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Background Bone mineral density (BMD) predicts fracture risk in patients with chronic kidney disease (CKD) and in the general population. However, few studies have investigated risk factors for bone loss in patients with CKD. The aim of this study was to investigate whether renal function is associated with the rate of BMD decline. Methods A prospective cohort study included 1006 patients with CKD stages 2–4 between 2011 and 2016. BMD was measured using dual-energy X-ray absorptiometry at baseline and 4 years. The eGFR was measured 2–6 times during the 4-year follow-up. We analyzed the decline in bone mineral density according to CKD stage and further compared the rate of BMD decline according to eGFR trajectories at each stage. Results Advanced CKD stage was associated with a faster rate of decline in total hip BMD [stage 2 −0.23, stage 3A −0.39, stage 3B −0.80, stage 4 −1.23% change/year in men (P < .001); stage 2 −0.86, stage 3A −1.19, stage 3B −1.20, stage 4 −1.58% change/year in women (P  < .03)]. Two distinct eGFR trajectories (Class 1 stable group; Class 2 rapid decline group) were observed. The rapid decline group showed a trend toward an increased rate of decline in total hip BMD. Subgroup analysis according to eGFR trajectories revealed a significant difference in BMD decline rate between stable and rapid decline groups. Conclusions Advanced CKD stage and accelerated decline in renal function were associated with rapid BMD decline in non-dialysis patients with CKD. [ABSTRACT FROM AUTHOR]

Hair cortisol concentration (HCC) reflects the long‐term activity of the hypothalamus‐pituitary‐adrenal (HPA) axis in response to stress. Brain‐derived neurotrophic factor DNA methylation (BDNF DNAM) may affect HCC, and sex and Val66Met may contribute to this association. Thus, the aim of this study was to investigate the associations between HCC and Brain‐derived neurotrophic factor (BDNF) DNAM, and the moderating effects of Val66Met and sex. We recruited 191 healthy young participants (96 women, mean age 23.0 ± 2.6 years) and collected body samples to evaluate HCC, and to determine BDNF DNAM and Val66Met genotypes. We analyzed the effects of BDNF DNAM, sex, and Val66Met on HCC. We also evaluated the associations between BDNF DNAM and HCC in groups separated by sex and genotypes. We found a marked association of BDNF DNAM with HCC across men and women. After dividing the data by sex, a positive correlation of HCC with BDNF DNAM was found only in women. There was no substantial moderation effect of Val66Met genotypes on the association between BDNF DNAM and HCC. Therefore, BDNF DNAM was found to have positive association with HCC only in healthy young women, indicating that sex moderates the association of BDNF DNAM with long‐term HPA axis activity. [ABSTRACT FROM AUTHOR]

Optimal strategy for volume control and the clinical implication of achieved volume control are unknown in patients with sepsis-associated acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT). This randomized controlled trial aimed to compare the survival according to conventional or bioelectrical impedance analysis (BIA)-guided volume control strategy in patients with sepsis-associated AKI receiving CRRT. We also compared patient survival according to achieved volume accumulation rate ([cumulative fluid balance during 3 days × 100]/fluid overload measured by BIA at enrollment) as a post-hoc analysis. We randomly assigned patients to conventional volume control strategy (n = 39) or to BIA-guided volume control strategy (n = 34). There were no differences in 28-day mortality (HR, 1.19; 95% CI, 0.63–2.23) or 90-day mortality (HR, 0.99; 95% CI 0.57–1.75) between conventional and BIA-guided volume control group. In the secondary analysis, achieved volume accumulation rate was significantly associated with patient survival. Compared with the achieved volume accumulation rate of ≤ − 50%, the HRs (95% CIs) for the risk of 90-day mortality were 1.21 (0.29–5.01), 0.55 (0.12–2.48), and 7.18 (1.58–32.51) in that of − 50–0%, 1–50%, and > 50%, respectively. Hence, BIA-guided volume control in patients with sepsis-associated AKI receiving CRRT did not improve patient outcomes. In the secondary analysis, achieved volume accumulation rate was associated with patient survival. [ABSTRACT FROM AUTHOR]

