METHODS: The National Health and Nutrition Examination Survey (NHANES) is a population-based observational study, conducted periodically in Mexican American, Other Hispanic, Non-Hispanic (NH) White, NH Black, and other racial/ethnic participants. We linked 2009-12 survey data of 8199 adults to the mortality data until 2019. By analyzing RNA gene sequences from oral rinse samples, microbiome alpha diversity within individuals was assessed using operational taxonomic unit (OTU) richness. Potential mediators included obesity, diabetes mellitus, dyslipidemia, hypertension, and periodontitis. Multivariable Cox proportional hazards regression and causal mediation analysis were used.
RESULTS: Baseline mean ± standard deviation (SD) age was 42.1 ± 15.1 years. Over a median follow-up of 9.1 years, 405 all-cause mortality occurred (CVD, 105; non-CVD, 300). Each 1-SD increment in OTU richness was inversely associated with all-cause mortality (hazard ratio [HR] 0.92, 95 % confidence interval [CI] 0.90-0.95), CVD mortality (HR, 0.92; 95 % CI, 0.90-0.95), and non-CVD mortality (HR, 0.92; 95 % CI, 0.90-0.95). With evidence of significant racial and ethnic groups-interaction (p <0.05), these associations were evident in Mexican American, NH White, and others racial/ethnic participants. None of the potential mediators significantly mediated the associations of OTU richness with all-cause, CVD, and non-CVD mortality.
CONCLUSIONS: Lower oral microbiome alpha diversity is associated with higher risk for all-cause, CVD, and non-CVD mortality, and the associations are varied by racial and ethnic groups.
METHODS: Patients with CBHA in 176 families were genetically examined using exome sequencing. Patients with disease-causing variants were clinically evaluated.
RESULTS: Disease-causing variants were identified in 96 of the 176 families (54.5%). After excluding 6 families, 48 patients from 42 families were categorized as having syndromic associations with CBHA, whereas the remaining 51 patients from 48 families had isolated CBHA. In 51 patients, 26 aberrant genes were identified, of which, 20 (76.9%) caused disease in 1 family each. The most prevalent genes were CACNA1A, ITPR1, and KIF1A. Of the 26 aberrant genes, 21 and 1 were functionally annotated to atrophy and hypoplasia, respectively. CBHA+S was more clinically severe than CBHA-S. Notably, ARG1 and FOLR1 variants were identified in 2 families, leading to medical treatments.
CONCLUSION: A wide genetic and clinical diversity of CBHA was revealed through exome sequencing in this cohort, which highlights the importance of comprehensive genetic analyses. Furthermore, molecular-based treatment was available for 2 families.
METHODS: Retrospective data were collected on 1148 children with biopsy-proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analysed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow-up.
RESULTS: The median follow-up was 3.7 years (interquartile range 2-6.2). At last follow-up, 29% of patients had an eGFR <90 mL/min/1.73 m2, 36% had proteinuria and 3% had chronic kidney disease stage 4-5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second-line immunosuppressive regimen being superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow-up.
CONCLUSION: In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly, there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN.