The effect of chronic hepatitis B virus (HBV) infection on the risk of chronic kidney disease (CKD) is controversial. We examined the prospective association between hepatitis B surface antigen (HBsAg) serology status and incident CKD in a large cohort of men and women. Cohort study of 299,913 adults free of CKD at baseline who underwent health screening exams between January 2002 and December 2016 in South Korea. Incident CKD was defined as the development of an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 and/or proteinuria. Over 1,673,701 person-years of follow-up, we observed 13,924 incident cases of CKD (3225 cases of eGFR < 60 ml/min/1.73m2 and 11,072 cases of proteinuria). In fully adjusted models comparing positive to negative HBsAg participants, the hazard ratio (HR, 95% confidence interval) for incident CKD was 1.11 (1.03–1.21; P = 0.01). The corresponding HR for incident proteinuria and for eGFR < 60 ml/min/1.73m2 were 1.23 (1.12–1.35; P < 0.001) and 0.89 (0.73–1.07; P = 0.21), respectively. The associations were similar across categories of liver enzyme levels at baseline. In this large cohort, HBsAg positive serology was associated with higher risk of incident CKD, and we provide novel evidence that this association was due to a higher incidence of proteinuria in HBsAg positive participants. Our study adds to the growing body of evidence suggesting that chronic HBV infection may be a contributor to the increasing incidence of CKD.

The role of alcohol consumption in the risk of vasomotor symptoms (VMS), the most cardinal climacteric symptoms, is not well established. We examined their relationship with early-onset VMS among premenopausal women. Moderately-to-severely bothersome VMS, the primary outcome, was assessed using the Korean version of the Menopause-Specific Quality of Life questionnaire. The alcohol consumption categories included lifetime abstainer, former drinker, or current drinker, categorized as light, moderate, heavy, and very heavy. Compared with the lifetime-abstinence (reference), the multivariable-adjusted odds ratio (95% CIs) for prevalent VMS in alcohol consumption of <10, 10–19, 20–39, and ≥40 g/day were 1.42 (1.02–1.99), 1.99 (1.27–3.12), 2.06 (1.19–3.57), and 3.52 (1.72–7.20), respectively (p trend <0.01). Compared with the lifetime-abstinence, the multivariable-adjusted hazard ratios (95% CIs) for incident bothersome VMS among average alcohol consumption of <10, 10–19, 20–39, and ≥40 g/day were 1.10 (0.85–1.41), 1.03 (0.70–1.51), 1.72 (1.06–2.78), and 2.22 (1.16–4.23), respectively (p trend = 0.02). Increased alcohol consumption positively and consistently showed a relationship with increased risk of both prevalent and incident early-onset VMS. Refraining from alcohol consumption may help prevent bothersome VMS in premenopausal women.

Somatically acquired mitochondrial DNA (mtDNA) mutations accumulate with age, but the mechanisms and consequences of this accumulation are poorly understood. Here we show that transient injuries induce a burst of persistent mtDNA mutations that impair resilience to future injuries. mtDNA mutations suppressed energy-intensive nucleotide metabolism. Repletion of adenosine, but not other nucleotides, restored adenosine triphosphate generation, which required a nuclear-encoded purine biosynthetic enzyme, adenylate kinase 4 (AK4). Analysis of 369,912 UK Biobank participants revealed a graded association between mutation burden and chronic kidney disease severity as well as an independent increase in the risk of future acute kidney injury events ( P < 10 ⁻⁷ ). Heteroplasmic mtDNA mutations may therefore reflect the cumulative effect of acute injuries to metabolically active cells, impairing major functions in a fashion amenable to nuclear-controlled purine biosynthesis.

Importance: With an increasing prevalence of diabetes mellitus (DM) and comorbid chronic kidney disease (CKD), health-related quality of life (HRQoL) in patients with DM and CKD needs to be better understood. Objective: To investigate the association between the severity of CKD on HRQoL in DM patients. Design: A cross-sectional study of a nationally representative population-based survey, the Korea National Health and Nutrition Examination Survey (KNHANES). Setting: Data collected between 2007 and 2018 from the KNHANES. Participants: Adult participants with DM who completed the self-administered European Quality of Life Questionnaire Five Dimension (EQ-5D) questionnaire (n = 7243). Exposures: CKD stages defined by the Kidney Disease Improving Global System (KDIGO) staging system. Main Outcomes and Measures: We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) of the presence of having problems in the 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) of EQ-5D by CKD stage after adjusting for socio-demographic parameters and comorbid conditions. In addition, the EQ-5D index, reflecting the overall health status, was compared across CKD stages. Results: Among 7243 participants (mean (standard error) age 58.2 (0.2) 56.9% male), 24.0% (n = 1768) had CKD and 8.6% (n = 775) had stage 3–5 CKD. Pain/discomfort was the most common problem (30.5%) among patients with DM. Participants with more advanced CKD were more likely to experience problems in all dimensions of EQ-5D except the anxiety/depression dimension. In particular, compared to those without CKD, the adjusted ORs (95% CI) for any problem in the usual activities dimension was 1.65 (1.30, 2.10) in CKD stage 3 and 4.23 (2.07, 8.67) in CKD stage 4–5. Moreover, participants with stage 3 (−0.016 (−0.029, −0.003)) and stage 4–5 CKD (−0.088 (−0.129, −0.048)) had significantly lower EQ-5D index than those without CKD. However, compared with no CKD, CKD stage 1–2 was not significantly associated with having any problem in any dimensions. Conclusions and Relevance: In this nationally representative study, patients with DM had a high prevalence of self-reported poor HRQoL and the prevalence increased with more advanced stages of CKD. Therefore, assessment of HRQoL and interventions are necessary at early stages of CKD in DM patients.

The role of nonalcoholic fatty liver disease (NAFLD) in vasomotor symptom (VMS) risk in premenopausal women is unknown. We examined the prevalence of early-onset VMSs according to NAFLD status in lean and overweight premenopausal women. This cross-sectional study included 4242 premenopausal Korean women (mean age 45.4 years). VMSs (hot flashes and night sweats) were assessed using the Korean version of the Menopause-Specific Quality of Life questionnaire. Hepatic steatosis was determined using liver ultrasound; lean was defined as a body mass index of <23 kg/m². Participants were categorized into four groups: NAFLD-free lean (reference), NAFLD-free overweight, lean NAFLD, and overweight NAFLD. Compared with the reference, the multivariable-adjusted prevalence ratios (PRs) (95% confidence intervals (CIs)) for VMSs in NAFLD-free overweight, lean NAFLD, and overweight NAFLD were 1.22 (1.06–1.41), 1.38 (1.06–1.79), and 1.49 (1.28–1.73), respectively. For moderate-to-severe VMSs, the multivariable-adjusted PRs (95% CIs) comparing NAFLD-free overweight, lean NAFLD, and overweight NAFLD to the reference were 1.38 (1.10–1.74), 1.73 (1.16–2.57), and 1.74 (1.37–2.21), respectively. NAFLD, even lean NAFLD, was significantly associated with an increased risk of prevalent early-onset VMSs and their severe forms among premenopausal women. Further studies are needed to determine the longitudinal association between NAFLD and VMS risk.