Background Insomnia is a known risk factor for cardio-cerebrovascular disease in the general population; however, its effect on cardio-cerebrovascular outcomes in end-stage kidney disease patients is unclear. Therefore, this study aimed to investigate the association between cardio-cerebrovascular outcomes and insomnia in patients who initiated maintenance dialysis. Methods This study used nationwide Korean health insurance claims data to analyze 79   420 patients who initiated maintenance dialysis from January 2009 to December 2017. Insomnia was defined using claim codes and sleep medication prescription data. Patients were categorized according to the presence of insomnia before and after dialysis initiation: (i) no insomnia, (ii) insomnia before dialysis only (improved insomnia), (iii) insomnia after dialysis only (developed insomnia) and (iv) insomnia in both periods (persistent insomnia). The primary and secondary outcomes were major adverse cardiac and cerebrovascular events (MACCE) and all-cause mortality, respectively. The outcome risks were estimated by Cox regression models with inverse probability of treatment weighting. Results The mean age was 61.4 ± 13.4 years, and 39.7% were women. During the transition period from pre-dialysis to maintenance dialysis, 13.2% experienced insomnia. The insomnia groups showed significantly higher risks for MACCE [weighted hazard ratios (95% confidence intervals): developed insomnia, 1.26 (1.25–1.28); improved insomnia, 1.31 (1.29–1.33); persistent insomnia, 1.39 (1.37–1.41)] and higher all-cause mortality risks than the no insomnia group. The insomnia-related cardio-cerebrovascular disease risk elevation was more prominent in younger and male patients. Conclusions Insomnia may increase cardio-cerebrovascular disease and all-cause mortality risk among end-stage kidney disease patients who initiate maintenance dialysis. [ABSTRACT FROM AUTHOR]

Objectives To investigate the association between periodontal disease and the development of inflammatory arthritides in the general population. Methods In total, 489 125 participants from the UK Biobank without a previous history of RA, AS and PsA were enrolled. The primary outcome was the incidence of inflammatory arthritides, which was a composite of RA, AS and PsA according to the presence of periodontal disease based on self-reported oral health indicators. Multivariate Cox proportional hazard regression analyses using four different models were performed to assess the association between periodontal disease and inflammatory arthritides development. Results In all, 86 905 and 402 220 individuals were categorized as with and without periodontal disease, respectively. Cox hazard analysis indicated that the presence of periodontal disease was an independent predictor of the occurrence of composite outcomes of inflammatory arthritides, which was also consistent for RA and AS. Significant associations were found to be consistent in the four Cox models and were replicated even when different criteria were used to define periodontal disease. Subgroup analyses indicated that periodontal disease was associated with an increased RA risk in those aged <60 years, and this risk was persistent for both male and female patients and for patients with seropositive/seronegative RA. Conclusion Self-reported periodontal disease is associated with inflammatory arthritides incidence in participants included in the UK Biobank, particularly for RA and AS. Higher clinical attention and optimal dental care in patients with signs of periodontal disease may be recommended for early disease detection and for reducing this risk. [ABSTRACT FROM AUTHOR]

