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T lymphocytes modulate early ischemia-reperfusion injury in the kidney; however, their role during repair is unknown. We studied the role of TCRbeta(+)CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), known to blunt immune responses, in repair after ischemia-reperfusion injury to the kidney. Using a murine model of ischemic acute kidney injury we found that there was a significant trafficking of Tregs into the kidneys after 3 and 10 days. Post-ischemic kidneys had increased numbers of TCRbeta(+)CD4(+) and TCRbeta(+)CD8(+) T cells with enhanced pro-inflammatory cytokine production. Treg depletion starting 1 day after ischemic injury using anti-CD25 antibodies increased renal tubular damage, reduced tubular proliferation at both time points, enhanced infiltrating T lymphocyte cytokine production at 3 days and TNF-alpha generation by TCRbeta(+)CD4(+) T cells at 10 days. In separate mice, infusion of CD4(+)CD25(+) Tregs 1 day after initial injury reduced INF-gamma production by TCRbeta(+)CD4(+) T cells at 3 days, improved repair and reduced cytokine generation at 10 days. Treg manipulation had minimal effect on neutrophil and macrophage infiltration; Treg depletion worsened mortality and serum creatinine, while Treg infusion had a late beneficial effect on serum creatinine in bilateral ischemia. Our study demonstrates that Tregs infiltrate ischemic-reperfused kidneys during the healing process promoting repair, likely through modulation of pro-inflammatory cytokine production of other T cell subsets. Treg targeting could be a novel therapeutic approach to enhance recovery from ischemic acute kidney injury. [ABSTRACT FROM AUTHOR]

Soft robots have partially or entirely provided versatile opportunities for issues or roles that cannot be addressed by conventional machine robots, although most studies are limited to designs, controls, or physical/mechanical motions. Here, we present a transformable, reconfigurable robotic platform created by the integration of magnetically responsive soft composite matrices with deformable multifunctional electronics. Magnetic compounds engineered to undergo phase transition at a low temperature can readily achieve reversible magnetization and conduct various changes of motions and shapes. Thin and flexible electronic system designed with mechanical dynamics does not interfere with movements of the soft electronic robot, and the performances of wireless circuit, sensors, and devices are independent of a variety of activities, all of which are verified by theoretical studies. Demonstration of navigations and electronic operations in an artificial track highlights the potential of the integrated soft robot for on-demand, environments-responsive movements/metamorphoses, and optoelectrical detection and stimulation. Further improvements to a miniaturized, sophisticated system with material options enable in situ monitoring and treatment in envisioned areas such as biomedical implants., Competing Interests: Declarations. Conflict of Interest: The authors declare no interest conflict. They have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025. The Author(s).)

Background : Uric acid levels are linked to cardiovascular outcomes and mortality, especially in chronic kidney disease (CKD). However, their impact across varying kidney function remains unclear. Methods : We conducted a retrospective cohort study using the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) database from a single center. Adult patients with at least one serum uric acid measurement between 2002 and 2021 were included and categorized by estimated glomerular filtration rate (eGFR): normal kidney function (≥90 mL/min/1.73 m 2 ), mild dysfunction (60-89 mL/min/1.73 m 2 ), moderate dysfunction (30-59 mL/min/1.73 m 2 ), and advanced dysfunction (<30 mL/min/1.73 m 2 ). The primary outcome was all-cause mortality with secondary outcomes being myocardial infarction (MI) and heart failure (HF). Results : A total of 242,793 participants were analyzed. Uric acid levels showed a U-shaped association with all-cause mortality in advanced kidney dysfunction, where both low (<3 mg/dL) and high (>10 mg/dL) levels increased mortality risk. In mild kidney dysfunction, lower uric acid levels were linked to better survival. HF risk increased linearly with higher uric acid, particularly in normal kidney function, while no significant association was found between uric acid and MI in any group. Conclusions : Uric acid levels are associated with mortality in a U-shaped pattern for advanced kidney dysfunction, while lower levels appear protective in mild dysfunction. These findings suggest the need for personalized uric acid management in CKD patients based on their kidney function.

Background: Chronic kidney disease (CKD) patients face critical decisions in choosing kidney replacement therapy such as hemodialysis (HD) or peritoneal dialysis (PD), which significantly affect their quality of life and health outcomes. Recent studies highlight the importance of shared decision-making (SDM) in helping patients understand their treatment options and make informed choices. SDM not only improves patient satisfaction and autonomy but also emphasizes the need for comprehensive pre-dialysis education to support optimal treatment selection., Methods: Among patients with chronic kidney failure from 8 hospitals in Korea who started dialysis, 256 who participated in a pilot project for home management of PD were included in the present study. A mixed-methods study was conducted using questionnaires and semi-structured interviews. Our study focused on the effects of SDM on patient death, survival rate, HD conversion, emergency room visits, hospitalization days, and outpatient visits., Results: A significant difference was observed in hospitalization days (P = .0044) between the SDM and non-SDM groups. However, no significant differences were observed in survival rate, rate of conversion to HD, survival rate after conversion to HD, emergency room visit rate, number of hospitalizations per patient, outpatient visit rate, medical cost, hospitalization cost, outpatient cost, and phosphate-binding agent prescription rate., Conclusions: This study emphasizes the benefits of SDM in reducing hospitalization days for PD patients, suggesting its potential role as a guide in future decisions regarding PD. PD provides a particularly beneficial home-based treatment alternative for patients facing challenges with hospital visits, supported by advanced technologies. Overseas, various countries are implementing policies and incentives to promote home dialysis, demonstrating the potential for SDM to enhance patient satisfaction and outcomes in dialysis care globally., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Acute kidney injury (AKI) may transition into acute kidney disease (AKD) or chronic kidney disease (CKD), leading to subacute and chronic deterioration, respectively. Despite extensive research on AKI, a significant gap exists in understanding the specific biomarkers and development of individualized treatments prior to progression to AKD and CKD., Methods: As a consortium linking health medical records, biospecimens, and biosignals, eight Korean tertiary hospitals participated in the establishment of a retrospective and prospective cohort, each comprising approximately 1,500 patients with AKI receiving continuous kidney replacement therapy (CKRT). Other information included AKI-related information, CKRT prescriptions, and patient outcomes. Follow-up timeframes were set at baseline, 1 week, 3 months, and 1 year after the initiation of CKRT. Human biospecimens will be collected from the prospective cohort. An artificial intelligence model was developed using the retrospective cohort to predict the prognosis of AKD and its subsequent sequelae and to formulate patient-individualized treatments, with validation planned in a prospective cohort. Follow-up studies are scheduled to identify biomarkers related to outcomes using biospecimens. Finally, based on the results and literature review, decision-making on the prevention and management of diseases, as well as the development of treatment guidelines, are being planned., Conclusion: This study will provide scientific evidence on clinical insights and appropriate management targets for AKI and AKD, which will form the basis for relevant treatment guidelines. Additionally, these findings may facilitate a more personalized approach to patient care, enabling clinicians to tailor treatments based on individual biomarker profiles and predictive models.

As the regenerative mechanisms of biological organisms, self-healing provides useful functions for soft electronics or associated systems. However, there have been few examples of soft electronics where all components have self-healing properties while also ensuring compatibility between components to achieve multifunctional and resilient bio-integrated electronics. Here, we introduce a stretchable, biodegradable, self-healing conductor constructed by combination of two layers: (i) synthetic self-healing elastomer and (ii) self-healing conductive composite with additives. Abundant dynamic disulfide and hydrogen bonds of the elastomer and conductive composite enable rapid and complete recovery of electrical conductivity (~1000 siemens per centimeter) and stretchability (~500%) in response to repetitive damages, and chemical interactions of interpenetrated polymer chains of these components facilitate robust adhesion strength, even under extreme mechanical stress. System-level demonstration of soft, self-healing electronics with diagnostic/therapeutic functions for the urinary bladder validates the possibility for versatile, practical uses in biomedical research areas.

