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Background: Access to deceased donor kidney transplantation may be restricted in the event of resource limitation induced by extreme peaks in activity or local major incidents, which exceed centre capacity. An organ-sharing protocol was developed by the five London transplant units in 2019 to establish a system for safe transfer of organs and recipients between five regional kidney transplant units. We describe the activity and outcomes over the initial 20-month period., Methods: National data on kidney transplants performed via the collaborative scheme were obtained from National Health Service Blood and Transplant. Outcomes data was collected locally and analysed., Results: Sixteen recipients were transplanted between November 2020 and July 2022. The reasons for referral were theatre capacity and an information technology systems failure. Donor kidneys were from 10 brainstem death donors (62.5%) and six circulatory death donors (37.5%). Half of the donors fulfilled standard criteria. Twelve patients (75%) were first transplant recipients. Three (18.75%) were highly sensitized (calculated reaction frequency ≥85%). Three (18.75%) patients required arterial reconstruction. Seven patients (43.75%) had delayed graft function. Median creatinine at 12 months post-transplantation was 134 µmol/L. The median length of stay was 7.5 days. Three recipients (18.75%) died within the first year, two from SARS-CoV-2 infection., Conclusions: This unique organ sharing collaborative scheme involving five hospitals in London enabled 16 transplants to proceed which otherwise would not have occurred. Although initially established for low-risk donors and recipients, the scheme has evolved to enable transplantation for a wide variety of recipients of varying complexity., Competing Interests: The authors have no conflicts of interests to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

The COVID-19 pandemic represented 1 of the more significant and unique public health challenges facing the global community, particularly afflicting those with compromised immune systems. These immunocompromised individuals were readily recognized as a group at high risk of infection by SARS-CoV-2 and the associated severe outcomes of COVID-19. Although preventive strategies such as vaccination are important, initial clinical vaccine trials did not enroll immunocompromised individuals; in-depth evaluations of the safety, immunogenicity, and real-world outcomes associated with these vaccines were conducted in this population thereafter. As immunogenicity data of COVID-19 vaccination among this disparate group of individuals emerged, vaccination strategies were adapted to address outstanding challenges and further protect the entirety of this population. This 8-part journal supplement characterizes in-depth the mRNA-based COVID-19 vaccination strategies across the spectrum of immunocompromised individuals, focusing on the ongoing approaches to challenges facing this group as the pandemic continues to evolve., Competing Interests: Potential conflicts of interest . M. W. has received speaker’s fees from AstraZeneca. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The diagnosis of antibody-mediated rejection (AMR) is reached using the Banff Classification for Allograft Pathology, which now includes gene expression analysis. In this study, we investigate the application of 'increased expression of thoroughly validated gene transcripts/classifiers strongly associated with AMR' as diagnostic criteria., Method: We used quantitative real-time polymerase chain reaction for 10 genes associated with AMR in a retrospective cohort of 297 transplant biopsies, including biopsies that met the full diagnostic criteria for AMR, even without molecular data (AMR, n = 27), biopsies that showed features of AMR, but that would only meet criteria for AMR with increased transcripts [suspicious for AMR (AMRsusp), n = 49] and biopsies that would never meet criteria for AMR (No-AMR, n = 221)., Results: A 10-gene AMR score trained by a receiver-operating characteristic to identify AMR found 16 cases with a high score among the AMRsusp cases (AMRsusp-high) that had significantly worse graft survival than those with a low score (AMRsusp-low; n = 33). In both univariate and multivariate Cox regression analysis, the AMR 10-gene score was significantly associated with an increased hazard ratio (HR) for graft loss (GL) in the AMRsusp group (HR = 1.109, P = 0.004 and HR = 1.138, P = 0.012, respectively), but not in the whole cohort. Net reclassification index and integrated discrimination improvement analyses demonstrated improved risk classification and superior discrimination, respectively, for GL when considering the gene score in addition to histological and serological data, but only in the AMRsusp group, not the whole cohort., Conclusions: This study provides evidence that a gene score strongly associated with AMR helps identify cases at higher risk of GL in biopsies that are suspicious for AMR but do not meet full criteria., Competing Interests: C.R. has a consultancy agreement with UCB., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA.)

