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Chronic kidney disease (CKD) is highly prevalent among elderly patients, and as the global population ages, the number of elderly patients with CKD is increasing. Elderly patients require additional considerations beyond those required for their younger counterparts, such as comorbidities, frailty, and geriatric syndromes. In this review, we primarily focus on these additional considerations specific to elderly patients and discuss the assessment of CKD and its management strategies, including blood pressure and glycemic control; dyslipidemia, anemia, and electrolyte and metabolic acidosis management; and medication dosage, among others, as well as polypharmacy and nonpharmacological management. Furthermore, the concept of conservative kidney management and the practical recommendations of the Korean Society of Geriatric Nephrology for elderly patients with end-stage kidney disease requiring dialysis therapy are discussed. In particular, the aging rate in Korea is exceptionally high; therefore, it is crucial to pay more attention to the increase in elderly patients with CKD. A more palliative approach, rather than intensive treatment strategies, may be necessary for these patients. In a world with an abundance of information, shared decision-making with patients is of great importance, and it is essential to keep in mind that this holds true for elderly patients as well., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2025.)

Objectives: The association between high-density lipoprotein (HDL) cholesterol levels and mortality in elderly patients undergoing hemodialysis is not well established. Thus, this study investigated HDL levels and mortality in elderly Korean patients undergoing hemodialysis., Methods: We recruited 1860 incident hemodialysis patients aged greater than 70 years from a retrospective cohort of the Korean Society of Geriatric Nephrology. The primary outcome measure was all-cause mortality., Results: The mean age of the cohort was 77.8 years, and 1049 (56.4%) were men. When we grouped the patients into HDL cholesterol tertiles, the T1 group (HDL level <30 mg/dL in men and <33 mg/dL in women) had a higher proportion of patients with end-stage kidney disease due to diabetic nephropathy. During the median follow-up period of 3.1 years, 1109 (59.7%) deaths occurred. In a multivariable Cox regression model, the T1 group had a significantly higher risk of mortality (hazard ratio [HR], 1.28; 95% confidence interval, 1.10-1.50; P = .002) compared to the T3 group. A nonlinear analysis using a restrictive spline curve showed that low HDL cholesterol levels were associated with increased HR when HDL cholesterol levels were <40 mg/dL; however, there was no association between HDL cholesterol and mortality when HDL cholesterol levels were >40 mg/dL. Triglyceride/HDL ratio was not significantly associated with the risk of mortality (HR per 1 log increase, 1.08; 95% confidence interval, 0.99-1.18; P = .069)., Conclusions: Low HDL cholesterol levels are associated with an increased risk of mortality in elderly patients undergoing hemodialysis. However, there was no significant relationship between HDL cholesterol levels and mortality when levels were below 40 mg/dL. Therefore, low HDL cholesterol levels may be a useful risk factor for predicting mortality in elderly patients undergoing hemodialysis., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

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: Endovascular therapy (EVT) has become the preferred treatment modality for femoropopliteal disease. However, there is limited evidence regarding its procedural and clinical outcomes according to the affected area., Aims: The aim of this study is to investigate clinical outcomes and device effectiveness according to treatment extent in the superficial femoral artery (SFA), popliteal artery (PA), or both., Methods: In this study, we analysed EVT for SFA (2,404 limbs), PA (155 limbs), SFA/PA (383 limbs) using the population in the K-VIS ELLA (Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Diseases) registry. The primary endpoint was target lesion revascularisation (TLR) at 2 years., Results: The SFA/PA group exhibited a higher prevalence of anatomical complexity, characterised by long lesions, moderate to severe calcification, and total occlusion. The procedures were successful in 97.2% of SFA, 92.9% of PA, and 95.6% of SFA/PA EVTs. The 2-year TLR rates were 21.1%, 18.6%, and 32.7% in the SFA, PA, and SFA/PA groups, respectively. SFA/PA EVT was associated with a significantly increased risk for TLR compared to the SFA group (adjusted hazard ratio [HR] 1.48 [1.09-2.00]; p=0.008) and a trend towards an increased risk compared to the PA group (adjusted HR 1.80 [1.00-3.27]; p=0.052). After overlap weighting, the use of a drug-coated balloon (DCB) was shown to be beneficial, with the lowest TLR rate after SFA and SFA/PA EVT., Conclusions: In this large real-world registry, SFA/PA EVT was associated with an increased risk for TLR at 2 years compared to the SFA or PA EVT groups, with favourable outcomes when using a DCB or drug-eluting stent in the SFA/PA EVT group.

Background: Since hemodialysis (HD) patients are prone to various complications and high mortality, they need to be treated in HD units with professional personnel, proper equipment, and facilities. The Korean Society of Nephrology has been conducting an HD unit accreditation program since 2016. This study was performed to evaluate whether a qualified dialysis center (QDC) reduced the mortality of HD patients., Methods: This longitudinal, observational cohort study included 31,227 HD from 832 facilities. HD units were classified into two groups: the hospitals that have been certified as QDC between 2016 and 2018 (n = 219) and hospitals that have never been certified as QDC (non-QDC, n = 613). Baseline characteristics and patient mortality were compared between QDC vs. non-QDC groups using Korean HD quality assessment data from 2018. Multivariate logistic regression and the Cox proportional hazards model were used to compare patient mortality between the two groups., Results: Among study subjects, 30.6% of patients were treated at QDC and 69.4% were treated at non-QDC. The patients in the QDC were younger and had a longer dialysis duration, lower serum phosphorus and calcium levels, and higher hemoglobin and single-pool Kt/V levels compared to the patients from the non-QDC group. After adjusting for demographic and clinical parameters, QCD independently reduced mortality risk (hazard ratio, 0.897; 95% confidence interval, 0.847-0.950; p < 0.001)., Conclusion: The HD unit accreditation program may reduce the risk of death among patients undergoing HD.

Introduction: Several studies have reported that pravastatin can mitigate the progression of kidney disease, but limited evidence exists regarding its effects on kidney function in Asian patients. This multicenter prospective observational study aimed to assess the effect of pravastatin on kidney function in Korean patients with dyslipidemia and type 2 diabetes mellitus (T2DM) in clinical practice., Methods: This 48-week prospective multicenter study included 2604 of 2997 eligible patients with dyslipidemia and T2DM who had available estimated glomerular filtration rate (eGFR) measurements. The primary endpoint was eGFR percent change at week 24 from baseline. We also assessed secondary endpoints, which included percent changes in eGFR at weeks 12 and 48 from baseline, as well as changes in eGFR, metabolic profiles (lipid and glycemic levels) at 12, 24, and 48 weeks from baseline, and safety., Results: We noted a significant improvement in eGFR, with mean percent changes of 2.5%, 2.5%, and 3.0% at 12, 24, and 48 weeks, respectively (all adjusted p < 0.05). The eGFR percent changes significantly increased in subgroups with baseline eGFR 30-90 mL/min/1.73 m 2 , glycated hemoglobin (HbA1c) ≥ 7 at baseline, no hypertension history, T2DM duration > 5 years, or previous statin therapy. Lipid profiles were improved and remained stable throughout the study, and interestingly, fasting glucose and HbA1c were improved at 24 weeks., Conclusion: Our findings suggest that pravastatin may have potential benefits for improving eGFR in Korean patients with dyslipidemia and T2DM. This could make it a preferable treatment option for patients with reduced kidney function., Trial Registration Number: NCT05107063 submitted October 27, 2021., (© 2024. The Author(s).)

Background: The reliability of presepsin as a biomarker of sepsis may be reduced in patients with acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT). This study analyzed the utility of plasma presepsin values in predicting mortality in patients with AKI requiring CKRT, particularly those with sepsis-associated AKI., Methods: This single-center retrospective study included 57 patients who underwent CKRT, with plasma presepsin measurements, from April 2022 to March 2023; 35 had sepsis-associated AKI. The predictive values of plasma presepsin, as well as Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, for 28-day mortality were analyzed using receiver operating characteristic curves. Multivariate Cox regression analysis was performed to identify risk factors for 28-day mortality in the sepsis-associated AKI subgroup., Results: Overall, plasma presepsin showed a lower area under the curve value (0.636; 95% confidence interval [CI], 0.491-0.781) than the APACHE II (0.663; 95% CI, 0.521-0.804) and SOFA (0.731; 95% CI, 0.599-0.863) scores did. However, in sepsis-associated AKI, the area under the curve increased to 0.799 (95% CI, 0.653-0.946), which was higher than that of the APACHE II (0.638; 95% CI, 0.450-0.826) and SOFA (0.697; 95% CI, 0.519-0.875) scores. In the multivariate Cox regression analysis, a high presepsin level was an independent risk factor for 28-day mortality in sepsis-associated AKI (hazard ratio, 3.437; p = 0.03)., Conclusion: Presepsin is a potential prognostic marker in patients with sepsis-associated AKI requiring CKRT.

Background: Intradialytic hypotension (IDH) is the primary complication of haemodialysis (HD); however, its diverse pathophysiology and inconsistent definitions complicate its prediction. Despite attempts using the heart rate variability (HRV) test for IDH prediction, studies on its usefulness for predicting IDH diagnosed per the nadir 90 criterion are lacking. We aimed to evaluate HRV test efficacy and reproducibility in predicting IDH based on the nadir 90 criterion., Methods: Seventy patients undergoing HD participated in this multicentre prospective observational study. The HRV test was performed during non-HD periods and IDH was monitored during 12 HD sessions. IDH was diagnosed according to the nadir 90 criterion, defined as a decrease in systolic blood pressure of ≤90 mmHg during HD. After monitoring, the HRV test was repeated. An HRV-IDH index was developed using multivariate logistic regression analysis employing HRV test parameters. The predictive power of the HRV-IDH index was analysed using the area under the receiver operating characteristics curve (AUROC). Reproducibility was evaluated using correlation analysis of two HRV tests on the same patient., Results: There were 37 and 33 patients in the IDH and non-IDH groups, respectively. The HRV-IDH index predicted IDH occurrence with AUROCs of 0.776 and 0.803 for patients who had experienced at least one or repeated IDH episodes, respectively. Spearman's correlation coefficient for HRV-IDH indices was 0.859 for the first and second HRV tests., Conclusions: The HRV test holds promise for predicting IDH, particularly for patients with recurring IDH diagnosed based on the nadir 90 criterion., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

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.

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).)

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: 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.)

Herein, we compared the association intensity of estimated glomerular filtration rate (eGFR) equations using creatinine (Cr) or cystatin C (CysC) with hyperphosphatemia and secondary hyperparathyroidism occurrence, which reflect the physiological changes occurring during chronic kidney disease (CKD) progression. This study included 639 patients treated between January 2019 and February 2022. The patients were divided into low- and high-difference groups based on the median value of the difference between the Cr-based eGFR (eGFR Cr ) and CysC-based eGFR (eGFR CysC ). Sociodemographic and laboratory factors underlying a high difference between eGFR Cr and eGFR CysC were analyzed. The association intensity of eGFR Cr , eGFR CysC and both Cr- and CysC-based eGFR (eGFR Cr-CysC ) was compared using the area under the receiver operating characteristic curve (AuROC) values for hyperphosphatemia and hyperparathyroidism occurrence in the overall cohort and the low- and high-difference groups. Age > 70 years and CKD grade 3 based on eGFR Cr were significant factors affecting the high differences. eGFR CysC and eGFR Cr-CysC showed higher AuROC values than that of eGFR Cr , especially in the high-difference group and in patients with CKD grade 3. Our results show that CysC should be evaluated in patients with significant factors, including age > 70 years and CKD grade 3, to accurately assess kidney function to better determine the physiological changes in CKD progression and predict prognosis accurately., (© 2023. The Author(s).)

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).)