Background: Glycemic control is crucial in peritoneal dialysis (PD) patients with diabetes. Although fasting blood glucose (FBG) is the most commonly used index to measure blood glucose levels, there is currently no evidence supporting the association between FBG level and mortality risk in PD patients., Methods: A total of 3548 diabetic PD patients between 2002 and 2018 were enrolled from the National Health Insurance Service database of Korea. We investigated the association between FBG levels and the risk of all-cause and cause-specific mortality., Results: Patients with FBG levels 80-99 mg/dL exhibited the highest survival rates, whereas those with FBG levels ≥180 mg/dL had the lowest survival rates. Compared with FBG levels 80-99 mg/dL, the adjusted hazard ratios and 95% confidence interval for all-cause mortality significantly increased as follows: 1.02 (0.87-1.21), 1.41 (1.17-1.70), 1.44 (1.18-2.75), and 2.05 (1.73-2.42) for patients with FBG 100-124 mg/dL, FBG 125-149 mg/dL, FBG 150-179 mg/dL, and FBG ≥180 mg/dL, respectively. The risk for all-cause mortality also showed an increasing pattern in patients with FBG levels <80 mg/L. The risk of cardiovascular death significantly increased as FBG levels exceeded 125 mg/dL. However, the risk of infection-related and malignancy-related deaths did not show a significant increase with increasing FBG levels., Conclusion: There was an increase in the risk of all-cause mortality as FBG levels exceeded 125 mg/dL in PD patients with diabetes, and the risk of cardiovascular death showed a strong correlation with FBG levels compared with other causes of death., (© 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Glycemic control is particularly important in hemodialysis (HD) patients with diabetes mellitus (DM). Although fasting blood glucose (FBG) level is an important indicator of glycemic control, a clear target for reducing mortality in HD patients with DM is lacking., Methods: A total of 26,162 maintenance HD patients with DM were recruited from the National Health Insurance Database of Korea between 2002 and 2018. We analyzed the association of FBG levels at the baseline health examination with the risk of all-cause and cause-specific mortality., Results: Patients with FBG 80-100 mg/dL showed a higher survival rate compared with that of other FBG categories (p < 0.001). The risk of all-cause mortality increased with the increase in FBG levels, and adjusted hazard ratios (HRs) were 1.10 (95% confidence interval [CI], 1.04-1.17), 1.21 (95% CI, 1.13-1.29), 1.36 (95% CI, 1.26-1.46), and 1.61 (95% CI, 1.51-1.72) for patients with FBG 100-125, 125-150, 150-180, and ≥180 mg/dL, respectively. The HR for mortality was also significantly increased in patients with FBG <80 mg/dL (adjusted HR, 1.14; 95% CI, 1.05-1.23). The analysis of cause-specific mortality also revealed a J-shaped curve between FBG levels and the risk of cardiovascular deaths. However, the risk of infection or malignancy-related deaths was not linearly increased as FBG levels increased., Conclusion: A J-shaped association was observed between FBG levels and the risk of all-cause mortality, with the lowest risk at FBG 80-100 mg/dL in HD patients with DM.

Materials that have the ability to manipulate shapes in response to stimuli such as heat, light, humidity and magnetism offer a means for versatile, sophisticated functions in soft robotics or biomedical implants, while such a reactive transformation has certain drawbacks including high operating temperatures, inherent rigidity and biological hazard. Herein, we introduce biodegradable, self-adhesive, shape-transformable poly (L-lactide-co-ε-caprolactone) (BSS-PLCL) that can be triggered via thermal stimulation near physiological temperature (∼38 °C). Chemical inspections confirm the fundamental properties of the synthetic materials in diverse aspects, and study on mechanical and biochemical characteristics validates exceptional stretchability up to 800 % and tunable dissolution behaviors under biological conditions. The integration of the functional polymer with a bioresorbable electronic system highlights potential for a wide range of biomedical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sirtuin3 (SIRT3), a mitochondrial deacetylase, has been shown to be involved in various kidney diseases. In this study, we aimed to clarify the role of SIRT3 in cyclosporine-induced nephrotoxicity and the associated mitochondrial dysfunction. Madin-Darby canine kidney (MDCK) cells were transfected with Flag-tagged SIRT3 for SIRT3 overexpression or SIRT3 siRNA for the inhibition of SIRT3. Subsequently, the cells were treated with cyclosporine A (CsA) or vehicle. Wild-type and SIRT3 knockout (KO) mice were randomly assigned to receive cyclosporine A or olive oil. Furthermore, SIRT3 activator, honokiol, was treated alongside CsA to wild type mice. Our results revealed that CsA treatment inhibited mitochondrial SIRT3 expression in MDCK cells. Inhibition of SIRT3 through siRNA transfection exacerbated apoptosis, impaired the expression of the AMP-activated protein kinase-peroxisome proliferator-activated receptor gamma coactivator 1 alpha (AMPK-PGC1α) pathway, and worsened mitochondrial dysfunction induced by CsA treatment. Conversely, overexpression of SIRT3 through Flag-tagged SIRT3 transfection ameliorated apoptosis, increased the expression of mitochondrial superoxide dismutase 2, and restored the mitochondrial regulator pathway, AMPK-PGC1α. In SIRT3 KO mice, CsA treatment led to aggravated kidney dysfunction, increased kidney tubular injury, and accumulation of oxidative end products indicative of oxidative stress injury. Meanwhile, SIRT3 activation in vivo significantly mitigated these adverse effects, improving kidney function, reducing oxidative stress markers, and enhancing mitochondrial health following CsA treatment. Overall, our findings suggest that SIRT3 plays a protective role in alleviating mitochondrial dysfunction caused by CsA through the activation of the AMPK-PGC1α pathway, thereby preventing further kidney injury., (© 2024. The Author(s).)

Background: Endostatin is released during extracellular matrix remodeling and is involved in the development of vascular pathology and cardiovascular (CV) disease. However, the role of circulating endostatin as a biomarker of vascular calcification and CV events in patients undergoing hemodialysis (HD) remains unclear., Methods: A total of 372 patients undergoing HD were prospectively recruited. Plasma endostatin levels were measured at baseline, and their associations with circulating mineral bone disease (MBD) biomarkers and abdominal aortic vascular calcification scores were analyzed. The primary endpoint was defined as a composite of CV and cardiac events., Results: Plasma levels of patients in endostatin tertile 3 were significantly associated with low-density lipoprotein cholesterol levels and predialysis systolic blood pressure in multivariate analysis. However, endostatin levels did not correlate with circulating MBD biomarkers or vascular calcification scores. Patients in endostatin tertile 3 had a significantly higher cumulative event rate for the composite of CV events (p = 0.006). Endostatin tertile 3 was also associated with an increased cumulative rate of cardiac events (p = 0.04). In multivariate Cox regression analyses, endostatin tertile 3 was associated with a 4.37-fold risk for composite CV events and a 3.88-fold risk for cardiac events after adjusting for multiple variables., Conclusion: Higher circulating endostatin levels were independently associated with atherosclerotic risk factors but did not correlate with MBD markers or vascular calcification. Higher circulating endostatin levels were associated with a greater risk of composite CV events in patients undergoing HD, and endostatin is a biomarker that helps to determine the high risk of CV events.

