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Lookup NU author(s): Professor John SayerORCiD, Dr Holly Mabillard
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024.Background: MUC1 and UMOD pathogenic variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD). MUC1 is expressed in kidney, nasal mucosa and respiratory tract, while UMOD is expressed only in kidney. Due to haplo-insufficiency ADTKD-MUC1 patients produce approximately 50% of normal mucin-1. Methods: To determine whether decreased mucin-1 production was associated with an increased COVID-19 risk, we sent a survey to members of an ADTKD registry in September 2021, after the initial, severe wave of COVID-19. We linked results to previously obtained ADTKD genotype and plasma CA15-3 (mucin-1) levels and created a longitudinal registry of COVID-19 related deaths. Results: Surveys were emailed to 637 individuals, with responses from 89 ADTKD-MUC1 and 132 ADTKD-UMOD individuals. 19/83 (23%) ADTKD-MUC1 survey respondents reported a prior COVID-19 infection vs. 14/125 (11%) ADTKD-UMOD respondents (odds ratio (OR) 2.35 (95%CI 1.60–3.11, P = 0.0260). Including additional familial cases reported from survey respondents, 10/41 (24%) ADTKD-MUC1 individuals died of COVID-19 vs. 1/30 (3%) with ADTKD-UMOD, with OR 9.21 (95%CI 1.22–69.32), P = 0.03. The mean plasma mucin-1 level prior to infection in 14 infected and 27 uninfected ADTKD-MUC1 individuals was 7.06 ± 4.12 vs. 10.21 ± 4.02 U/mL (P = 0.035). Over three years duration, our longitudinal registry identified 19 COVID-19 deaths in 360 ADTKD-MUC1 individuals (5%) vs. 3 deaths in 478 ADTKD-UMOD individuals (0.6%) (P = 0.0007). Multivariate logistic regression revealed the following odds ratios (95% confidence interval) for COVID-19 deaths: ADTKD-MUC1 8.4 (2.9–29.5), kidney transplant 5.5 (1.6–9.1), body mass index (kg/m2) 1.1 (1.0-1.2), age (y) 1.04 (1.0-1.1). Conclusions: Individuals with ADTKD-MUC1 are at an eight-fold increased risk of COVID-19 mortality vs. ADTKD-UMOD individuals. Haplo-insufficient production of mucin-1 may be responsible.
Author(s): Kidd KO, Williams AH, Taylor A, Martin L, Robins V, Sayer JA, Olinger E, Mabillard HR, Papagregoriou G, Deltas C, Stavrou C, Conlon PJ, Hogan RE, Elhassan EAE, Springer D, Zima T, Izzi C, Vrbacka A, Piherova L, Pohludka M, Radina M, Vylet'al P, Hodanova K, Zivna M, Kmoch S, Bleyer AJ
Publication type: Article
Publication status: Published
Journal: BMC Nephrology
Year: 2024
Volume: 25
Issue: 1
Online publication date: 18/12/2024
Acceptance date: 27/11/2024
Date deposited: 08/01/2025
ISSN (electronic): 1471-2369
Publisher: BioMed Central Ltd
URL: https://doi.org/10.1186/s12882-024-03896-1
DOI: 10.1186/s12882-024-03896-1
Data Access Statement: The datasets generated and analysed during the current study are not publicly available to protect patient confdentiality. We are very happy to work with any groups interested in studying this condition and providing genetic information that can satisfy their research requests. An anonymized dataset analyzed in the study will be available from the European Genome-Phenome Archive (EGA-archive.org), with request of data access
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