Background Although albuminuria is the gold standard for defining chronic kidney disease (CKD), total proteinuria has also been widely used in real-world clinical practice. Moreover, the superiority of the prognostic performance of albuminuria over proteinuria in patients with CKD remains inconclusive. Therefore, we aimed to compare the predictive performances of albuminuria and proteinuria in these patients. Methods From the Korean Cohort Study for Outcome in Patients with CKD we included 2099 patients diagnosed with CKD grades 1–5 who did not require kidney replacement therapy. We measured the spot urine albumin:creatinine ratio (mACR) and protein:creatinine ratio (PCR) and estimated the ACR (eACR) using the PCR. Kidney failure risk equation (KFRE) scores were calculated using the mACR, PCR and eACR. The primary outcome was the 5-year risk of kidney failure with replacement therapy (KFRT). Results The eACR significantly underestimated mACR in patients with low albuminuria levels. The time-dependent area under the receiver operating characteristics curve showed excellent predictive performance for all KFRE scores from the mACR, PCR and eACR. However, eACR was inferior to mACR based on the continuous net reclassification index (cNRI) and integrated discrimination improvement index (IDI) in all CKD cause groups, except for the group with an unclassified aetiology. Moreover, the cNRI and IDI statistics indicated that both eACR and PCR were inferior to mACR in patients with low albuminuria (<30 mg/g). Conversely, the predictive performance of PCR was superior in severe albuminuria and nephrotic-range proteinuria, in which the IDI and cNRI of the PCR were greater than those of the mACR. Conclusions The mACR, eACR and PCR showed excellent performance in predicting KFRT in patients with CKD. However, eACR was inferior to mACR in patients with low albuminuria, indicating that measuring rather than estimating albuminuria is preferred for these patients. [ABSTRACT FROM AUTHOR]