Omega-3 fatty acids have been shown to be effective in lowering triglyceride (TG) levels; however, tolerability issues arise due to the large size of the pills. The purpose of this study was to examine the safety, compliance, and efficacy of Omethyl QTlet soft capsules (OQCs). This multi-center, prospective, observational study evaluated the safety, compliance, and efficacy of OQCs. Patients with hypertriglyceridemia with a history of omega-3 fatty acid intake were enrolled in this study and were prescribed OQCs (2 g−4 g/day) for eight weeks. All adverse events (AEs), adverse drug reactions (ADRs), and serious adverse events (SAEs) were recorded for safety evaluation. Adherence to treatment was assessed using questionnaires, and efficacy was assessed by changes in lipid and lipoprotein levels after eight weeks from baseline. The convenience of taking medication was analyzed for 580 patients, and the efficacy test was performed for 563 patients. The AE and ADR rates were 8.2% and 5.7%, respectively. There were only two SAEs. Of the patients, 55.8% responded that the OQC improved medication convenience, and mean changes in TG, total cholesterol, LDL-C, and non-HDL-C from baseline to eight weeks were −37.88 mg/dL, −11.56 mg/dL, −5.55 mg/dL, and −10.87 mg/dL, respectively (p-values < 0.001). In patients who had previously taken omega-3 fatty acids, OQCs showed safety and efficacy in lowering TG, and it was confirmed that compliance with medicine also improved compared to omega-3 fatty acids.

Introduction: Tacrolimus (TAC) has been widely used as an immunosuppressant after kidney transplantation (KT); however, the combined effects of intra-patient variability (IPV) and inter-patient variability of TAC-trough level (C0) in blood remain controversial. This study aimed to determine the combined impact of TAC-IPV and TAC inter-patient variability on allograft outcomes of KT., Methods: In total, 1,080 immunologically low-risk patients who were not sensitized to donor human leukocyte antigen (HLA) were enrolled. TAC-IPV was calculated using the time-weighted coefficient variation (TWCV) of TAC-C0, and values > 30% were classified as high IPV. Concentration-to-dose ratio (CDR) was used for calculating TAC inter-patient variability, and CDR < 1.05 ng•mg/mL was classified as rapid metabolizers (RM). TWCV was calculated based on TAC-C0 up to 1 year after KT, and CDR was calculated based on TAC-C0 up to 3 months after KT. Patients were classified into four groups according to TWCV and CDR: low IPV/non-rapid metabolizer (NRM), high IPV/NRM, low IPV/RM, and high IPV/RM. Subgroup analysis was performed for pre-transplant panel reactive antibody (PRA)-positive and -negative patients (presence or absence of non-donor-specific HLA-antibodies). Allograft outcomes, including deathcensored graft loss (DCGL) and biopsy-proven allograft rejection (BPAR), were compared., Results: The incidences of DCGL, BPAR, and overall graft loss were the highest in the high-IPV/RM group. In addition, a high IPV/RM was identified as an independent risk factor for DCGL. The hazard ratio of high IPV/RM for DCGL and the incidence of active antibody-mediated rejection were considerably increased in the PRA-positive subgroup., Discussion: High IPV combined with RM (inter-patient variability) was closely related to adverse allograft outcomes, and hence, more attention must be given to pre-transplant PRA-positive patients., 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 Park, Lee, Eum, Ko, Min, Yoon, Hwang, Yun, Yang, Shin and Chung.)

Background: Fabry disease (FD) is a lysosome storage disease (LSD) characterized by significantly reduced intracellular autophagy function. This contributes to the progression of intracellular pathologic signaling and can lead to organ injury. Phospholipid-polyethyleneglycol-capped Ceria-Zirconia antioxidant nanoparticles (PEG-CZNPs) have been reported to enhance autophagy flux. We analyzed whether they suppress globotriaosylceramide (Gb3) accumulation by enhancing autophagy flux and thereby attenuate kidney injury in both cellular and animal models of FD., Results: Gb3 was significantly increased in cultured human renal proximal tubular epithelial cells (HK-2) and human podocytes following the siRNA silencing of α galactosidase A (α-GLA). PEG-CZNPs effectively reduced the intracellular accumulation of Gb3 in both cell models of FD and improved both intracellular inflammation and apoptosis in the HK-2 cell model of FD. Moreover these particles attenuated pro fibrotic cytokines in the human podocyte model of FD. This effect was revealed through an improvement of the intracellular autophagy flux function and a reduction in reactive oxygen species (ROS). An FD animal model was generated in which 4-week-old male B6;129-Gla tm1Kul /J mice were treated for 8 weeks with 10 mg/kg of PEG-CZNPs (twice weekly via intraperitoneal injection). Gb3 levels were reduced in the kidney tissues of these animals, and their podocyte characteristics and autophagy flux functions were preserved., Conclusions: PEG-CZNPs alleviate FD associated kidney injury by enhancing autophagy function and thus provide a foundation for the development of new drugs to treat of storage disease., (© 2022. The Author(s).)

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.