Background: Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly., Methods: We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease., Results: During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13-1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84-1.11), 1.10 (0.96-1.27), 1.24 (1.06-1.45), 1.37 (1.12-1.66), and 1.99 (1.42-2.79), respectively (p for trend < 0.001)., Conclusion: In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.

Background: The prevalence of dementia is 2- to 7-fold higher among patients with end-stage kidney disease (ESKD) than among the general population; however, its clinical implications in this population remain unclear. Therefore, this study aimed to determine whether comorbid dementia increases mortality among older patients with ESKD undergoing newly initiated hemodialysis., Methods: We analyzed data from the Korean Society of Geriatric Nephrology retrospective cohort, which included 2,736 older ESKD patients (≥70 years old) who started hemodialysis between 2010 and 2017. Kaplan-Meier survival and Cox regression analyses were used to examine all-cause mortality between the patients with and without dementia in this cohort., Results: Of the 2,406 included patients, 8.3% had dementia at the initiation of dialysis; these patients were older (79.6 ± 6.0 years) than patients without dementia (77.7 ± 5.5 years) and included more women (male:female, 89:111). Pre-ESKD diagnosis of dementia was associated with an increased risk of overall mortality (hazard ratio, 1.503; p < 0.001), and this association remained consistent after multivariate adjustment (hazard ratio, 1.268; p = 0.009). In subgroup analysis, prevalent dementia was associated with mortality following dialysis initiation in female patients, those aged <85 years, those with no history of cerebrovascular accidents or severe behavioral disorders, those not residing in nursing facilities, and those with no or short-term hospitalization., Conclusion: A pre-ESKD diagnosis of dementia is associated with mortality following dialysis initiation in older Korean population. In older patients with ESKD, cognitive assessment at dialysis initiation is necessary.

Substrates or encapsulants in soft and stretchable formats are key components for transient, bioresorbable electronic systems; however, elastomeric polymers with desired mechanical and biochemical properties are very limited compared to non-transient counterparts. Here, we introduce a bioresorbable elastomer, poly(glycolide-co-ε-caprolactone) (PGCL), that contains excellent material properties including high elongation-at-break (< 1300%), resilience and toughness, and tunable dissolution behaviors. Exploitation of PGCLs as polymer matrices, in combination with conducing polymers, yields stretchable, conductive composites for degradable interconnects, sensors, and actuators, which can reliably function under external strains. Integration of device components with wireless modules demonstrates elastic, transient electronic suture system with on-demand drug delivery for rapid recovery of post-surgical wounds in soft, time-dynamic tissues., (© 2024. The Author(s).)

The early mortality rate in elderly patients undergoing hemodialysis is more than twice that in young patients, requiring more specialized healthcare. We investigated whether the number of professional dialysis specialists affected early mortality in elderly patients undergoing hemodialysis. This multicenter retrospective cohort study analyzed data from 1860 patients aged ≥ 70 years who started hemodialysis between January 2010 and December 2017. Study regions included Seoul, Gyeonggi-do, Gangwon-do, Daejeon/Chungcheong-do, Daegu/Gyeongsangbuk-do, and Busan/Ulsan/Gyeongsangnam-do. The number of patients undergoing hemodialysis per dialysis specialist was calculated using registered data from each hemodialysis center. Early mortality was defined as death within 6 months of hemodialysis initiation. Gangwon-do (28.3%) and Seoul (14.5%) showed the highest and lowest early mortality rate, respectively. Similarly, Gangwon-do (64.6) and Seoul (43.9) had the highest and lowest number of patients per dialysis specialist, respectively. Relatively consistent results were observed for the regional rankings of early mortality rate and number of patients per dialysis specialist. Multivariate Cox regression analysis-adjusted for previously known significant risk factors-revealed that the number of patients per dialysis specialist was an independent risk factor for early mortality (hazard ratio: 1.031, p < 0.001). This study underscores the growing need for dialysis specialists for elderly hemodialysis patients in Korea., (© 2024. The Author(s).)

Introduction: End-stage renal disease (ESRD) is a growing disease worldwide, including Korea. This is an important condition that affects patient outcome. To provide optimal management for mineral disturbance, vascular calcification, and bone disease in ESRD patients, the Korean dialysis cohort for mineral, vascular calcification, and fracture (ORCHESTRA) study was conducted by enrolling Korean dialysis patients., Methods: Sixteen university-affiliated hospitals and one Veterans' Health Service Medical Center participated in this study. This prospective cohort study enrolled approximately 900 consecutive patients on dialysis between May 2019 and January 2021. Enrolled subjects were evaluated at baseline for demographic information, laboratory tests, radiologic imaging, and bone mineral densitometry (BMD) scans. After enrollment, regular assessments of the patients were performed, and their biospecimens were collected according to the study protocol. The primary outcomes were the occurrence of major adverse cardiovascular events, invasive treatment for peripheral artery disease, and osteoporotic fractures. The secondary outcomes were hospitalization for cerebrovascular disease or progression of abdominal aortic calcification. Participants will be assessed for up to 3 years to determine whether primary or secondary outcomes occur., Results: Between May 2019 and January 2021, all participating centers recruited 900 consecutive dialysis patients, including 786 undergoing hemodialysis (HD) and 114 undergoing peritoneal dialysis (PD). The mean age of the subjects was 60.4 ± 12.3 years. Males accounted for 57.7% of the total population. The mean dialysis vintage was 6.1 ± 6.0 years. The HD group was significantly older, had a longer dialysis vintage, and more comorbidities. Overall, the severity of vascular calcification was higher and the level of BMD was lower in the HD group than in the PD group., Conclusion: This nationwide, multicenter, prospective cohort study focused on chronic kidney disease-mineral and bone disorder and aimed to provide clinical evidence to establish optimal treatment guidelines for Asian dialysis patients., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

The rapid growth of the elderly population is making the need for extensive and advanced information about age-related organ dysfunction a crucial research area. The kidney is one of the organs most affected by aging. Aged kidneys undergo functional decline, characterized by a reduction in kidney size, decreased glomerular filtration rate, alterations in renal blood flow, and increased inflammation and fibrosis. This review offers a foundation for understanding the functional and molecular mechanisms of aging kidneys and for selecting identifying appropriate targets for future treatments of age-related kidney issues.

Background: Hypertension is a major cardiovascular risk factor in hemodialysis patients. This study identified the optimal blood pressure (BP) target for Korean hemodialysis patients using the Korean Renal Dialysis System (KORDS) dataset from the Korean Society of Nephrology and a pooled analysis for previous studies., Methods: Hemodialysis patients were classified according to their systolic (SBP) and diastolic BP (DBP) at intervals of 20 and 10 mmHg, respectively. As a primary and secondary outcome, all-cause mortality and cardiovascular mortality were evaluated. Subsequently, pooled analysis with previous literatures was performed., Results: Among 70,607 patients, 13,708 (19.4%) died in 2,426 days (interquartile range, 1,256-4,075 days). Mean SBP and DBP were 143.0 ± 19.6 and 78.5 ± 12.0 mmHg. In multivariable Cox regression, the patients with SBP of <120 and ≥180 mmHg showed 1.10- and 1.12-times increased risk of all-cause mortality compared to SBP of 120-140 mmHg. Meanwhile, DBP showed no significant association. In subgroup analysis, patients aged <70 years and without diabetes had a U-shaped SBP-mortality association. Cardiovascular mortality was increased in SBP of ≥160 mmHg compared to 120-140 mmHg, but it was not in <120 mmHg. Pooled analysis with previous studies mostly showed elevated risk in SBP of <120 mmHg, but the risks in 140-160 and 160-180 mmHg were not consistent., Conclusion: Extremely lowering BP (<120 mmHg) or uncontrolled hypertension (≥160 mmHg) should be avoided to optimize survival in Korean hemodialysis patients. Detailed analysis for patients with SBP of 120-160 mmHg should be studied further under uniform BP measurement, along with consideration of risk of intradialytic hypotension. Tailored recommendations regarding patient risk factors also should be considered.

