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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.)

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.)

Background: Some studies have shown an attenuated immune response in haemodialysis patients after vaccination. The present study examines the humoral response after mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large population of haemodialysis patients from different outpatient dialysis centres., Methods: We retrospectively assessed antibodies against SARS-CoV-2 spike protein and nucleocapsid protein (chemiluminescence immunoassays, Roche diagnostics) 3-6 weeks after the second mRNA vaccine dose in 179 maintenance haemodialysis and 70 non-dialysis patients (control cohort). Differences in anti-SARS-CoV-2 spike protein titers were statistically analysed with respect to patient-relevant factors, including age, gender, previous coronavirus disease 2019 (COVID-19) infection, systemic immunosuppressive therapy and time on dialysis., Results: We found a favourable, but profoundly lower SARS-CoV-2 spike protein antibody response in comparison with a non-dialysis cohort (median 253.5 versus 1756 U/mL, P < 0.001). In multivariate analysis, previous COVID-19 infection (P < 0.001) and female gender were associated with a significantly higher vaccine response (P = 0.006) in haemodialysis patients, while there was a significant inverse correlation with increasing patient age and systemic immunosuppression (P < 0.001). There was no statistically significant correlation between the antibody titer and time on dialysis. Immune response in haemodialysis patients with a previous COVID-19 infection led to substantially higher antibody titers that were equal to those of vaccinated non-dialysis individuals with previous infection., Conclusion: We strongly argue in favour of regular antibody testing after COVID-19 vaccination in haemodialysis patients. Further studies should elucidate the utility of booster vaccinations to foster a stronger and persistent antibody response., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Data are lacking on the relative incidence of thrombotic thrombocytopenic purpura (TTP), haemolytic uraemic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) and atypical HUS (aHUS) in patients presenting with thrombotic microangiopathies (TMAs)., Methods: This was a prospective, cross-sectional, multicentre and non-interventional epidemiological study. Patients fulfilling criteria for TMAs (platelet consumption, microangiopathic haemolytic anaemia and organ dysfunction) were included in the study. The primary objective was to assess the relative incidence of TTP, STEC-HUS, aHUS and 'other' physician-defined diagnoses. The secondary objective was to develop an algorithm to predict a severe deficiency in ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity (≤10%) using routine laboratory parameters. A post hoc classification using the recent Kidney Disease: Improving Global Outcomes diagnostic criteria was then undertaken to further classify patient groups., Results: aHUS was diagnosed with a relative incidence of 61%, whereas TTP, STEC-HUS and 'other' were diagnosed in 13, 6 and 20% of patients, respectively. In the post hoc analysis, 27% of patients with a TMA were classified as 'primary aHUS' and 53% as 'secondary aHUS'. Multivariate analysis revealed that severe deficiency in ADAMTS13 activity (≤10%) was unlikely to underlie TMA if platelet and serum creatinine were above threshold values of 30 × 10 9 /L and 1.8 mg/dL, respectively (negative predictive value of 92.3 and 98.1, respectively, if one or both values were above the threshold)., Conclusions: In this study, aHUS was the most common single diagnosis among patients presenting with a TMA. In the absence of an ADAMTS13 activity result, platelet count and serum creatinine may aid in the differential diagnosis., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Anti-neutrophil cytoplasmic autoantibodies (ANCA) with specificity for proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) are a defining feature of ANCA-associated vasculitides (AAV). They play a pivotal role in disease pathophysiology and have strongly improved early diagnosis and treatment of these infrequent, but potentially fatal diseases. Neutrophils and their products are major players in initiating the autoimmune response and tissue destruction in vasculitic as well as granulomatous inflammation. This review highlights recent findings on old and novel players (ANCA, neutrophils, neutrophil extracellular traps, fibroblasts, immune cells and complement) and puts them into context with the current understanding of disease mechanisms in AAV., (© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Transcatheter aortic valve implantation (TAVI) has emerged as a new therapeutic option for surgical high-risk patients with severe aortic stenosis (AS). Many of these patients suffer from chronic kidney disease (CKD), which substantially increases the risk for acute kidney injury (AKI), need for renal replacement therapy (RRT) and mortality after surgical aortic valve repair. The impact of pre-existing CKD for the outcome of TAVI is still unclear., Methods: We retrospectively evaluated 199 consecutive patients with symptomatic high-grade AS undergoing TAVI with the CoreValve prosthesis at our centre. We analysed incidence and predictive factors for AKI, RRT and mortality in patients with and without CKD (defined as an estimated glomerular filtration rate <60 mL/min)., Results: 26.8% of the patients suffered from AKI, 4.9% needed RRT and 5.5% died. All patients on chronic haemodialysis (n = 10) survived. There were no significant differences between patients with or without CKD concerning the incidence of AKI, RRT and mortality. Age, peripheral vascular disease and the need for blood transfusion were independently associated with AKI. AKI proved to be a predictive factor for mortality., Conclusions: Transcatheter aortic valve replacement with the CoreValve prosthesis does not seem to bear an increased risk for patients with CKD. For surgical high-risk patients with severe AS, a more liberal consideration for TAVI as an alternative to open surgery might be justified.

Objectives: To evaluate the prevalence and association of antineutrophil cytoplasmic antibodies (ANCA) and their subtypes [proteinase 3 (PR3)-ANCA, myeloperoxidase (MPO)-ANCA] with distinct clinical features in various clinicopathological syndromes., Methods: All consecutive ANCA-positive patients seen at the combined unit for rheumatology for Bad Bramstedt and the University of Lübeck between 1989 and 1999 were analysed. ANCA were detected by an immunofluorescence technique and ANCA subspecificities were determined by ELISA. Clinical features at presentation and diagnoses were recorded according to standardized procedures., Results: Among 4620 patients tested, 333 were cytoplasmic ANCA-positive and 291 were perinuclear ANCA-positive. cANCA/PR3-ANCA were strongly associated with Wegener's granulomatosis (WG), whereas pANCA/MPO-ANCA were associated with a diverse disease spectrum. Further investigation of PR3-ANCA-positive (n=80) and MPO-ANCA-positive patients (n=40) revealed a greater extent of disease [disease extent index (DEI); median 8 vs 5, P<0.01] and more frequent involvement of the upper/lower respiratory tract and the eyes in PR3-ANCA-positive than in MPO-ANCA-positive patients. Fewer than 5% of WG patients were MPO-ANCA-positive. Compared with matched PR3-ANCA-positive WG patients, the MPO-ANCA-positive WG patients had a lower DEI (median 5 vs 8) and had a lower frequency of peripheral neuropathy., Conclusions: ANCA testing is useful due to its high sensitivity and specificity, especially for cANCA/PR3-ANCA in WG. We found a divergence in the disease spectrum between PR3- and MPO-ANCA-positive patients, characterized by higher DEI and extrarenal manifestations in the PR3-ANCA group. MPO-ANCA was rarely found in WG and was associated with less organ involvement.