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Anti-SARS-CoV-2 vaccination of dialysis patients has been proven to be safe and effective to reduce COVID-19-related morbidity and mortality. However, data on the durability of anti-SARS-CoV-2 antibodies post-vaccination in peritoneal dialysis (PD) patients are scarce. In this prospective single-center cohort study we measured anti-SARS-CoV-2 RBD antibodies 3 and 6 months after the 3rd dose of the mRNA-1273 vaccine in 27 adult PD patients and recorded breakthrough infections. Furthermore, in a mixed model analysis, we analyzed potential factors influencing the humoral response following vaccination. Anti-SARS-CoV-2 RBD antibody levels declined from 21,424 BAU/mL at 1 month to 8397 BAU/mL at 3 months and to 5120 BAU/mL at 6 months after the 3rd dose, but remained higher than pre-3rd dose levels (212 BAU/mL). Eight patients (29.6%) were infected with SARS-CoV-2 within six months from the 3rd dose during the Omicron wave. Previous high antibody levels, high glomerular filtration rate (GFR) and low Davies Comorbidity Score were associated with higher anti-SARS-CoV-2 antibody levels after the booster. In conclusion, PD patients exhibited a robust and durable humoral response after a third dose of the mRNA-1273 vaccine. A high GFR and low comorbidity as well as previous high antibody levels predicted a better humoral response to vaccination.

In dialysis patients the humoral response to anti-SARS-CoV-2 vaccines is attenuated and rapidly declines over time. However, data on the persistence of the immune response in peritoneal dialysis (PD) patients are scarce, particularly after a third (booster) dose with mRNA-1273 vaccine. In this prospective cohort study, we report anti-SARS-CoV-2 antibody levels in PD patients before and after the third dose of mRNA-1273 vaccine. Six months after the second dose, anti-SARS-CoV-2 antibodies were detected in all patients ( n = 34). However, within this time period antibodies substantially declined in 31 of 34 patients (4.5-fold, median = 192 BAU/mL, p = 1.27 × 10 -9 ) and increased in three patients. In accordance with government regulations, a third dose of mRNA-1273 vaccine (50 μg) was given to 27 PD patients 6 months after the second dose which induced a significant increase of anti-SARS-CoV-2 antibody titers (58.6-fold, median = 19405 BAU/mL, p = 1.24 × 10 -29 ). A mixed model analysis showed that a lower Davies Comorbidity Score and a higher GFR were associated with higher antibody titers ( p = 0.03 and p = 0.02). The most common adverse events after the third dose were pain at the injection site (77.8%) and fatigue (51.9%). No hospitalizations were reported. In conclusion, 6 months after the second dose of mRNA-1273 vaccine, anti-SARS-CoV-2 antibodies substantially decreased in PD patients, whereas a well-tolerated third dose induced a robust humoral response. Our data suggest that the administration of a booster dose within a shorter interval than 6 months should be considered in PD patients in order to maintain high anti-SARS-CoV-2 antibody levels and assure protection from severe COVID-19 disease., 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 Beilhack, Monteforte, Frommlet, Reindl-Schwaighofer, Strassl and Vychytil.)

Background: Dialysis patients are at high risk for a severe clinical course after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Safety and early immune responses after mRNA-based vaccination have been reported mostly in patients on hemodialysis (HD), whereas reports of peritoneal dialysis (PD) patients remain rare., Methods: In this retrospective observational study, 39 PD patients had received two doses of the mRNA-1273 Moderna ® vaccine. We analyzed SARS-CoV-2 Spike (S) antibody titers 4 weeks after each dose of mRNA-1273 and report local and systemic side effects in PD patients that occurred within one week after each mRNA-1273 dose. Using a quantile regression model we examined factors that might influence SARS-CoV-2 S antibody levels in PD patients., Results: Four weeks after the first dose of mRNA-1273 vaccine 33 of 39 (84.6%) PD patients seroconverted and presented with 6.62 U/mL (median; IQR 1.57-22.5) anti-SARS-CoV-2 S antibody titers. After the second dose, 38 of 39 (97.4%) PD patients developed anti-SARS-CoV-2 S antibodies and titers increased significantly (median 968 U/mL; IQR 422.5-2500). Pain at the injection site was the most common local adverse event (AE) (71%). Systemic AEs occurring after the first dose were mostly fatigue (33%) and headache (20%). No severe systemic AEs were reported after the first injection. After the second dose the incidence and the severity of the systemic AEs increased. The most common systemic AEs were: fatigue (40.5%), headache (22.5%), joint pain (20%), myalgia (17.5%) and fever (13%). Lower Davies Comorbidity Score (p=0.04) and shorter dialysis vintage (p=0.017) were associated with higher antibody titers after the first dose. Patients with higher antibody titers after the first dose tended to have higher antibody titers after the second dose (p=1.53x10 -05 )., Conclusions: Peritoneal dialysis patients in this cohort had a high seroconversion rate of 97.4%, showed high antibody titers after full vaccination and tolerated the anti-SARS-CoV-2 mRNA-1273 vaccine well without serious adverse events., 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 © 2021 Beilhack, Monteforte, Frommlet, Gaggl, Strassl and Vychytil.)