Inflammation plays a major role in the pathogenesis of chronic kidney disease (CKD), but the relationship between systemic inflammation and CKD-mineral bone disease is unclear. We aimed to investigate whether the neutrophil-to-lymphocyte ratio (NLR) is related to abdominal aortic calcification (AAC) and bone mineral density (BMD) in dialysis patients. In this cross-sectional analysis using baseline data of a multicenter cohort, a total of 759 patients were divided into three groups according to NLR level, and the associations between NLR and Kauppila AAC score (AACS) and BMD were assessed. The highest tertile NLR group had more males, alcohol consumers, higher diabetes prevalence, and higher comorbidity index than the lowest tertile NLR group. Fasting glucose and C-reactive protein levels were higher, while serum albumin, serum iron, and lipid profiles except triglycerides were lower in the highest tertile group. AACS was significantly higher in the highest tertile group than in the lowest and middle tertile groups (p = 0.017), but the mean areal BMD and T-score of the lumbar spine and femur were not different between groups. NLR level was positively correlated with AACS in all aortic wall segments except L1 and L3 anterior. In multivariable logistic regression analysis, the highest tertile NLR group was independently associated with AAC (odds ratio 2.876, 95% confidence interval 1.250-6.619, p = 0.013) but was not associated with osteoporosis in the lumbar spine and femur after adjusting for confounding factors. The NLR can be used as a potential indicator of AAC in dialysis patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ban et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: This study aimed to analyze low-density lipoprotein cholesterol (LDL-C) levels and their relationship with mortality in order to identify the appropriate lipid profile for older Korean hemodialysis patients., Methods: We enrolled a total of 2,732 incident hemodialysis patients aged > 70 years from a retrospective cohort of the Korean Society of Geriatric Nephrology from 2010 Jan to 2017 Dec, which included 17 academic hospitals in South Korea. Of these patients, 1,709 were statin-naïve, and 1,014 were analyzed after excluding those with missing LDL-C level data. We used multivariate Cox regression analysis to select risk factors from 20 clinical variables among the LDL-C groups., Results: The mean age of the entire patient population was 78 years, with no significant differences in age between quartiles Q1 to Q4. However, the proportion of males decreased as the quartiles progressed towards Q4 (p < 0.001). The multivariate Cox regression analysis, which included all participants, showed that low LDL-C levels were associated with all-cause mortality. In the final model, compared to Q1, the hazard ratios (95% confidence interval) were 0.77 (0.620-0.972; p = 0.027), 0.85 (0.676-1.069; p = 0.166), and 0.65 (0.519-0.824; p < 0.001) for Q2, Q3, and Q4, respectively, after adjusting for covariates, such as conventional and age-specific risk factors. The final model demonstrated that all-cause mortality increased as LDL-C levels decreased, as confirmed by a restrictive cubic spline plot., Conclusions: In older hemodialysis patients who had not previously received dyslipidemia treatment, elevated LDL-C levels were not associated with increased all-cause mortality. Intriguingly, lower LDL-C levels appear to be associated with an unfavorable effect on all-cause mortality among high-risk hemodialysis patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Although knowledge of the genetic factors influencing kidney disease is increasing, epigenetic profiles, which are associated with chronic kidney disease (CKD), have not been fully elucidated. We sought to identify the DNA methylation status of CpG sites associated with reduced kidney function and examine whether the identified CpG sites are associated with CKD development., Method: We analyzed DNA methylation patterns of 440 participants in the Korean Genome and Epidemiology Study (KoGES) with estimated glomerular filtration rates (eGFRs) ≥ 60 mL/min/1.73 m 2 at baseline. CKD development was defined as a decrease in the eGFR of <60 at any time during an 8-year follow-up period ("CKD prediction" analysis). In addition, among the 440 participants, 49 participants who underwent a second methylation profiling were assessed for an association between a decline in kidney function and changes in the degree of methylation of CpG sites during the 8 years ("kidney function slope" analysis)., Results: In the CKD prediction analysis, methylation profiles of a total of 403,129 CpG sites were evaluated at baseline in 440 participants, and increased and decreased methylation of 268 and 189 CpG sites, respectively, were significantly correlated with the development of CKD in multivariable logistic regression. During kidney function slope analysis using follow-up methylation profiles of 49 participants, the percent methylation changes in 913 CpG sites showed a linear relationship with the percent change in eGFR during 8 years. During functional enrichment analyses for significant CpG sites found in the CKD prediction and kidney function slope analyses, we found that those CpG sites represented MAPK, PI3K/Akt, and Rap1 pathways. In addition, three CpG sites from three genes, NPHS2 , CHCHD4 , and AHR , were found to be significant in the CKD prediction analysis and related to a decline in kidney function., Conclusion: It is suggested that DNA methylation on specific genes is associated with the development of CKD and the deterioration of kidney function., Competing Interests: The authors declare no conflict of interest.

Deteriorating kidney function is frequently observed in the elderly population, as well as vulnerability to acute kidney failure, such as ischemic/reperfusion injury (IRI), and inadequate recovery from IRI is one of the mechanisms of kidney dysfunction in the elderly. The potential mediators in the progression of kidney dysfunction in the aging kidney have not yet been clearly revealed. In this study, we investigated the role of nuclear factor erythroid 2-related factor 2 (NRF2), which is an essential regulator of cellular redox homeostasis, in restoring kidney function after IRI in the aging kidney. NRF2 expression decreased significantly in the kidneys of old mice, as well as histologic and functional renal recovery after IRI; 45-min renal pedicle clamping was retarded in old compared with young mice. Persistent renal injury during the recovery phase after IRI was aggravated in NRF2 knockout (KO) mice compared to wild-type mice. Oxidative stress occurred in NRF2 KO old mice during the IRI recovery phase along with decreased expression of mitochondrial OXPHOS-related proteins and a reduction in mitochondrial ATP content. In vitro, hypoxia/reoxygenation (H/R) injury was aggravated in senescent human proximal tubuloepithelial cells after NRF2 restriction using NRF2 siRNA, which also increased the level of oxidative stress and deteriorated mitochondrial dysfunction. Treating the mice with an NRF2 activator, CDDO-Me, alleviated the injury. These results suggest that NRF2 may be a therapeutic target for the aging kidney.

