Eight-Fold Increased COVID-19 Mortality in Autosomal Dominant Tubulointerstitial Kidney Disease due to MUC1 Mutations: An Observational Study-Reference-Cited by-同舟云学术

Eight-Fold Increased COVID-19 Mortality in Autosomal Dominant Tubulointerstitial Kidney Disease due to MUC1 Mutations: An Observational Study

Published:2024-09-03 Issue: Volume: Page:
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Author:

Kidd Kendrah O.¹,Williams Adrienne H.²,Taylor Abbigail¹,Martin Lauren¹,Robins Victoria¹,Sayer John A.³,Olinger Eric⁴,Mabillard Holly R.³,Papagregoriou Gregory⁵,Deltas Constantinos⁵,Stavrou Christoforos⁶,Conlon Peter J.⁷,Hogan Richard Edmund⁷,Elhassan Elhussein A.E.⁷,Springer Drahomíra⁸,Zima Tomáš⁸,Izzi Claudia⁹,Vrbacká Alena¹⁰,Piherová Lenka¹⁰,Pohludka Michal¹¹,Radina Martin¹⁰,Vylet’al Petr¹⁰,Hodanova Katerina¹⁰,Zivna Martina¹⁰,Kmoch Stanislav¹⁰,Bleyer Anthony J.¹

Affiliation:

1. Wake Forest University School of Medicine Medical Center Blvd

2. DNA Data Solutions, LLC

3. Newcastle University

4. Cliniques universitaires Saint-Luc

5. University of Cyprus

6. Evangelismos Hospital

7. Royal College of Surgeons in Ireland

8. General University Hospital and the First Faculty of Medicine of Charles University

9. Spedali Civili di Brescia

10. Charles University

11. GeneSpector

Abstract

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.

Publisher

Springer Science and Business Media LLC

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