Background: Detergent poisoning mostly occurs through oral ingestion (> 85%), ocular exposure (< 15%), or dermal exposure (< 8%). Reports of detergent poisoning through an intravenous injection are extremely rare. In addition, there are very few cases of renal toxicity directly caused by detergents. Here, we report a unique case of acute kidney injury caused by detergent poisoning through an accidental intravenous injection., Case Summary: A 61-year-old man was intravenously injected with 20 mL of detergent by another patient in the same room of a local hospital. The surfactant and calcium carbonate accounted for the largest proportion of the detergent. The patient complained of vascular pain, chest discomfort, and nausea, and was transferred to our institution. After hospitalization, the patient's serum creatinine level increased to 5.42 mg/dL, and his daily urine output decreased to approximately 300 mL. Renal biopsy findings noted that the glomeruli were relatively intact; however, diffuse acute tubular injury was observed. Generalized edema was also noted, and the patient underwent a total of four hemodiafiltration sessions. Afterward, the patient's urine output gradually increased whereas the serum creatinine level decreased. The patient was discharged in a stable status without any sequelae., Conclusion: Detergents appear to directly cause renal tubular injury by systemic absorption. In treating a patient with detergent poisoning, physicians should be aware that the renal function may also deteriorate. In addition, timely renal replacement therapy may help improve the patient's prognosis., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Compared with conventional bilateral femoral (BF) approach, radial plus ipsilateral femoral (RF) approach may be feasible in the percutaneous intervention for iliac artery chronic total occlusion (CTO)., Methods: We included patients who underwent iliac CTO intervention between August 2009 and July 2018 in a tertiary referral center in Korea., Results: A total of 83 patients were enrolled in this study. Of them, 51 and 32 patients were categorized into RF and BF initial access groups, respectively. The overall success rates were 98.0% and 96.7% in RF and BF group, respectively, and the techniques were also similar including use of bilateral wiring, stent type and profile, and post balloon but longer procedure time in the BF group. Additional contralateral femoral access was needed in 6 patients for the treatment of contralateral lesions, distal embolization, and due to tortuous right subclavian artery. Periprocedural complications including vascular injury, iliac perforation, and distal embolization occurred similarly in both groups with numerically lower rate of periprocedural bleeding in the RF group (9.8%) than in the BF group (21.9%). Clinical follow-up at 6 months showed there were no difference in the rates of death, cardiovascular death, target-limb reintervention, and unplanned target limb amputation in both groups., Conclusions: RF approach for iliac CTO intervention was related to similar technical success rate with acceptable periprocedural safety outcomes compared with conventional BF approach., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Sodium-glucose cotransporter 2 inhibitors reduce the risk of cardiovascular death in individuals with type 2 diabetes mellitus (T2DM) and cardiovascular disease, but the effect of these inhibitors on early cardiovascular disease remains unknown. This study evaluated the effect of dapagliflozin on the metabolic profiles and endothelial cell function in obese patients with T2DM without established cardiovascular disease., Methods: We enrolled 140 patients with a mean age, weight, and body mass index (BMI) of 47 years, 83 kg, and 30.3 kg/m 2 , respectively. Dapagliflozin (10 mg daily for 6 months) was administered to obese patients with T2DM without established cardiovascular disease. Participants' weight, BMI, body fat mass (BFM), muscle mass, glycosylated hemoglobin (HbA1c), lipid profile, waist to hip ratio (WHR), and pulse wave velocity (PWV) were measured at baseline and after 6 months., Results: Participants experienced statistically significant reductions in their HbA1c, fasting plasma glucose, low-density lipoprotein cholesterol, total cholesterol, body weight, BMI, WHR, BFM, and aortic PWV, without a significant change in their muscle mass, extracellular fluid, or intracellular volume. Statistically significant reductions in aortic PWV were associated with a decrease in BFM, visceral fat, WHR, and homeostatic model assessment of insulin resistance., Conclusion: Dapagliflozin may be beneficial in preventing early cardiovascular disease in obese patients with T2DM without established cardiovascular disease.

Oxidative stress is one of the principal causes of hypoxia-induced kidney injury. The ceria nanoparticle (CNP) is known to exhibit free radical scavenger and catalytic activities. When zirconia is attached to CNPs (CZNPs), the ceria atom tends to remain in a Ce 3+ form and its efficacy as a free radical scavenger thus increases. We determined the effectiveness of CNP and CZNP antioxidant activities against hypoxia-induced acute kidney injury (AKI) and observed that these nanoparticles suppress the apoptosis of hypoxic HK-2 cells by restoring autophagy flux and alleviating mitochondrial damage. In vivo experiments revealed that CZNPs effectively attenuate hypoxia-induced AKI by preserving renal structures and glomerulus function. These nanoparticles can successfully diffuse into HK-2 cells and effectively counteract reactive oxygen species (ROS) to block hypoxia-induced AKI. This suggests that these particles represent a novel approach to controlling this condition.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Crosstalk between liver and skeletal muscle is vital for glucose homeostasis. Hepatokines, liver-derived proteins that play an important role in regulating muscle metabolism, are important to this communication. Here we identify apolipoprotein J (ApoJ) as a novel hepatokine targeting muscle glucose metabolism and insulin sensitivity through a low-density lipoprotein receptor-related protein-2 (LRP2)-dependent mechanism, coupled with the insulin receptor (IR) signaling cascade. In muscle, LRP2 is necessary for insulin-dependent IR internalization, an initial trigger for insulin signaling, that is crucial in regulating downstream signaling and glucose uptake. Of physiologic significance, deletion of hepatic ApoJ or muscle LRP2 causes insulin resistance and glucose intolerance. In patients with polycystic ovary syndrome and insulin resistance, pioglitazone-induced improvement of insulin action is associated with an increase in muscle ApoJ and LRP2 expression. Thus, the ApoJ-LRP2 axis is a novel endocrine circuit that is central to the maintenance of normal glucose homeostasis and insulin sensitivity.

Background: Chronic exposure to elevated levels of free fatty acids contributes to pancreatic β-cell dysfunction. Although it is well known that metformin induces cellular energy depletion and a concomitant activation of AMP-activated protein kinase (AMPK) through inhibition of the respiratory chain, previous studies have shown inconsistent results with regard to the action of metformin on pancreatic β-cells. We therefore examined the effects of metformin on pancreatic β-cells under lipotoxic stress., Methods: NIT-1 cells and mouse islets were exposed to palmitate and treated with 0.05 and 0.5 mM metformin. Cell viability, glucose-stimulated insulin secretion, cellular adenosine triphosphate, reactive oxygen species (ROS) levels and Rho kinase (ROCK) activities were measured. The phosphorylation of AMPK was evaluated by Western blot analysis and mRNA levels of endoplasmic reticulum (ER) stress markers and NADPH oxidase (NOX) were measured by real-time quantitative polymerase chain reaction analysis., Results: We found that metformin has protective effects on palmitate-induced β-cell dysfunction. Metformin at a concentration of 0.05 mM inhibits NOX and suppresses the palmitate-induced elevation of ER stress markers and ROS levels in a AMPK-independent manner, whereas 0.5 mM metformin inhibits ROCK activity and activates AMPK., Conclusion: This study suggests that the action of metformin on β-cell lipotoxicity was implemented by different molecular pathways depending on its concentration. Metformin at a usual therapeutic dose is supposed to alleviate lipotoxic β-cell dysfunction through inhibition of oxidative stress and ER stress., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019 Korean Diabetes Association.)