Purpose: Recent advances have led to greater recognition of the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD). There has been evidence that CKD is also associated with dysbiosis. Here, we aimed to evaluate whether probiotic supplements can have protective effects against kidney injury via improving mitochondrial function.An animal model of CKD was induced by feeding C57BL/6 mice a diet containing 0.2% adenine. KBL409, a strain of Lactobacillus acidophilus, was administered via oral gavage at a dose of 1 × 109 CFU daily. To clarify the underlying mechanisms by which probiotics exert protective effects on mitochondria in CKD, primary mouse tubular epithelial cells stimulated with TGF-β and p-cresyl sulfate were administered with butyrate.In CKD mice, PGC-1α and AMPK, key mitochondrial energy metabolism regulators, were down-regulated. In addition, mitochondrial dynamics shifted toward fission, the number of fragmented cristae increased, and mitochondrial mass decreased. These alterations were restored by KBL409 administration. KBL409 supplementation also improved defects in fatty acid oxidation and glycolysis and restored the suppressed enzyme levels involved in TCA cycle. Accordingly, there was a concomitant improvement in mitochondrial respiration and ATP production assessed by mitochondrial function assay. These favorable effects of KBL409 on mitochondria ultimately decreased kidney fibrosis in CKD mice. In vitro analyses with butyrate recapitulated the findings of animal study.This study demonstrates that administration of the probiotic Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function.Methods: Recent advances have led to greater recognition of the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD). There has been evidence that CKD is also associated with dysbiosis. Here, we aimed to evaluate whether probiotic supplements can have protective effects against kidney injury via improving mitochondrial function.An animal model of CKD was induced by feeding C57BL/6 mice a diet containing 0.2% adenine. KBL409, a strain of Lactobacillus acidophilus, was administered via oral gavage at a dose of 1 × 109 CFU daily. To clarify the underlying mechanisms by which probiotics exert protective effects on mitochondria in CKD, primary mouse tubular epithelial cells stimulated with TGF-β and p-cresyl sulfate were administered with butyrate.In CKD mice, PGC-1α and AMPK, key mitochondrial energy metabolism regulators, were down-regulated. In addition, mitochondrial dynamics shifted toward fission, the number of fragmented cristae increased, and mitochondrial mass decreased. These alterations were restored by KBL409 administration. KBL409 supplementation also improved defects in fatty acid oxidation and glycolysis and restored the suppressed enzyme levels involved in TCA cycle. Accordingly, there was a concomitant improvement in mitochondrial respiration and ATP production assessed by mitochondrial function assay. These favorable effects of KBL409 on mitochondria ultimately decreased kidney fibrosis in CKD mice. In vitro analyses with butyrate recapitulated the findings of animal study.This study demonstrates that administration of the probiotic Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function.Results: Recent advances have led to greater recognition of the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD). There has been evidence that CKD is also associated with dysbiosis. Here, we aimed to evaluate whether probiotic supplements can have protective effects against kidney injury via improving mitochondrial function.An animal model of CKD was induced by feeding C57BL/6 mice a diet containing 0.2% adenine. KBL409, a strain of Lactobacillus acidophilus, was administered via oral gavage at a dose of 1 × 109 CFU daily. To clarify the underlying mechanisms by which probiotics exert protective effects on mitochondria in CKD, primary mouse tubular epithelial cells stimulated with TGF-β and p-cresyl sulfate were administered with butyrate.In CKD mice, PGC-1α and AMPK, key mitochondrial energy metabolism regulators, were down-regulated. In addition, mitochondrial dynamics shifted toward fission, the number of fragmented cristae increased, and mitochondrial mass decreased. These alterations were restored by KBL409 administration. KBL409 supplementation also improved defects in fatty acid oxidation and glycolysis and restored the suppressed enzyme levels involved in TCA cycle. Accordingly, there was a concomitant improvement in mitochondrial respiration and ATP production assessed by mitochondrial function assay. These favorable effects of KBL409 on mitochondria ultimately decreased kidney fibrosis in CKD mice. In vitro analyses with butyrate recapitulated the findings of animal study.This study demonstrates that administration of the probiotic Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function.Conclusions: Recent advances have led to greater recognition of the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD). There has been evidence that CKD is also associated with dysbiosis. Here, we aimed to evaluate whether probiotic supplements can have protective effects against kidney injury via improving mitochondrial function.An animal model of CKD was induced by feeding C57BL/6 mice a diet containing 0.2% adenine. KBL409, a strain of Lactobacillus acidophilus, was administered via oral gavage at a dose of 1 × 109 CFU daily. To clarify the underlying mechanisms by which probiotics exert protective effects on mitochondria in CKD, primary mouse tubular epithelial cells stimulated with TGF-β and p-cresyl sulfate were administered with butyrate.In CKD mice, PGC-1α and AMPK, key mitochondrial energy metabolism regulators, were down-regulated. In addition, mitochondrial dynamics shifted toward fission, the number of fragmented cristae increased, and mitochondrial mass decreased. These alterations were restored by KBL409 administration. KBL409 supplementation also improved defects in fatty acid oxidation and glycolysis and restored the suppressed enzyme levels involved in TCA cycle. Accordingly, there was a concomitant improvement in mitochondrial respiration and ATP production assessed by mitochondrial function assay. These favorable effects of KBL409 on mitochondria ultimately decreased kidney fibrosis in CKD mice. In vitro analyses with butyrate recapitulated the findings of animal study.This study demonstrates that administration of the probiotic Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function. [ABSTRACT FROM AUTHOR]

The association of overweight/obesity and metabolically unhealthy (MU) with the risk of developing Barrett's esophagus (BE) remains uncertain. We evaluated whether MU and overweight/obesity are associated with increased BE incidence and whether they have a synergistic impact on BE development. We analyzed the body mass index (BMI) and metabolic indicators at baseline of 402,510 individuals from the UK Biobank with no history of BE. Overweight/obesity and MU were defined as BMI ≥ 25.0 kg/m 2 and presence of ≥ 1 MU indicators, respectively. Accordingly, the participants were categorized into four groups: (1) metabolically healthy non-overweight/obesity (MHNO), (2) metabolically unhealthy non-overweight/obesity (MUNO), (3) metabolically healthy overweight/obesity (MHO), and (4) metabolically unhealthy overweight/obesity (MUO). During a median follow-up of 13.5 years, 6195 (1.5%) individuals were newly diagnosed with BE. Among them, 39,281 (9.8%), 92,000 (22.9%), 25,297 (6.3%), and 245,932 (61.1%) individuals were classified as MHNO, MUNO, MHO, and MUO, respectively. In Cox regression analyses, both MU and overweight/obesity were independently associated with BE incidence. Moreover, BE incidence was significantly higher in the MUNO, MHO, and MUO groups, compared to the MHNO group. MU and overweight/obesity are independent risk factors for BE and have a synergistic effect on BE development., (© 2024. The Author(s).)

