 ± 11.1 years were identified. JCPyV was found in urine of 36 patients (34.6%) and serum of 3 patients (2.9%). BKPyV was found in urine of 40 patients (38.5%) and serum of 4 patients (3.8%), respectively. Urine evidence for JCPyV (p < 0.001, coefficient: +21.44) and BKPyV (p < 0.001, coefficient: +29.65) correlated highly with further kidney function decline., Conclusion: Kidney function deterioration is associated with JCPyV and BKPyV viruria in patients after LTX. This might indicate a role of PyVAN in lung transplant recipients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The Coronavirus Disease 2019 (COVID-19) pandemic influenced the management of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A paucity of data exists on outcome of patients with vasculitis following COVID-19, but mortality is higher than in the general population and comparable to patients undergoing haemodialysis or kidney transplant recipients (reported mortality rates of 20-25%). Delays in diagnosis have been reported, which are associated with sequelae such as dialysis-dependency. Management of ANCA-associated vasculitis has not changed with the aim to suppress disease activity and reduce burden of disease. The use of rituximab, an important and widely used agent, is associated with a more severe hospital course of COVID-19 and absence of antibodies following severe acute respiratory syndrome (SARS)-CoV-2 infections, which prone patients to re-infection. Reports on vaccine antibody response are scarce at the moment, but preliminary findings point towards an impaired immune response, especially when patients receive rituximab as part of their treatment. Seropositivity was reported in less than 20% of patients when rituximab was administered within the prior six months, and the antibody response correlated with CD19 + B-cell repopulation. A delay in maintenance doses, if disease activity allows, has been suggested using a CD19 + B-cell guided strategy. Other immunosuppressive measures, which are used in ANCA-associated vasculitis, also impair humoral and cellular vaccine responses. Regular measurements of vaccine response or a healthcare-policy time-based strategy are indicated to provide additional doses ("booster") of COVID-19 vaccines. This review summarizes a recent educational forum and a recent virtual meeting of the European Vasculitis Society (EUVAS) focusing on COVID-19., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In 2021 new KDIGO (Kidney Disease: Improving Global Outcomes) guidelines for the management of glomerular diseases were published.For ANCA-associated glomerulonephritis the new recommendations comprise a more rapid steroid taper during induction treatment with cyclophosphamide or rituximab, the advice against routine use of plasma exchange, the choice of drug for and duration of maintenance treatment in accordance with predictors of relapse. A kidney transplant should be performed after at least 6 months of remission irrespective of the ANCA titer in ANCA-associated disease, and 6 months after absence of anti-GBM-antibodies in anti-GBM-disease., Competing Interests: K. de Groot: Beratungsgremium/Advisory Board (Vifor, Roche); Forschungsunterstützung (–);Vortragshonorare (Vifor, Roche, Böhringer Ingelheim, Forum für Medizinische Fortbildung, streamed-up);Mitgliedschaften (DGfN, DGRh, EULAR, EUVAS, ASN)M. Haubitz: Beratungsgremium/Advisory Board (Bayer, Roche); Forschungsunterstützung (–);Vortragshonorare (Hexal, Fresenius, Berlin-Chemie), (Streamed-up, Rheumatologische Fortbildungsakademie), SpringerMedizin (Editor für Heft, Editor-Board);Mitgliedschaften (DGfN, ERA-EDTA, EUVAS)H. Rupprecht: Beratungsgremium/Advisory Board (–);Forschungsunterstützung (–);Vortragshonorare (Alexion, Novartis, Brystol-Myers Squibb, AstraZeneca, Amgen), (med update GmbH, Akademie Niere, Rhein Main AG für Nephrologie, Forum für Medizinische Fortbildung);Mitgliedschaften (DGfN, ERA-EDTA)U. Schönermarck: Beratungsgremium/Advisory Board (Ablynx, Alexion, Chemocentryx/Vifor);Forschungsunterstützung (Chemocentryx/Vifor, Ablynx/Sanofi, Alexion);Vortragshonorare (Vifor, Alexion), (Forum für Medizinische Fortbildung);Mitgliedschaften (DGfN, ERA-EDTA, EUVAS, ASN), (Thieme. All rights reserved.)