BACKGROUND Hypernatremia is associated with poor outcomes in critically ill patients, and an accurate assessment of water volume is important to determine appropriate fluid hydration. Bioelectrical impedance analysis (BIA) is a new, noninvasive, and relatively easy method for measuring hydration status. This study aimed to investigate whether bioelectrical impedance measurements of body water could reduce the frequency of blood sampling for fluid replacement in patients with hypernatremia. MATERIAL AND METHODS Fifty-one hospitalized patients were studied with hypernatremia, defined as a serum sodium ≥150 mmol/L determined by laboratory testing. Laboratory and BIA measurements were compared, and water deficiency was calculated with a conventional formula (sodium-corrected Watson formula) and measured by BIA. RESULTS The value of the absolute fluid overload (AFO) equivalent to the overhydration (OH) value, determined using BIA, did not accurately represent water deficit in patients with hypernatremia (r=0.137, P=0.347). Although the total body water (TBW) measured by BIA showed a significant correlation with that determined by the conventional formula (r=0.861, P<0.001), there was a proportional bias (r=0.617, P<0.001). The intracellular water (ICW) measured by BIA underestimated the TBW level calculated by the conventional formula by about 14.06±4.0 L in the Bland-Altman analysis. CONCLUSIONS It is not currently possible to replace blood testing with BIA for assessing volume status in hypernatremic patients. However, ICW value measured by BIA might represent plasma sodium level more accurately than extracellular water (ECW) or TBW value in patients with hypernatremia.

Hypoxia is an important cause of acute kidney injury (AKI) in various conditions because kidneys are one of the most susceptible organs to hypoxia. In this study, we investigated whether nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidase 4 (Nox4) plays a role in hypoxia induced AKI in a cellular and animal model. Expression of Nox4 in cultured human renal proximal tubular epithelial cells (HK-2) was significantly increased by hypoxic stimulation. TGF-β1 was endogenously secreted by hypoxic HK-2 cells. SB4315432 (a TGF-β1 receptor I inhibitor) significantly inhibited Nox4 expression in HK-2 cells through the Smad-dependent cell signaling pathway. Silencing of Nox4 using Nox4 siRNA and pharmacologic inhibition with GKT137831 (a specific Nox1/4 inhibitor) reduced the production of ROS and attenuated the apoptotic pathway. In addition, knockdown of Nox4 increased cell survival in hypoxic HK-2 cells and pretreatment with GKT137831 reproduce these results. This study demonstrates that hypoxia induces HK-2 cell apoptosis through a signaling pathway involving TGF-β1 via Smad pathway induction of Nox4-dependent ROS generation. In an ischemia/reperfusion rat model, pretreatment of GKT137831 attenuated ischemia/reperfusion induced acute kidney injury as indicated by preserved kidney function, attenuated renal structural damage and reduced apoptotic cells. Therapies targeting Nox4 may be effective against hypoxia-induced AKI., Competing Interests: The authors have declared that no competing interests exist.

A novel Gram-stain-negative, aerobic, motile by means of gliding, and short rod-shaped bacterium, designated strain SH35 T , was isolated from the dry surface of a tidal flat in Hwasung-si, South Korea. Growth occurred at 10-40°C (optimum 30°C), at pH 6.0-8.0 (optimum pH 7.0), in 1-12% NaCl (optimum 2%), and was inhibited in the absence of NaCl and Ca 2+ ions. Phylogenetic analysis based on the 16S rRNA gene sequences showed that strain SH35 T belonged to the genus Gramella and was a member of the family Flavobacteriaceae with highest sequence similarity to Gramella flava JLT2011 T (96.1%), followed by Gramella oceani CCAMSZ-TT (95.6%), and 93.0-94.9% to other recognized Gramella species. The major cellular fatty acids (> 5% of the total) of strain SH35T were iso-C 15:0 , Iso-C 16:0 , anteiso-C 15:0 , iso-C 17:0 3-OH and summed feature 9 (C16:0 10-methyl and/or C 17:1 iso ω9с). The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids and nine unidentified polar lipids. The major respiratory quinone and the predominant polyamine were menaquinone-6 (MK-6) and symhomospermidine, respectively. The DNA G + C content was 40.5 mol% (39.7% based on total genome calculations). Based on phylogenetic analysis and physiological and biochemical characterization, strain SH35 T represents a novel species of the genus Gramella, for which the name Gramella fulva sp. nov. is proposed. The type strain is SH35 T (= KACC 19447 T = JCM 32369 T ).

Obesity is a major risk factor for developing nonalcoholic fatty liver disease (NAFLD). NAFLD is the most common form of chronic liver disease and is closely associated with insulin resistance, ultimately leading to cirrhosis and hepatocellular carcinoma. However, knowledge of the intracellular regulators of obesity-linked fatty liver disease remains incomplete. Here we showed that hepatic Rho-kinase 1 (ROCK1) drives obesity-induced steatosis in mice through stimulation of de novo lipogenesis. Mice lacking ROCK1 in the liver were resistant to diet-induced obesity owing to increased energy expenditure and thermogenic gene expression. Constitutive expression of hepatic ROCK1 was sufficient to promote adiposity, insulin resistance, and hepatic lipid accumulation in mice fed a high-fat diet. Correspondingly, liver-specific ROCK1 deletion prevented the development of severe hepatic steatosis and reduced hyperglycemia in obese diabetic (ob/ob) mice. Of pathophysiological significance, hepatic ROCK1 was markedly upregulated in humans with fatty liver disease and correlated with risk factors clustering around NAFLD and insulin resistance. Mechanistically, we found that hepatic ROCK1 suppresses AMPK activity and a ROCK1/AMPK pathway is necessary to mediate cannabinoid-induced lipogenesis in the liver. Furthermore, treatment with metformin, the most widely used antidiabetes drug, reduced hepatic lipid accumulation by inactivating ROCK1, resulting in activation of AMPK downstream signaling. Taken together, our findings establish a ROCK1/AMPK signaling axis that regulates de novo lipogenesis, providing a unique target for treating obesity-related metabolic disorders such as NAFLD.