Hair cortisol concentration (HCC) reflects the long-term activity of the hypothalamus-pituitary-adrenal (HPA) axis in response to stress. Brain-derived neurotrophic factor DNA methylation (BDNF DNA M ) may affect HCC, and sex and Val66Met may contribute to this association. Thus, the aim of this study was to investigate the associations between HCC and Brain-derived neurotrophic factor (BDNF) DNA M , and the moderating effects of Val66Met and sex. We recruited 191 healthy young participants (96 women, mean age 23.0 ± 2.6 years) and collected body samples to evaluate HCC, and to determine BDNF DNA M and Val66Met genotypes. We analyzed the effects of BDNF DNA M , sex, and Val66Met on HCC. We also evaluated the associations between BDNF DNA M and HCC in groups separated by sex and genotypes. We found a marked association of BDNF DNA M with HCC across men and women. After dividing the data by sex, a positive correlation of HCC with BDNF DNA M was found only in women. There was no substantial moderation effect of Val66Met genotypes on the association between BDNF DNA M and HCC. Therefore, BDNF DNA M was found to have positive association with HCC only in healthy young women, indicating that sex moderates the association of BDNF DNA M with long-term HPA axis activity., (© 2024 The Authors. Stress and Health published by John Wiley & Sons Ltd.)

Background: Atrial fibrillation (AF) can lead to stroke, heart failure, and mortality and has a greater prevalence in dialysis patients than in the general population. Several studies have suggested that uremic toxins may contribute to the development of AF. However, the association between dialysis adequacy and incident AF has not been well established., Methods: In this retrospective nationwide cohort study, we analyzed data from the Korean National Periodic Hemodialysis Quality Assessment from 2013 to 2015 of patients who received outpatient maintenance hemodialysis 3× a week. The main exposure was single pooled Kt/V (spKt/V), which is the dialysis adequacy index, and the primary outcome was the development of AF. For the primary analysis, patients were categorized into quartiles according to baseline spKt/V. The lowest quartile, representing the lowest adequacy, was used as the reference group. Fine-Gray subdistribution hazard models were used, treating all-cause mortality as a competing risk., Results: Of 25 173 patients, the mean age was 60 (51-69) years, and 14 772 (58.7%) were men. During a median follow-up of 5.7 years, incident AF occurred in a total of 3883 (15.4%) patients. Participants with a higher spKt/V tended to have lower AF incidence. In survival analysis, a graded association was observed between the risk of incident AF and spKt/V quartiles: subdistribution hazard ratios and 95% CIs for the second, third, and the highest quartile compared with the lowest quartile were 0.90 (95% CI, 0.82-0.98), 0.84 (95% CI, 0.77-0.93), and 0.79 (95% CI, 0.72-0.88), respectively., Conclusions: This nationwide cohort study showed that a higher spKt/V is associated with a reduced risk of incident AF. These findings suggests that reducing uremic toxin burden through enhanced dialysis clearance may be associated with a lower risk of AF development in patients undergoing maintenance hemodialysis., Competing Interests: None.