Background: Acid base and electrolyte disorders are frequently reported in the early period after renal transplantation. No comprehensive data exist on the prevalence and patterns of, and contributing factors to, electrolyte disturbances in patients with stable long-term allograft function., Methods: We analysed 576 renal transplant recipients (serum creatinine level <2.0 mg/dl) in a cross-sectional study to evaluate the prevalence of electrolyte disorders and the risk factors associated with their occurrence., Results: A total of 369 patients (64%) of all allograft recipients (n = 576) showed at least one electrolyte and acid base disorder. The most abundant disorder was hypomagnesaemia (25%, n = 143), followed by hyperkalaemia (12.8%, n = 74), hypercalcaemia (12%, n = 69), hypophosphataemia (11.6%, n = 67), metabolic acidosis (11.1%, n = 61) and hyponatraemia (9%, n = 52). All other electrolyte disorders were rare (<6%). In most cases the electrolyte disorders could be classified as mild. Forty percent of the cases had a combined disorder, but without a preferential pattern of combinations. In a multivariate logistic regression analysis, the most important factors contributing significantly to the occurrence of electrolyte disorders were renal function and concomitant medications., Conclusion: Acid base and electrolyte disorders are frequently observed in stable renal allograft recipients, but are usually mild. A combination of two or more electrolyte abnormalities often occurs, although no predominant pattern of a unique combination of electrolyte disorder is recognizable. &nbsp.

Background: Complement factor C3 represents the central component of the complement cascade and its activation split product C3a plays an important role in inflammation and disease. Many human disorders are linked to dysregulation of the complement system and alteration in interaction molecules. Therefore, various therapeutic approaches to act on the complement system have been initiated., Methods and Results: Aiming to develop a tool to eliminate C3a/C3 from the circulation, in a first step a high affine murine monoclonal antibody (mAb) (3F7E2-mAb) was generated against complement factor C3 and selected for binding to the C3a region to serve as immunoaffinity reagent. Functional testing of the 3F7E2-mAb revealed an inhibition of Zymosan-induced cleavage of C3a from C3. Subsequently, a C3a/C3 specific 3F7E2-immunoaffinity column was developed and apheresis of C3a/C3 and associates was performed. Finally, a proteomic analysis was carried out for identification of apheresis products. C3a/C3 was liberated from the 3F7E2-column together with 278 proteins. C3a/C3 interaction specificity was validated by using a haptoglobin immunoaffinity column as control and biostatistic analysis revealed 39 true C3a/C3 interactants., Conclusion: A novel and functionally active mAb was developed against complement factor C3a/C3 and used in a specific immunoaffinity column that allows apheresis of C3a/C3 and associates and their identification by proteomic analysis. This methodological approach of developing specific antibodies that can be used as immunoaffinity reagents to design immunoaffinity columns for elimination and further identification of associated proteins could open new avenues for the development of tailored immunotherapy in various complement-mediated or autoimmune diseases., Competing Interests: The authors declare that they have no competing interests., (© 2019 Winnicki et al.)

Current vaccine conditions predominantly elicit low-avidity cytotoxic T lymphocytes (CTLs), which are non-tumor-cytolytic but indistinguishable by tetramer staining or enzyme-linked immunospot from high-avidity CTLs. Using CTL clones of high or low avidity for melanoma antigens, we show that low-avidity CTLs can inhibit tumor lysis by high-avidity CTLs in an antigen-specific manner. This phenomenon operates in vivo: high-avidity CTLs control tumor growth in animals but not in combination with low-avidity CTLs specific for the same antigen. The mechanism involves stripping of specific peptide-major histocompatibility complexes (pMHCs) via trogocytosis by low-avidity melanoma-specific CTLs without degranulation, leading to insufficient levels of specific pMHC on target cell surface to trigger lysis by high-avidity CTLs. As such, peptide repertoire on the cell surface is dynamic and continually shaped by interactions with T cells. These results describe immune regulation by low-avidity T cells and have implications for vaccine design., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: In chronic kidney disease-mineral and bone disorder (CKD-MBD), most treatment decisions are guided by parathyroid hormone (PTH) levels. Here, we aimed at assessing the technical and clinical performance of two novel automated biointact PTH(1-84) assays, from Roche Diagnostics (Ro) and DiaSorin (DS), in hemodialysis patients., Design and Methods: We recorded demographics, dialysis treatment characteristics, pharmacotherapy for CKD-MBD and laboratory work-up. Statistical methods included Passing-Bablok, and multiple linear regression., Results: 121 patients, dialyzing on average for 3.5 years (range: 0.1-22.5), with serum phosphate 1.9±0.6 mmol/L (mean±SD), participated in the study. Median serum concentration for intact PTH was 223 ng/L (range: 5-2844), and for biointact PTH(1-84) was 136 ng/L (Ro; range: 1-1644), respectively 138 ng/L (DS; range: 4-1580). Both biointact assays were significantly correlated (r=0.98; Ro=0.87×DS+19.60). Bland-Altmann plots revealed an average bias ±2 SD of 10±27 ng/L below 200 ng/L, and -32±157 ng/L above 200 ng/L (Ro minus DS). The variably adjusted association between PTH and serum phosphate was very similar, regardless of the PTH assay, but this was not the case for PTH-derived measures (ratios biointact/intact; differences intact minus biointact). (Log)PTH concentrations as well as serum phosphate were significantly associated with serum creatinine, but only in patients with >0 mL urine per day., Conclusions: Results from Roche and DiaSorin biointact PTH(1-84) assays were well correlated, but showed increased deviations at higher concentrations. Biointact PTH(1-84) levels are roughly two third of intact PTH. The association between PTH and serum creatinine may depend on residual renal clearance of PTH and/or serum phosphate., (Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)