Two strains of Gram-stain-positive, endospore-forming, motile by means of peritrichous flagella, aerobic or facultative anaerobic, and rod-shaped bacteria that were designated ON8 T and ON6 T were isolated from soil collected from a mountain wetland in Gwang-ju, Republic of Korea. The isolates were catalase-positive and oxidase-negative. Cells of ON8 T and ON6 T grew at 15-35 °C (optimal 30 °C) and 15-40 °C (optimal 30 °C), respectively. The major menaquinone was MK-7 and the major cellular fatty acids (>10 % of the total) were anteiso-C15 : 0, iso-C15 : 0, C14 : 0 and C16 : 0. The predominant polar lipids were diphosphatidylglycerol, aminophospholipid and phospholipid. Meso-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The DNA G+C contents of strains ON8 T and ON6 T were 50.6 and 53.5 mol%, respectively, and the 16S rRNA gene sequence analysis showed that the nearest phylogenetic neighbour of both strains was Gorillibacterium massiliense G5 T (93.9 %), followed by the members of the genus Paenibacillus in the family Paenibacillaceae. The DNA-DNA hybridization relatedness value between ON8 T and ON6 T was 44.1 %, which indicated that they represented distinct species. Based on polyphasic characteristics, a novel genus is proposed with the name Paludirhabdus gen. nov., which consists of two species, Paludirhabdus telluriireducens sp. nov. (the type species; type strain ON8 T =KACC 19267 T =JCM 31958 T ) and Paludirhabdus pumila sp. nov. (type strain ON6 T =KACC 19266 T =JCM 31957 T ).

Background: Amyloidosis is a very rare disease that is difficult to diagnose because of the unspecific early clinical manifestations of the disease. Accurate and early diagnosis is extremely important because the effect of treatment is dependent on the extent of disease progression. Sicca syndrome and nail dystrophy are very rare symptoms of amyloidosis. We report here a case of sicca syndrome and nail dystrophy with renal dysfunction in a 52-year-old Korean woman who was diagnosed as having systemic amyloidosis., Case Presentation: We present the case of a 52-year-old Korean woman complaining of dry mouth and nail dystrophy for 4 months as an initial symptom. A slit lamp examination revealed superficial keratoconjunctival erosion in both eyes. A laboratory test showed anemia, azotemia, and proteinuria. Urine protein electrophoresis showed increased gamma globulin excretion. Serum free light chain of kappa and lambda were increased. Histopathological studies of biopsy specimens of minor salivary glands and kidney revealed deposits of amyloid fibrils. A bone marrow aspiration biopsy showed hypercellular marrow with 5% plasma cells. She was diagnosed as having primary systemic amyloidosis then started on chemotherapy., Conclusion: Such atypical mucocutaneous manifestations of amyloidosis can serve as important early diagnostic signs with less invasive biopsy confirmation in patients with systemic amyloidosis.

A novel Gram-stain-negative, motile by means of gliding, and short rod-shaped bacterium, designated HS916T, was isolated from soil polluted by sewer water in Cheonan-si, South Korea. Growth occurred at 10-35°C (optimum 30°C), pH 6.0-8.0 (optimum pH 7.0), and 0-1% sodium chloride (NaCl, w/v). Based on similarities of 16S rRNA gene sequences, strain HS916 T was closely related to members of the genus Flavobacterium, exhibiting the highest sequence similarities with Flavobacterium glycines Gm-149 T (96.4%), followed by F. granuli Kw05 T (96.3%), F. fluminis 3R17 T (96.3%), F. aquicola TMd3a3 T (96.2%), and F. nitratireducens N1 T (96.2%). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain HS916T was placed in a monophyletic cluster with F. nitratireducens N1 T and F. fluminis 3R17 T . The predominant fatty acids (> 5% of the total) of strain HS916 T were iso-C 15:0 , anteiso-C 15:0 , iso-C 15:0 3-OH, C 17:1 ω6с, C 16:0 3-OH, iso-C 17:0 3-OH, and summed feature 3 (C 16:1 ω7с and/or C 16:1 ω6с). The major polar lipids of the strain comprised phosphatidylethanolamine, unidentified aminolipids, and five unidentified lipids. The predominant respiratory quinone and the major polyamine were menaquinone-6 (MK-6) and symhomospermidine, respectively. The DNA G + C content of strain HS916 T was 34.9 mol%. Based on polyphasic analyses, strain HS916 T represents a novel species belonging to the genus Flavobacterium, for which the name Flavobacterium parvum sp. nov. is proposed. The type strain is HS916T (= KACC 19448 T = JCM 32368 T ).

