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
{"title":"MUC1突变导致常染色体显性小管间质肾病患者COVID-19死亡率增加8倍：一项观察性研究","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","doi":"10.1186/s12882-024-03896-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<sup>2</sup>) 1.1 (1.0-1.2), age (y) 1.04 (1.0-1.1).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9089,"journal":{"name":"BMC Nephrology","volume":"25 1","pages":"449"},"PeriodicalIF":2.2000,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654191/pdf/","citationCount":"0","resultStr":"{\"title\":\"Eight-fold increased COVID-19 mortality in autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations: an observational study.\",\"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\",\"doi\":\"10.1186/s12882-024-03896-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<sup>2</sup>) 1.1 (1.0-1.2), age (y) 1.04 (1.0-1.1).</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":9089,\"journal\":{\"name\":\"BMC Nephrology\",\"volume\":\"25 1\",\"pages\":\"449\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-12-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654191/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Nephrology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12882-024-03896-1\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Nephrology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12882-024-03896-1","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
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.
期刊介绍：
BMC Nephrology is an open access journal publishing original peer-reviewed research articles in all aspects of the prevention, diagnosis and management of kidney and associated disorders, as well as related molecular genetics, pathophysiology, and epidemiology.
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