Background: Coronary artery calcification (CAC) is highly prevalent in patients with chronic kidney disease (CKD) and is associated with major adverse cardiovascular events and metabolic disturbances. The triglyceride-glucose index (TyGI), a novel surrogate marker of metabolic syndrome and insulin resistance, is associated with CAC in the general population and in patients with diabetes. This study investigated the association between the TyGI and CAC progression in patients with CKD, which is unknown., Methods: A total of 1,154 patients with CKD (grades 1-5; age, 52.8 ± 11.9 years; male, 688 [59.6%]) were enrolled from the KNOWCKD (KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease). The TyGI was calculated as follows: ln (fasting triglycerides × fasting glucose/2). Patients were classified into tertiles (low, intermediate, high) based on the TyGI. The primary outcome was annualized percentage change in CAC score [(percent change in CAC score + 1)12/follow-up months - 1] of ≥15%, defined as CAC progression., Results: During the 4-year follow-up, the percentage of patients with CAC progression increased across TyGI groups (28.6%, 37.5%, and 46.2% in low, intermediate, and high groups, respectively; p < 0.001). A high TyGI was associated with an increased risk of CAC progression (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.14-3.88; p = 0.02) compared to the low group. Moreover, a 1-point increase in the TyGI was related to increased risk of CAC progression (OR, 1.55; 95% CI, 1.06-1.76; p = 0.02) after adjustment., Conclusion: A high TyGI may be a useful predictor of CAC progression in CKD.

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficient activity of α-galactosidase (α-Gal A), affecting multiple organs including kidney. In this study, we aimed to determine the prevalence of FD in patients with chronic kidney disease (CKD) including those on renal replacement therapy in Korea., Methods: This is a national, multicenter, observational study performed between August 24, 2017 and February 28, 2020. Patients with the presence of proteinuria or treated on dialysis were screened by measuring the α-Gal A enzyme activity using either dried blood spot or whole blood, and plasma globotriaosylsphingosine (lyso-GL3) concentration. A GLA gene analysis was performed in patients with low α-Gal A enzyme activity or increased plasma lyso-GL3 concentration., Results: Of 897 screened patients, 405 (45.2%) were male and 279 (31.1%) were on dialysis. The α-Gal A enzyme activity was measured in 891 patients (99.3%), and plasma lyso-GL3 concentration was measured in all patients. Ten patients were eligible for a GLA gene analysis: eight with low α-Gal A enzyme activity and two with increased plasma lyso-GL3 concentration. The GLA mutations were analyzed in nine patients and one patient was found with a pathogenic mutation. Therefore, one patient was identified with FD, giving a prevalence of 0.1% (1 of 897) in this CKD population., Conclusion: Although the prevalence of FD in the CKD population was low (0.1%), screening tests are crucial to detect potential diseases in patients with relatives who can benefit from early treatment.

Background: Fluid overload is an independent risk factor of mortality in patients with acute kidney injury (AKI) receiving continuous kidney replacement therapy (CKRT). However, the association between fluid status, as assessed by bioelectrical impedance analysis (BIA) or lung ultrasound, and survival in patients with AKI requiring CKRT has not been established., Methods: We analyzed 36 participants with sepsis-associated AKI who received CKRT at a tertiary hospital. The main exposures were volume surrogates: 1) overhydration normalized by extracellular water (OH/ECW, L/L) assessed by BIA, 2) the number of B-lines measured by lung ultrasound, and 3) weight change ([body weight at CKRT initiation - body weight at admission] × 100/body weight at admission). The primary outcome was the 28-day mortality., Results: Seventeen participants (47.2%) died within 28 days. There were no significant correlations between OH/ECW and weight change (R2 = 0.040, p = 0.24), number of B-lines and OH/ECW (R2 = 0.056, p = 0.16), or weight change and number of B-lines (R2 = 0.014, p = 0.49). Kaplan-Meier analyses revealed that patients in the highest tertile of OH/ECW showed a significantly lower cumulative 28-day survival probability than the others (the lowest + middle tertiles). The survival probability of participants in the highest tertile of the number of B-lines or weight change did not differ from that of their counterparts. In a multivariate Cox proportional hazard model, the hazard ratio for the highest tertile of OH/ECW was 3.83 (95% confidence interval, 1.04-14.03)., Conclusion: Volume overload assessed using BIA (OH/ECW) was associated with the 28-day survival rate in patients with sepsis-associated AKI who received CKRT.