A bacterial strain, designated D13 T , was isolated from sandy soil near a stream in Sinan-gun, Republic of Korea. Cells were Gram-stain-negative, aerobic, non-motile and flexible rod-shaped. Growth occurred at 15-35 °C (optimum 30 °C) and pH 6.5-8.0 (pH 7.0). NaCl was not obligatory for growth but could be tolerated at up to 0.5 % (w/v) NaCl. The DNA G+C content of the genomic DNA of strain D13 T was 57.7 mol% and a phylogenetic analysis of the 16S rRNA gene sequence revealed that strain D13 T formed a distinct evolutionary lineage within the family Rhodanobacteraceae of the order Lysobacterales. Strain D13 T showed highest 16S rRNA sequence similarity to Lysobacter hankyongensis KTCe-2 T (92.7 %), followed by Luteimonas cucumeris Y4 T (92.7 %), Dyella japonica XD53 T (92.6 %) and Aquimonas voraii GPTSA 20 T (92.5 %). The major cellular fatty acids (>10 % of the total) were iso-C16 : 0, iso-C15 : 0 and summed feature 9 (iso-C17 : 1ω9с and/or C16 : 0 10-methyl). The respiratory quinone was ubiquinone-8 and the major polar lipids of the isolate consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and phosphatidylmonomethylethanolamine. Based on polyphasic analysis, strain D13 T could be differentiated from other genera in the family Rhodanobacteraceae, which suggests that strain D13 T represents a novel species of a new genus in the family Rhodanobacteraceae, for which the name Ahniella affigens gen. nov., sp. nov. is proposed. The type strain is D13 T (=KACC 19270 T =JCM 31634 T ).

The Korean Association of Medical Colleges (KAMC) developed graduate outcomes based on "The role of Korean doctor, 2014" to serve as guidelines regarding outcome-based education in Korea. The working group in this study analyzed 65 competencies proposed in "The role of Korean doctor, 2014" according to the developmental principle that certain outcomes should be demonstrated at the point of entry into the graduate medical education. We established 34 competencies as "preliminary graduate outcomes" (PGOs). The advisory committee consisted of 11 professors, who reviewed the validity of PGOs. Ultimately, a total of 19 "revised graduate outcomes" (RGOs) were selected. We modified the RGOs based on opinions from medical schools and a public hearing. In November 2017, the KAMC announced the "graduate outcomes for basic medical education," which serves as a guide for basic medical education for the 40 medical schools throughout Korea. Medical schools can expand the graduate outcomes according to their educational goals and modify them according to their own context. We believe that graduate outcomes can be a starting point for connecting basic medical education to graduate medical education.

Ischemia-reperfusion injury (IRI) may cause acute kidney disease (AKD) by mediating the oxidative stress-induced apoptosis of parenchymal cells. The extract of Rhus verniciflua Stokes (RVS) is used as a traditional herbal medicine as it exhibits anti-oxidant, anti-apoptotic and anti-inflammatory properties. Therefore, the current study investigated the therapeutic effect and the underlying mechanism of RVS on IRI-induced AKD in vivo and in vitro . The current study assessed the effects of RVS on a mouse model of renal IRI and in hypoxic human renal tubular epithelial HK-2 cells. The results demonstrated that the IRI-induced elevation of blood urea nitrogen, serum creatinine and lactate dehydrogenase was significantly attenuated by the intraoral administration of RVS (20 mg/kg/day) for 14 days prior to surgery. It was demonstrated that IRI surgery induced histological damage and cellular apoptosis in renal parenchyma, which were attenuated by pretreatment with RVS. Furthermore, in HK-2 cells incubated with 300 µM CoCl 2 to induce chemical hypoxia, it was demonstrated that RVS treatment significantly inhibited cell death and the production of reactive oxygen species (ROS). Furthermore, RVS treatment upregulated the levels of endogenous antioxidant enzymes, including heme oxygenase-1 and catalase, as well as their upstream regulator nuclear factor erythroid 2-related factor 2, in HK-2 cells. Taken together, these results suggested that the intraoral administration of RVS induces a therapeutic effect on IRI-induced AKD. These effects are at least partly due to the attenuation of ROS production via upregulation of the antioxidant defense system in renal tubular cells.

Background: Colistin (polymyxin E) is an important constituent of the polymyxin class of cationic polypeptide antibiotics. Intrarenal oxidative stress can contribute to colistin-induced nephrotoxicity. Nicotinamide adenine dinucleotide 3-phosphate oxidases (Noxs) are important sources of reactive oxygen species. Among the various types of Noxs, Nox4 is predominantly expressed in the kidney., Objectives: We investigated the role of Nox4 and benefit of Nox4 inhibition in colistin-induced acute kidney injury using in vivo and in vitro models., Methods: Human proximal tubular epithelial (HK-2) cells were treated with colistin with or without NOX4 knockdown, or GKT137831 (most specific Nox1/4 inhibitor). Effects of Nox4 inhibition on colistin-induced acute kidney injury model in Sprague-Dawley rats were examined., Results: Nox4 expression in HK-2 cells significantly increased following colistin exposure. SB4315432 (transforming growth factor-β1 receptor I inhibitor) significantly inhibited Nox4 expression in HK-2 cells. Knockdown of NOX4 transcription reduced reactive oxygen species production, lowered the levels of pro-inflammatory markers (notably mitogen-activated protein kinases) implicated in colistin-induced nephrotoxicity and attenuated apoptosis by altering Bax and caspase 3/7 activity. Pretreatment with GKT137831 replicated these effects mediated by downregulation of mitogen-activated protein kinase activities. In a rat colistin-induced acute kidney injury model, administration of GKT137831 resulted in attenuated colistin-induced acute kidney injury as indicated by attenuated impairment of glomerulus function, preserved renal structures, reduced expression of 8-hydroxyguanosine and fewer apoptotic cells., Conclusions: Collectively, these findings identify Nox4 as a key source of reactive oxygen species responsible for kidney injury in colistin-induced nephrotoxicity and highlight a novel potential way to treat drug-related nephrotoxicity.

