Eight-fold increased COVID-19 mortality in autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations: an observational study
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.
Funding
OP Integrated Infrastructure, the project: Research on COVID-19 progressive diagnostic methods and biomarkers useful in early detection of individuals at increased risk of severe disease, ITMS: 313011ATA2
European Regional Development Fund
Development of a System for Early and Rapid Detection, Identification, and Diagnosis of Novel Infectious Diseases with Pandemic Potential – COVID-19 Pilot Study
Slovak Research and Development Agency
Find out more...Identification and characterization of genetic factors contributing to inherited tubulointerstitial kidney disease II
Ministry of Health
Find out more...Prognostic factors affecting treatment outcomes and mortality in COVID-19 patients, new diagnostic methods, current and new terapeutic opportunities for COVID-19
Ministry of Health
Find out more...Advancing the diagnosis, understanding, and treatment of inherited kidney disease related to mucin-1 through improved family identification and new genetic, molecular, and biochemical approaches
Ministry of Education Youth and Sports
Find out more...Charles University in Prague (UNCE/MED/007)
Medical Research Council
Genetic Variation in Age of Onset of Kidney Failure in Uromodulin Kidney Disease
National Institute of Diabetes and Digestive and Kidney Diseases
Find out more...Chronic Kidney Disease (CKD) Biomarkers Consortium Data Coordinating Center
National Institute of Diabetes and Digestive and Kidney Diseases
Find out more...Slim Health Foundation
Black-Brogan Foundation
Soli Deo Gloria
Royal College of Surgeons in Ireland StAR PhD
History
Data Availability Statement
The datasets generated and analysed during the current study are not publicly available to protect patient confidentiality. 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.Comments
The original article is available at https://bmcnephrol.biomedcentral.com/Published Citation
Kidd KO, et al. Eight-fold increased COVID-19 mortality in autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations: an observational study. BMC Nephrol. 2024;25(1):449.Publication Date
18 December 2024External DOI
PubMed ID
39696072Department/Unit
- Beaumont Hospital
- Medicine
Publisher
BioMed CentralVersion
- Published Version (Version of Record)
