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TFEB -altered renal cell carcinomas are rare tumours. Here, we report the exceptional case of such a tumour in the setting of solid organ transplantation and with already metastatic disease at the time of diagnosis. The primary tumour occurred in the native kidney and only focally showed biphasic morphology whereas the metastasis, among others to the transplant kidney, showed nonspecific, albeit different morphology, but both had consistent TFEB translocation. Treatment with the immune checkpoint inhibitor pembrolizumab together with the multi-kinase inhibitor lenvatinib achieved partial response 14 months after diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: The coronavirus disease-19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus is alleged to enable a proinflammatory state, that leads to the activation of the coagulation and the complement cascade. In this study, we aimed to establish the impact of the COVID-19 pandemic on patients with new onset of cTMA/aHUS in the Vienna TMA cohort and whether COVID-19 or SARS-CoV-2 vaccinations would pose a greater risk of initial manifestation of cTMA/aHUS., Methods: We used the Vienna TMA cohort database to examine the prevalence of COVID-19 related and of SARS-CoV-2 vaccination-related aHUS/cTMA during the first 3 years of the COVID-19 pandemic in a large single-center cohort., Results: Between March 2020 and May 2023, a total of 7 patients experienced their first aHUS/cTMA episode. No patient experienced a TMA relapse or more than one episode during the follow-up period. Three TMA episodes were attributable to either COVID-19 (n=1; 33%) or SARS-CoV-2 vaccination (n=2; 66%), respectively. All three patients had systemic signs of TMA and TMA was confirmed by kidney biopsy in all cases. Among the seven patients we recorded five infections that triggered one TMA episode (20%) and 19 vaccinations triggered two TMA episodes (10%; p=0.52, odds ratio 0.47; 95% CI 0.04-8.39)., Conclusion: We speculate, that both SARS-CoV-2 vaccinations and COVID-19 episodes can represent a triggering factor for aHUS/cTMA episodes in (genetically) vulnerable individuals. However, COVID-19 might have a stronger association and might be a stronger trigger than the SARS-CoV-2 vaccines. The incidence of new aHUS cases did not differ from the pre-pandemic era in a large tertiary care centre cohort., (The Author(s). Published by S. Karger AG, Basel.)

Pauci-immune focal necrotizing glomerulonephritis (piFNGN) involves asynchronous onset and progression of injurious lesions in biopsies. Pathologists can describe this heterogeneity within a biopsy, but translating the information into prognostic or expression analyses is challenging. Understanding the underlying molecular processes could improve treatment; however, bulk or single-cell transcriptomic analyses of dissociated tissue disregard the heterogeneity of glomerular injury. We characterize protein and mRNA expression of individual glomeruli in 20 biopsies from 18 patients with antineutrophil cytoplasmic antibody-associated piFNGN using the NanoString digital spatial profiling (DSP) platform. For this purpose, circular annotations of glomeruli were analyzed using protein, immuno-oncology RNA, and Cancer Transcriptome Atlas panels (n=120, 72, and 48 glomeruli, respectively). Histologic evaluation of glomerular patterns of injury was performed in adjacent serial sections. Expression data were processed by log2 transformation, quantile normalization, and batch adjustment. DSP revealed distinct but overlapping gene expression profiles relating to the morphological evolution of injurious lesions, including dynamic expression of various immune checkpoint regulators. Enrichment analysis indicated deregulated pathways that underline known and highlight novel potential mechanisms of disease. Moreover, by capturing individual glomeruli, DSP describes heterogeneity between and within biopsies. We demonstrate the benefit of spatial profiling for characterization of heterogeneous glomerular injury, indicating novel molecular correlates of glomerular injury in piFNGN., (Copyright © 2022 by the American Society of Nephrology.)