Protease inhibitors influence a range of innate immunity and inflammatory pathways. We quantified plasma concentrations of key anti-inflammatory protease inhibitors in chronic haemodialysis patients with coronavirus disease 2019 (COVID-19). The samples were collected early in the disease course to determine whether plasma protease inhibitor levels associated with the presence and severity of COVID-19. We used antibody-based immunoassays to measure plasma concentrations of C1 esterase inhibitor, alpha2-macroglobulin, antithrombin and inter-alpha-inhibitor heavy chain 4 (ITIH4) in 100 serial samples from 27 haemodialysis patients with COVID-19. ITIH4 was tested in two assays, one measuring intact ITIH4 and another also detecting any fragmented ITIH4 (total ITIH4). Control cohorts were 32 haemodialysis patients without COVID-19 and 32 healthy controls. We compared protease inhibitor concentration based on current and future COVID-19 severity and with C-reactive protein. Results were adjusted for repeated measures and multiple comparisons. Analysis of all available samples demonstrated lower plasma C1 esterase inhibitor and α2M and higher total ITIH4 in COVID-19 compared with dialysis controls. These differences were also seen in the first sample collected after COVID-19 diagnosis, a median of 4 days from diagnostic swab. Plasma ITIH4 levels were higher in severe than the non-severe COVID-19. Serum C-reactive protein correlated positively with plasma levels of antithrombin, intact ITIH4 and total ITIH4. In conclusion, plasma protease inhibitor concentrations are altered in COVID-19., (© The Author(s) 2021. Published by Oxford University Press.)

Background: Complement activation may play a pathogenic role in patients with severe coronavirus disease 2019 (COVID-19) by contributing to tissue inflammation and microvascular thrombosis., Methods: Serial samples were collected from patients receiving maintenance haemodialysis (HD). Thirty-nine patients had confirmed COVID-19 and 10 patients had no evidence of COVID-19. Plasma C5a and C3a levels were measured using enzyme-linked immunosorbent assay., Results: We identified elevated levels of plasma C3a and C5a in HD patients with severe COVID-19 compared with controls. Serial sampling identified that C5a levels were elevated prior to clinical deterioration in patients who developed severe disease. C3a more closely mirrored both clinical and biochemical disease severity., Conclusions: Our findings suggest that activation of complement plays a role in the pathogenesis of COVID-19, leading to endothelial injury and lung damage. C5a may be an earlier biomarker of disease severity than conventional parameters such as C-reactive protein and this warrants further investigation in dedicated biomarker studies. Our data support the testing of complement inhibition as a therapeutic strategy for patients with severe COVID-19., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Several publications have demonstrated the use of renal biopsy in elderly patients in establishing a diagnosis and enabling directed therapy. However, evidence on the long-term outcomes following biopsies is lacking. The aim of this study is to describe the renal and patient outcomes in elderly patients according to indication for biopsy, clinical parameters and the histological diagnosis., Methods: We performed a retrospective cohort study of 463 patients >70 years old who underwent a renal biopsy at our centre between 2006 and 2015., Results: The median age of the patients was 74.8 (range 70.0-89.6) years. The most frequent primary diagnoses were pauci-immune crescentic glomerulonephritis (GN; 12%), acute interstitial nephritis (10.8%) and membranous GN (7.1%). Death-censored renal survival at 1 and 5 years following the index biopsy was 85.2 and 75.9%, respectively, and patient survival at 1 and 5 years was 92.2 and 71.6%, respectively. Patients who progressed to end-stage renal disease (ESRD) were at higher risk of dying compared with patients who did not require dialysis [hazard ratio 2.41 (95% confidence interval 1.58-3.68; P < 0.001]. On multivariate analysis, factors associated with the risk of progression to ESRD were creatinine (P < 0.001), heavy proteinuria (P = 0.002) and a non-chronic kidney disease (CKD) biopsy indication (P = 0.006). A histological diagnosis of primary GN (P = 0.001) or tubulointerstitial nephritis (P = 0.008) was associated with a favourable renal outcome, while patients with vasculitis and paraprotein-related renal disease (PPRD) had the highest risk of requiring dialysis (P = 0.0002 and P = 0.003, respectively). PPRD was also an independent risk factor for death., Conclusions: This study demonstrates that renal biopsies in the elderly not only enable directed therapy, but also provide prognostic information on renal and patient survival.