Background: Patients with kidney failure must make complicated decisions about the dialysis modalities used either at home or in-hospital. Different options have varying levels of impact on patients' physical and psychological conditions and their social life. The purpose of this study was to evaluate the implementation of an intervention designed to achieve shared decision making (SDM) in patients' options for dialysis., Methods: SDM was performed after consent was written for stage 5 chronic kidney disease patients before dialysis, and 435 cases were performed in 408 patients from December 16, 2019 to June 30, 2021. Among these, 101 patients were compared by SDM measurement scale, patient satisfaction, disease recognition scale survey, and dialysis method., Results: The average age of participants was 56 years, with a gender composition of 55 males (54.5%) and 46 females (45.5%). Following SDM, the final dialysis methods decided upon by patients and clinicians were peritoneal dialysis (67 patients, 66.3%), hemodialysis (22 patients, 21.8%), and kidney transplantation (1 patient, 1.0%)., Conclusions: Among participating patients, SDM was effective when used to decide on dialysis treatment, and patients were satisfied with the dialysis method decision process. On the disease awareness scale, those who participated in this project had relatively high positive and low negative perceptions, so it can be concluded that SDM was relatively effective. The implementation of SDM was helpful in selecting patients' best dialysis methods, and SDM scale results were higher in the peritoneal dialysis group than in the hemodialysis group., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

As rubber-like elastomers have led to scientific breakthroughs in soft, stretchable characteristics-based wearable, implantable electronic devices or relevant research fields, developments of degradable elastomers with comparable mechanical properties could bring similar technological innovations in transient, bioresorbable electronics or expansion into unexplored areas. Here, we introduce ultra-stretchable, biodegradable elastomers capable of stretching up to ~1600% with outstanding properties in toughness, tear-tolerance, and storage stability, all of which are validated by comprehensive mechanical and biochemical studies. The facile formation of thin films enables the integration of almost any type of electronic device with tunable, suitable adhesive strengths. Conductive elastomers tolerant/sensitive to mechanical deformations highlight possibilities for versatile monitoring/sensing components, particularly the strain-tolerant composites retain high levels of conductivities even under tensile strains of ~550%. Demonstrations of soft electronic grippers and transient, suture-free cardiac jackets could be the cornerstone for sophisticated, multifunctional biodegradable electronics in the fields of soft robots and biomedical implants., (© 2023. The Author(s).)

Background: The rate of kidney function decline is different for each individual regardless of any difference in the medical histories. This study set out to identify the risk factors for high discordance in kidney function decline in an identical twin cohort., Methods: This study included 333 identical twins from the Korean Genome and Epidemiology Study who were categorized into two groups according to the estimated glomerular filtration rate (eGFR) decline: the slow and rapid progressor groups. The mean differences of variables were compared between the two groups. We calculated the difference in the annual eGFR change between twins and analyzed the risk factors associated with high discordance in twins who had > 5 mL/min/1.73 m2 /yr of the intra-twin difference in the annual eGFR decline. Identical twins with diabetes and baseline eGFR < 60 mL/min/1.73 m2 were excluded., Results: The high discordance twins showed significant differences in body mass index; waist-to-hip ratio; total body fat percentage; and levels of blood hemoglobin, serum fasting glucose, albumin, triglyceride, and uric acid; however, there were no differences in low discordance twins. Multivariable logistic regression showed that blood hemoglobin level is the only significant factor associated with high discordance of eGFR decline in twins., Conclusions: Blood hemoglobin level may play a role in the individual differences in kidney function decline., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hwang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Recent advances in passive radiative cooling systems describe a variety of strategies to enhance cooling efficiency, while the integration of such technology with a bioinspired design using biodegradable materials can offer a research opportunity to generate energy in a sustainable manner, favorable for the temperature/climate system of the planet. Here, we introduce stretchable and ecoresorbable radiative cooling/heating systems engineered with zebra stripe-like patterns that enable the generation of a large in-plane temperature gradient for thermoelectric generation. A comprehensive study of materials with theoretical evaluations validates the ability to accomplish the target performances even under external mechanical strains, while all systems eventually disappear under physiological conditions. Use of the zebra print for selective radiative heating demonstrates an unexpected level of temperature difference compared to use of radiative cooling emitters alone, which enables producing energy through resorbable silicon-based thermoelectric devices. The overall result suggests the potential of scalable, ecofriendly renewable energy systems.

Background: Physical activity (PA) is an important risk factor associated with health outcomes. However, the relationship between PA and kidney function decline in older adults remains unclear. We examined the influence of PA on kidney function decline and mortality in community-dwelling older adults., Methods: Adults aged ≥ 65 years with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m 2 who had available health checkup data from 2009 to 2010 were included. The cohort was followed annually through December 2015 for anthropometric, sociodemographic, and medical information including outcomes and biennially for laboratory information from the health checkup. We divided these patients into three groups according to self-reported PA (Inactive group: no leisure-time PA, Active group: vigorous activity for at least 80 min/week or a sum of moderate-intensity activity and walking for at least 300 min/week, Low-active group: level of PA between the definitions of the other two groups). Associations between the intensity of PA and death, cardiovascular death, and ≥ 50% eGFR decline were investigated., Results: Among 102,353 subjects, 32,984 (32.23%), 54,267 (53.02%), and 15,102 (14.75%) were classified into the inactive, low-active, and active groups, respectively. The active group was younger, contained a higher proportion of men, and had higher frequencies of hypertension, diabetes mellitus, drinking, and smoking than the other groups. The active group had significantly lower incidence rates of mortality, cardiovascular mortality, and kidney function decline than the other groups (all p < 0.001). The active group also showed lower all-cause (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.70-0.82) and cardiovascular mortality (HR, 0.64; 95% CI, 0.53-0.78) and protection against ≥ 50% eGFR decline (HR, 0.81; 95% CI, 0.68-0.97) compared with the inactive group in the fully adjusted Cox proportional hazards regression model., Conclusions: High PA was an independent modifiable lifestyle factor for reducing mortality and protecting against declines in kidney function in older adults., (© 2022. The Author(s).)

Obesity is a major health problem worldwide and is associated with chronic kidney disease (CKD). Body mass index (BMI) is a common method of diagnosing obesity, but there are concerns about its accuracy and ability to measure body composition. This study evaluated the risk of CKD development in a middle-aged population in association with various body composition metrics. From a prospective cohort of 10,030 middle-aged adults, we enrolled 6727 for whom baseline and follow-up data were available. We collected data pertaining to participants' BMI, manually measured waist-hip ratio (WHR), and various measurements of bioelectrical impedance analysis (BIA), including total body fat content, muscle content, and calculated WHR, and classified the participants into quintiles accordingly. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m 2 in follow-up laboratory tests. While an increase in BMI, WHR, and total body fat were associated with an elevated risk of CKD, an increase in total body muscle decreased the risk. Among the body composition metrics, WHR measured by BIA had the highest predictive value for CKD (C-statistics: 0.615). In addition, participants who were "healthy overweight, (defined as low WHR but high BMI), exhibited a 62% lower risk of developing CKD compared to those with "normal-weight obesity," (defined as high WHR despite a normal BMI). In conclusion, we suggest that central obesity measured by BIA is a more accurate indicator than BMI for predicting the development of CKD., (© 2022. The Author(s).)

Background: Serum creatinine and cystatin C are not only good indicators of renal function but have also been confirmed to be related to disease prognosis and mortality in various diseases via creatinine/cystatin C ratio (CCR). However, although they are biomarkers of renal function, there is no study regarding renal impairment as a confounding variable in the relationship between CCR and all-cause mortality., Methods: Patients who had simultaneous measurements of serum creatinine and cystatin C between 2003 and 2020 were enrolled. The patients with chronic kidney disease (CKD) were defined as having an estimated glomerular filtration rate (eGFR) CKD-EPI Cr-Cystatin C < 60 ml/min/1.73 m 2 . CCR was calculated by dividing the serum creatinine level by the cystatin C level measured on the same day. The main outcome assessed was all-cause mortality according to CCR in CKD or non-CKD groups., Results: Among the 8,680 patients in whom creatinine and cystatin C levels were measured simultaneously, 4,301 were included in the CKD group, and 4,379 were included in the non-CKD group, respectively. CCR was 1.4 ± 0.6 in total participants. The non-CKD group showed higher mean CCR, (1.5 ± 0.7 vs. 1.3 ± 0.5) as well as a wider distribution of CCR ( p < 0.001) when compared to the CKD group. In non-CKD group, 1 st , 4 th and 5 th quintiles of CCR significantly increased the all-cause mortality risk compared to 2 nd quintile of CCR, suggesting U-shaped mortality risk according to CCR in non-CKD. On the other hand, in CKD group, the risk of all-cause mortality linearly increased and 5 th quintile of CCR showed 1.82 times risk of mortality compared to 2 nd quintile of CCR. In the subgroup analysis of mortality by age and sex, the mortality difference according to CCR were diminished in old age and female sex subgroups., Conclusion: We discovered a U-shaped relationship between mortality and CCR levels in normal renal function, and an increased risk of mortality in CKD with elevated CCR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hwang, Song, Shin, Cho, Ahn, Ko, Kwon and Kim.)

