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

BACKGROUND

and pathogenic variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD). is expressed in kidney, nasal mucosa and respiratory tract, while is expressed only in kidney. Due to haplo-insufficiency ADTKD- 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- and 132 ADTKD- individuals. 19/83 (23%) ADTKD- survey respondents reported a prior COVID-19 infection vs. 14/125 (11%) ADTKD- respondents (odds ratio (OR) 2.35 (95%CI 1.60-3.11, = 0.0260). Including additional familial cases reported from survey respondents, 10/41 (24%) ADTKD- individuals died of COVID-19 vs. 1/30 (3%) with ADTKD- , with OR 9.21 (95%CI 1.22-69.32), = 0.03. The mean plasma mucin-1 level prior to infection in 14 infected and 27 uninfected ADTKD- individuals was 7.06±4.12 vs. 10.21±4.02 U/mL ( = 0.035). Over three years duration, our longitudinal registry identified 19 COVID-19 deaths in 360 ADTKD- individuals (5%) vs. 3 deaths in 478 ADTKD- individuals (0.6%) ( = 0.0007). Multivariate logistic regression revealed the following odds ratios (95% confidence interval) for COVID-19 deaths: ADTKD- 8.4 (2.9-29.5), kidney transplant 5.5 (1.6-9.1), body mass index (kg/m ) 1.1 (1.0-1.2), age (y) 1.04 (1.0-1.1).

CONCLUSIONS

Individuals with ADTKD- are at an eight-fold increased risk of COVID-19 mortality vs. ADTKD- individuals. Haplo-insufficient production of mucin-1 may be responsible.