Eight-fold increased COVID-19 mortality in autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations: an observational study
Year: 2024
Type: article
Study design: Observational Study
Abstract: 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/m 2 ) 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.
Source: BMC Nephrology
Authors: Kendrah O. Kidd, Adrienne H. Williams, Abbigail Taylor, Lauren Martin, Victoria Robins, John A. Sayer, Eric Olinger, Holly R. Mabillard, Gregory Papagregoriou, Constantinos Deltas, Christoforos Stavrou, Peter J. Conlon, Richard Edmund Hogan, Elhussein A.E. Elhassan, Drahomíra Springer, Tomáš Zima, Claudia Izzi, Alena Vrbacká, Lenka Piherová, Michal Pohludka, Martin Radina, Petr Vylet’al, Katerina Hodanova, Martina Zivna, Stanislav Kmoch, Anthony J. Bleyer
Institutions: Charles University, Wake Forest University Health Sciences, Wake Forest University, Atrium Health Wake Forest Baptist, Newcastle upon Tyne Hospitals NHS Foundation Trust, NIHR Newcastle Biomedical Research Centre, Newcastle University, Cliniques Universitaires Saint-Luc, University of Cyprus, Royal College of Surgeons in Ireland, Beaumont Hospital, General University Hospital in Prague, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, University of Brescia, Medirex Group Academy
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,890
Funders: Univerzita Karlova v Praze, Royal College of Surgeons in Ireland, University of Cyprus, Royal College of Surgeons of England, European Commission, Ministerstvo Zdravotnictví Ceské Republiky, Agentúra na Podporu Výskumu a Vývoja, National Institutes of Health, Medical Research Council, European Regional Development Fund, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1170812628, Biobanking and the Cyprus Human Genome Project, Chronic Kidney Disease (CKD) Biomarkers Consortium Data Coordinating Center, G2662683434, G2761356519, G2972156800, G350361035, G434337789, Vytvorenie systému skorej a rýchlej detekcie, identifikácie a diagnostiky nových infekčných ochorení s pandemickým potenciálom – pilotná štúdia COVID-19, G5514976981, G6122222817, G682720903, G8415457339, G8427157459, G849167750, G9000194973
OpenAlex ID: W4405546004