Background: Evidence of the ethical appropriateness and clinical benefits of shared decision-making (SDM) are accumulating. This study aimed to not only identify physicians' perspectives on SDM, and practices related to end-of-life care in particular, but also to gauge the effect of SDM education on physicians in Korea., Methods: A 14-item questionnaire survey using a modified Delphi process was delivered to nephrologists and internal medicine trainees at 17 university hospitals., Results: A total of 309 physicians completed the survey. Although respondents reported that 69.9% of their practical decisions were made using SDM, 59.9% reported that it is not being applied appropriately. Only 12.3% of respondents had received education on SDM as part of their training. The main obstacles to appropriate SDM were identified as lack of time (46.0%), educational materials and tools (29.4%), and education on SDM (24.3%). Although only a few respondents had received training on SDM, the proportion of those who thought they were using SDM appropriately in actual practice was high; the proportion of those who chose lack of time and education as factors that hindered the proper application of SDM was low., Conclusion: The majority of respondents believed that SDM was not being implemented properly in Korea, despite its use in actual practice. To improve the effectiveness of SDM in the Korean medical system, appropriate training programs and supplemental policies that guarantee sufficient application time are required.

The role of statins in chronic kidney disease (CKD) has been extensively evaluated, but it remains controversial in specific population such as dialysis-dependent CKD. This study examined the effect of statins on mortality in CKD patients using two large databases. In data from the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) from two hospitals, CKD was defined as an estimated glomerular filtration rate < 60 mL/min/m 2 ; we compared survival between patients with or without statin treatment. As a sensitivity analysis, the results were validated with the Korea National Health Insurance (KNHI) claims database. In the analysis of CDM datasets, statin users showed significantly lower risks of all-cause and cardiovascular mortality in both hospitals, compared to non-users. Similar results were observed in CKD patients from the KNHI claims database. Lower mortality in the statin group was consistently evident in all subgroup analyses, including patients on dialysis and low-risk young patients. In conclusion, we found that statins were associated with lower mortality in CKD patients, regardless of dialysis status or other risk factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kim, Choi, Oh, Kim, Jo, Cho, Ahn, Kwon and Ko.)

Contrast-induced nephropathy (CIN) is an impairment of renal function that occurs after the administration of an iodinated contrast medium (CM). Kidney dysfunction in CIN is considered transient and reversible in most cases. However, it is the third most common cause of hospital-acquired acute kidney injury and is associated with increased morbidity and mortality, especially in high-risk patients. Diagnostic and interventional procedures that require intravascular CM are being used with increasing frequency, especially among the elderly, who can be particularly susceptible to CIN due to multiple comorbidities. Therefore, identifying the exact mechanisms of CIN and its associated risk factors is crucial not only to provide optimal preventive management for at-risk patients, but also to increase the feasibility of diagnostic and interventional procedure that use CM. CM induces kidney injury by impairing renal hemodynamics and increasing the generation of reactive oxygen species, in addition to direct cytotoxicity. Periprocedural hydration is the most widely accepted preventive strategy to date. Here, we review the latest research results on the pathophysiology and management of CIN.

Metabolic syndrome is a cluster of metabolic indicators that increase the risk of diabetes and cardiovascular diseases. Visceral obesity and factors derived from altered adipose tissue, adipokines, play critical roles in the development of metabolic syndrome. Although the adipokines leptin and adiponectin improve insulin sensitivity, others contribute to the development of glucose intolerance, including visfatin, fetuin-A, resistin, and plasminogen activator inhibitor-1 (PAI-1). Leptin and adiponectin increase fatty acid oxidation, prevent foam cell formation, and improve lipid metabolism, while visfatin, fetuin-A, PAI-1, and resistin have pro-atherogenic properties. In this review, we briefly summarize the role of various adipokines in the development of metabolic syndrome, focusing on glucose homeostasis and lipid metabolism.

Obstructive uropathy is known to be associated with acute kidney injury (AKI). This study aimed to investigate the etiologies, clinical characteristics, consequences and also assess the impact of AKI on long-term outcomes. This multicenter, retrospective study of 1683 patients with obstructive uropathy who underwent percutaneous nephrostomy (PCN) analyzed clinical characteristics, outcomes including progression to end-stage kidney disease (ESKD), overall mortality, and the impact of AKI on long-term outcomes. Obstructive uropathy in adults was most commonly caused by malignancy, urolithiasis, and other causes. AKI was present in 78% of the patients and was independently associated with preexisting chronic kidney disease (CKD). Short-term recovery was achieved in 56.78% after the relief of obstruction. ESKD progression rate was 4.4% in urolithiasis and 6.8% in other causes and older age, preexisting CKD, and stage 3 AKI were independent factors of progression. The mortality rate (34%) was highly attributed to malignant obstruction (52%) stage 3 AKI was also an independent predictor of mortality in non-malignant obstruction. AKI is a frequent complication of adult obstructive uropathy. AKI negatively affects long-term kidney outcomes and survival in non-malignant obstructions. A better understanding of the epidemiology and prognostic factors is needed for adult obstructive uropathy., (© 2021. The Author(s).)

Pseudomonas aeruginosa is a ubiquitous human pathogen that causes severe infections. Although antibiotics, such as tobramycin, are currently used for infection therapy, their antibacterial activity has resulted in the emergence of multiple antibiotic-resistant bacteria. The 6-gingerol analog, a structural derivative of the main component of ginger, is a quorum sensing (QS) inhibitor. However, it has a lower biofilm inhibitory activity than antibiotics and the possibility to cause toxicity in humans. Therefore, novel and more effective approaches for decreasing dosing concentration and increasing biofilm inhibitory activity are required to alleviate P. aeruginosa infections. In this study, a 6-gingerol analog was combined with tobramycin to treat P. aeruginosa infections. The combined treatment of 6-gingerol analog and tobramycin showed strong inhibitory activities on biofilm formation and the production of QS-related virulence factors of P. aeruginosa compared to single treatments. Furthermore, the combined treatment alleviated the infectivity of P. aeruginosa in an insect model using Tenebrio molitor larvae without inducing any cytotoxic effects in human lung epithelial cells. The 6-gingerol analog showed these inhibitory activities at much lower concentrations when used in combination with tobramycin. Adjuvant effects were observed through increased QS-disrupting processes rather than through antibacterial action. In particular, improved RhlR inactivation by this combination is a possible target for therapeutic development in LasR-independent chronic infections. Therefore, the combined treatment of 6-gingerol analog and tobramycin may be considered an effective method for treating P. aeruginosa infections. IMPORTANCE Pseudomonas aeruginosa is a pathogen that causes various infectious diseases through quorum-sensing regulation. Although antibiotics are mainly used to treat P. aeruginosa infections, they cause the emergence of resistant bacteria in humans. To compensate for the disadvantages of antibiotics and increase their effectiveness, natural products were used in combination with antibiotics in this study. We discovered that combined treatment with 6-gingerol analog from naturally-derived ginger substances and tobramycin resulted in more effective reductions of biofilm formation and virulence factor production in P. aeruginosa than single treatments. Our findings support the notion that when 6-gingerol analog is combined with tobramycin, the effects of the analog can be exerted at much lower concentrations. Furthermore, its improved LasR-independent RhlR inactivation may serve as a key target for therapeutic development in chronic infections. Therefore, the combined treatment of 6-gingerol analog and tobramycin is suggested as a novel alternative for treating P. aeruginosa infections.

Background: Hemodialysis is a life-saving renal replacement treatment for patients with chronic kidney disease, but various complications occur during hemodialysis and associated procedures. This study was conducted to analyze the specific characteristics of hemodialysis-related complications and malpractice that have led to legal disputes., Methods: Judgments from cases litigated between 1991 and 2019 due to complications related to hemodialysis or vascular access were analyzed using the database of the Korean Supreme Court Judgment System., Results: Of 32 dialysis-related litigation cases, 14 cases were dismissed and malpractice was recognized in 18 cases. Among all cases and those in which malpractice was recognized, the most common clinical complication was associated with central venous catheter (CVC) insertion (25.0% and 42.9%, respectively). In 22 of 32 (68.8%) cases, complications occurred before or after (not during) dialysis, and performance error was the most common clinical error leading to legal disputes (58.3%). Complications resulted in death in 59.4% of cases, and CVC-related complications were associated with the largest proportion (63.2%) of deaths., Conclusions: Hemodialysis was implicated in various medical disputes, and CVC-related complications were the most common and serious adverse events. Clinicians' awareness of the incidence and severity of possible complications of hemodialysis procedures should be increased., Competing Interests: The authors have declared that no competing interests exist.

Several studies have demonstrated the nephroprotective effects of estrogen on renal damage. In light of the inconsistent results of previous findings, this study aims to evaluate the in-depth role of menopausal hormone therapy (MHT) on the development of end stage renal disease (ESRD). 3,109,506 Korean adult women who had undergone a medical examination in 2009 (index year) were initially identified for inclusion in this study. We excluded subjects had not experienced menopause naturally, had data missing for at least one variable, and were diagnosed with ESRD within 1 year from the index year. MHT data was obtained from self-reporting questionnaires and the primary outcome was the development of ESRD from the index year until December 31, 2018. A final total of 1,460,311 subjects were included in this study. The participants were divided into four groups according to the duration of MHT; no history of MHT, MHT < 2 years, 2 ≤ MHT < 5 years, MHT ≥ 5 years. During the 9-year study period, a total of 4905 participants developed ESRD. The participants who had a history of MHT use were found to have a 30% reduced risk of developing ESRD. Results from the subgroup analyses were similar to that of the primary study. The findings in this study demonstrate the beneficial effects of MHT on the development of ESRD in postmenopausal women. Based on results, our study may offer suggestions for further studies to investigate the therapeutic options on kidney disease., (© 2021. The Author(s).)

Background/aims: Elevated levels of serum myostatin have been proposed as a biomarker for sarcopenia. Recent studies have shown that elevated level of serum myostatin was associated with physical fitness and performance. This study aimed to examine the significance of myostatin in the association between muscle mass and physical performance in the elderly., Methods: This cross-sectional study is based on the Korean Frailty and Aging Cohort study involving 1053 people aged 70 years or over. Anthropometric, physical performance, and laboratory data were collected., Results: The mean age of the participants was 75.8 years, and 50.7% of them were female. Serum myostatin levels in men (3.7 ± 1.2 vs. 3.2 ± 1.1 ng/mL, p < 0.001) were higher compared with that in women. Serum myostatin level was associated with appendicular skeletal muscle mass (ASM) index and eGFR by cystatin C. Serum myostatin/ASM ratio was associated with handgrip strength in women., Conclusion: Higher serum myostatin levels were related with higher muscle mass and better physical performances in the elderly. Serum myostatin/ASM ratio may be a predictor for physical performance rather than myostatin.

Background: Intradialytic hypotension (IDH) has been reported to be an important prognostic factor in hemodialysis patients. However, a standard definition of IDH has not yet been determined., Methods: We retrospectively analyzed blood pressure (BP) metrics obtained during serial dialysis sessions over a 90-day period from a single dialysis center from 2016 to 2017. The mean values and the frequency of specific values of BP were analyzed as predictors of 3-year mortality., Results: A total of 430 patients who underwent maintenance dialysis were included. The mean age was 63.3 ± 12.4 years and 58.6% were male. A low minimum systolic blood pressure (SBP) <110 mmHg during dialysis was significantly associated with increased all-cause mortality. The frequency of a minimum SBP <100 mmHg was the most significant predictor of 3-year mortality, with an area under the curve (AUC) of 0.722. Furthermore, the frequency of a minimum SBP <100 mmHg significantly increased the predictability of mortality when combined with the presence of other clinical factors including age, body mass index and vascular access type (AUC 0.786 vs. 0.835; p = 0.005)., Conclusion: Among the various intradialytic BP metrics, the frequency of a minimum SBP <100 mmHg is the most significant factor related to all-cause mortality. The guidelines for the management of blood pressure in dialysis patients should consider including a minimum SBP <100 mmHg as a definition for IDH., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

High dietary protein intake may lead to increased intraglomerular pressure and glomerular hyperfiltration, which in the long-term can lead to de novo or aggravating preexisting chronic kidney disease (CKD). Hence, a low protein diet (LPD, 0.6 to 0.8 g/kg/day) is recommended for the management of CKD. There are evidences that dietary protein restriction mitigate progression of CKD and retard the initiation of dialysis or facilitate incremental dialysis. LPD is also helpful to control metabolic derangements in CKD such as metabolic acidosis and hyperphosphatemia. Recently, a growing body of evidence has emerged on the benefits of plant-dominant low-protein diet (PLADO), which composed of > 50% plant-based sources. PLADO is considered to be helpful for relieving uremic burden and metabolic complications in CKD compared to animal protein dominant consumption. It may also lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation along with reducing cardiovascular risk. Alleviation of constipation in PLADO may minimize the risk of hyperkalemia. A balanced and individualized dietary approach for good adherence to LPD utilizing various plant-based sources as patients' preference should be elaborated for the optimal care in CKD. Periodic nutritional assessment under supervision of trained dietitians should be warranted to avoid protein-energy wasting.

Background: Neprilysin inhibition has demonstrated impressive benefits in heart failure treatment, and is the current focus of interest in cardiovascular (CV) and kidney diseases. However, the role of circulating neprilysin as a biomarker for CV events is unclear in hemodialysis (HD) patients. Methods: A total of 439 HD patients from the K-cohort were enrolled from June 2016 to April 2019. The plasma neprilysin level and echocardiographic findings at baseline were examined. The patients were prospectively followed up to assess the primary endpoint (composite of CV events and cardiac events). Results: Plasma neprilysin level was positively correlated with left ventricular (LV) mass index, LV end-systolic volume, and LV end-diastolic volume. Multivariate linear regression analysis revealed that neprilysin level was negatively correlated with LV ejection fraction (β = -2.14; p = 0.013). The cumulative event rate of the composite of CV events was significantly greater in neprilysin tertile 3 ( p = 0.049). Neprilysin tertile 3 was also associated with an increased cumulative event rate of cardiac events ( p = 0.016). In Cox regression analysis, neprilysin tertile 3 was associated with a 2.61-fold risk for the composite of CV events [95% confidence interval (CI), 1.37-4.97] and a 2.72-fold risk for cardiac events (95% CI, 1.33-5.56) after adjustment for multiple variables. Conclusions: Higher circulating neprilysin levels independently predicted the composite of CV events and cardiac events in HD patients. The results of this study suggest the importance of future studies on the effect of neprilysin inhibition in reducing CV events., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hwang, Kim, Kim, Lee, Lee, Ahn, Moon, Lee, Ko and Jeong.)

Osteoporosis is a major public health concern, especially in women. This study aims to identify early biomarkers from biochemical measurements of serum and urine for recognizing the development of osteoporosis and osteopenia in premenopausal and postmenopausal women. From the Korean Genome and Epidemiology Study (KoGES) cohort, longitudinal study participants with normal bone density were enrolled and assessed for the association of baseline clinical and biochemical factors with osteoporosis development over 4 years. In addition, a cross-sectional study between normal bone density and osteopenia/osteoporosis was conducted to validate the risk factors found in the longitudinal cohort. Of the 5272 female participants in the KoGES cohort, 813 women (501 premenopausal and 312 menopausal) who had normal bone density at baseline were included in the longitudinal study. During the 4 years of follow-up, 64 patients developed osteoporosis and 354 developed osteopenia. In a multivariate logistic regression analysis, serum calcium and urine uric acid levels were significantly associated with elevated osteoporosis risk in premenopausal and postmenopausal women, respectively (risk of osteoporosis by serum calcium levels in premenopausal women: 4.03 (1.09-14.93), p = 0.037; risk of osteoporosis by urine uric acid levels in postmenopausal women: 24.08 (1.79-323.69), p = 0.016). For the cross-sectional study, serum and urine parameters were compared between women with osteopenia or osteoporosis at baseline and those with normal bone density. Urine uric acid levels were found to be significantly higher in both premenopausal and postmenopausal women with bone loss than in women with normal bone density ( p < 0.001 and p = 0.004, respectively). Uric acid level in urine may be an early marker for the development of osteoporosis in women, especially after menopause.

Endocan, a potential biomarker of endothelial dysfunction, is associated with increased cardiovascular risk. We investigated the utility of plasma endocan for predicting cardiovascular risk in end-stage renal disease (ESRD) patients undergoing hemodialysis. Of the 452 patients in the K-cohort, 354 with available plasma endocan levels were enrolled. The correlation between plasma endocan levels and the clinical characteristics of a study population were analyzed. We divided patients into two groups, according to plasma endocan levels, and investigated the predictive value of endocan for the occurrence of cardiovascular events. In a multiple linear regression analysis, plasma endocan levels were positively correlated with previous cardiovascular events and negatively correlated with body mass index, albumin, and triglyceride. Patients with higher plasma endocan levels experienced more frequent cardiovascular events than those with lower plasma endocan levels (12.9% in the lower group vs. 22.7% in the higher group, p = 0.016). Cox proportional hazard models showed that higher plasma endocan levels were an independent predictor of cardiovascular events in ESRD patients on hemodialysis ((hazard ration) HR 1.949, 95% (confidence interval) CI 1.144-3.319, p = 0.014). Our results suggest that plasma endocan level might be a useful biomarker for predicting cardiovascular events in ESRD patients on hemodialysis.

Sirtuins (SIRTs) are class III histone deacetylases (HDACs) that play important roles in aging and a wide range of cellular functions. Sirtuins are crucial to numerous biological processes, including proliferation, DNA repair, mitochondrial energy homeostasis, and antioxidant activity. Mammals have seven different sirtuins, SIRT1-7, and the diverse biological functions of each sirtuin are due to differences in subcellular localization, expression profiles, and cellular substrates. In this review, we summarize research advances into the role of sirtuins in the pathogenesis of various kidney diseases including acute kidney injury, diabetic kidney disease, renal fibrosis, and kidney aging along with the possible underlying molecular mechanisms. The available evidence indicates that sirtuins have great potential as novel therapeutic targets for the prevention and treatment of kidney diseases.

Although high-protein diets continue to be popular for weight loss and type 2 diabetes, evidence suggests that worsening renal function may occur in individuals with-and perhaps without-impaired kidney function. High dietary protein intake can cause intraglomerular hypertension, which may result in kidney hyperfiltration, glomerular injury, and proteinuria. It is possible that long-term high protein intake may lead to de novo CKD. The quality of dietary protein may also play a role in kidney health. Compared with protein from plant sources, animal protein has been associated with an increased risk of ESKD in several observational studies, including the Singapore Chinese Health Study. Potential mediators of kidney damage from animal protein include dietary acid load, phosphate content, gut microbiome dysbiosis, and resultant inflammation. In light of such findings, adopting current dietary approaches that include a high proportion of protein for weight reduction or glycemic control should be considered with care in those at high risk for kidney disease. Given the possibility of residual confounding within some observational studies and the conflicting evidence from previous trials, long-term studies including those with large sample sizes are warranted to better ascertain the effects of high protein intake on kidney health., (Copyright © 2020 by the American Society of Nephrology.)

Background: Low physical performance in patients undergoing maintenance hemodialysis is associated with a high mortality rate. We investigated the clinical relevance of gait speed and handgrip strength, the two most commonly used methods of assessing physical performance., Methods: We obtained data regarding gait speed and handgrip strength from 277 hemodialysis patients and evaluated their relationships with baseline parameters, mental health, plasma inflammatory markers, and major adverse clinical outcomes. Low physical performance was defined by the recommendations suggested by the Asian Working Group on Sarcopenia., Results: The prevalence of low gait speed and handgrip strength was 28.2 and 44.8%, respectively. Old age, low serum albumin levels, high comorbidity index score, and impaired cognitive functions were associated with low physical performance. Patients with isolated low gait speed exhibited a general trend for worse quality of life than those with isolated low handgrip strength. Gait speed and handgrip strength showed very weak correlations with different determining factors (older age, the presence of diabetes, and lower serum albumin level for low gait speed, and lower body mass index and the presence of previous cardiovascular events for low handgrip strength). Patients with low gait speed and handgrip strength had elevated levels of plasma endocan and matrix metalloproteinase-7 and the highest risks for all-cause mortality and cardiovascular events among the groups (adjusted hazard ratio of 2.72, p = 0.024). Elderly patients with low gait speed and handgrip strength were at the highest risk for poor clinical outcomes., Conclusion: Gait speed and handgrip strength reflected distinctive aspects of patient characteristics and the use of both factors improved the prediction of adverse clinical outcomes in hemodialysis patients. Gait speed seems to be a better indicator of poor patient outcomes than is handgrip strength.

Background: Vascular calcification (VC) is a risk factor for cardiovascular disease in end-stage renal disease (ESRD) patients undergoing maintenance haemodialysis (MHD). However, evidence is still insufficient about the association between dialysis parameters and VC. Thus, this study was to evaluate association of dialysis parameters with VC., Methods: We enrolled 297 ESRD patients undergoing MHD at six distinct centers in Korea. Study participants were categorized into 3 groups by the scoring system of abdominal aortic calcification based on lateral lumbar radiography (no VC group: 0, mild VC group: 1-7 and advanced VC group: 8-24). We compared the features of dialysis parameters according to the severity of VC. Multivariate logistic regression analysis was used to calculate adjusted odd ratios (ORs) and 95% confidence interval (CI) for mild and advanced VC in each haemodialysis parameter (adjusted OR [95% CI])., Results: Pooled Kt/V (spKt/V), equilibrated Kt/V (eKt/V), standard Kt/V (stdKt/V) and the proportion of haemodiafiltration were increased along with the severity of VC. Multivariate regression analysis indicated that advanced VC was positively associated with spKt/V (5.27 [1.51-18.41]), eKt/V (6.16 [1.45-26.10]), stdKt/V (10.67 [1.74-65.52]) and haemodiafiltration (3.27 [1.74 to 6.16])., Conclusion: High dose dialysis and haemodiafiltration were significantly associated with advanced VC.