Strain M1-21 T is a Gram-stain-negative, strictly aerobic and short-rod-shaped bacterium, motile by means of a single polar flagellum; it was isolated from freshwater sediment in Korea. It grew at 10-40 °C (optimum 25 °C), pH 6.0-8.0 (optimum pH 7.0) and with 0-0.75 % (w/v) NaCl (optimal growth occurred in the absence of NaCl) on R2A agar, and it accumulated poly-β-hydroxybutyrate granules inside the cells. According to 16S rRNA gene sequence analysis, strain M1-21 T showed highest sequence similarity with Uliginosibacterium gangwonense (94.7 %) and Uliginosibacterium paludis (94.4 %). Phylogenetic analysis of the 16S rRNA gene sequences revealed that strain M1-21 T belongs to the genus Uliginosibacterium. The DNA G+C content of strain M1-21 T was 61.9 mol%. The predominant respiratory quinone was ubiquinone-8. The major fatty acids (>10 % of the total) were C16 : 0 and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c), and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Strain M1-21 T showed distinct phenotypic characteristics that differentiated it from species of the genus Uliginosibacterium. Based on these results, strain M1-21 T represents a novel species of the genus Uliginosibacterium, for which the name Uliginosibacterium sediminicola sp. nov. is proposed. The type strain is M1-21 T (=KACC 19271 T =JCM 32000 T ).

An aerobic, Gram-negative, motile by means of a single polar flagellum, and ovoid-shaped bacterium, designated D3 T , was isolated from shallow stream sediments in Sinan-gun, South Korea. Growth occurred at 15-40 °C (optimum 35 °C), at pH 7.0-8.0 (optimum pH 7.0), and at an optimum NaCl concentration of 0.5 % (w/v). The major cellular fatty acids (>7 % of the total) were C16 : 0, C18 : 0 2-OH, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The predominant quinone was ubiquinone-10, and the G+C content of the genomic DNA of strain D3 T was 73.1 mol%. The major polyamine was spermidine. The major polar lipids of the isolate were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine and phosphatidylglycerol. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain D3 T clustered with Roseomonas aquatica TR53 T within the genus Roseomonas. The 16S rRNA gene sequence of strain D3 T showed the highest sequence similarity to R. aquatica TR53 T (95.9 %), followed by Roseomonas rosea 173-96 T (95.7 %) and Roseomonas aerilata 5420S-30 T (95.0 %). Based on the phenotypic, phylogenetic and chemotaxonomic characterization, strain D3 T represents a novel species of the genus Roseomonas, for which the name Roseomonas fluminis sp. nov. is proposed. The type strain is D3 T (=KACC 19269 T =JCM 31968 T ).

Contrast-induced acute kidney injury (CIAKI) is a leading cause of acute kidney injury following radiographic procedures. Intrarenal oxidative stress plays a critical role in CIAKI. Nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidases (Noxs) are important sources of reactive oxygen species (ROS). Among the various types of Noxs, Nox4 is expressed predominantly in the kidney in rodents. Here, we evaluated the role of Nox4 and benefit of Nox4 inhibition on CIAKI using in vivo and in vitro models. HK-2 cells were treated with iohexol, with or without Nox4 knockdown, or the most specific Nox1/4 inhibitor (GKT137831). Effects of Nox4 inhibition on CIAKI mice were examined. Expression of Nox4 in HK-2 cells was significantly increased following iohexol exposure. Silencing of Nox4 rescued the production of ROS, downregulated pro-inflammatory markers (particularly phospho-p38) implicated in CIAKI, and reduced Bax and caspase 3/7 activity, which resulted in increased cellular survival in iohexol-treated HK-2 cells. Pretreatment with GKT137831 replicated these effects by decreasing levels of phospho-p38. In a CIAKI mouse model, even though the improvement of plasma blood urea nitrogen was unclear, pretreatment with GKT137831 resulted in preserved structure, reduced expression of 8-hydroxy-2'-deoxyguanosine (8OHdG) and kidney injury molecule-1 (KIM-1), and reduced number of TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)-positive cells. These results suggest Nox4 as a key source of reactive oxygen species responsible for CIAKI and provide a novel potential option for prevention of CIAKI.

Objective: Insulin resistance is a major risk factor for type 2 diabetes. ApolipoproteinJ (ApoJ) has been implicated in altered pathophysiologic states including cardiovascular and Alzheimer's disease. However, the function of ApoJ in regulation of glucose homeostasis remains unclear. This study sought to determine whether serum ApoJ levels are associated with insulin resistance in human subjects and if they change after interventions that improve insulin sensitivity., Methods: Serum ApoJ levels and insulin resistance status were assessed in nondiabetic (ND) and type 2 diabetic (T2D) subjects. The impacts of rosiglitazone or metformin therapy on serum ApoJ levels and glucose disposal rate (GDR) during a hyperinsulinemic/euglycemic clamp were evaluated in a separate cohort of T2D subjects. Total ApoJ protein or that associated with the HDL and LDL fractions was measured by immunoblotting or ELISA., Results: Fasting serum ApoJ levels were greatly elevated in T2D subjects (ND vs T2D; 100±8.3 vs. 150.6±8.5AU, P<0.0001). Circulating ApoJ levels strongly correlated with fasting glucose, fasting insulin, HOMA-IR, and BMI. ApoJ levels were significantly and independently associated with HOMA-IR, even after adjustment for age, sex, and BMI. Rosiglitazone treatment in T2D subjects resulted in a reduction in serum ApoJ levels (before vs. after treatment; 100±13.9 vs. 77±15.2AU, P=0.015), whereas metformin had no effect on ApoJ levels. The change in ApoJ levels during treatment was inversely associated with the change in GDR. Interestingly, ApoJ content in the LDL fraction was inversely associated with HOMA-IR., Conclusion: Serum ApoJ levels are closely correlated with the magnitude of insulin resistance regardless of obesity, and decrease along with improvement of insulin resistance in response only to rosiglitazone in type 2 diabetes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A novel Gram-stain-negative, aerobic, non-motile and short-rod-shaped bacterium, designated RP18T, was isolated from forest soil in Gwang-ju, Republic of Korea. Growth occurred at 15-30 °C (optimum 30 °C), pH 6.0-7.0 (optimum pH 7.0), and was inhibited in the presence of normal saline. According to the 16S rRNA gene sequence, strain RP18T showed the highest sequence similarity to Sphingomonas kyeonggiensis THG-DT81T (96.0 %), followed by Sphingomonas pituitosa EDIVT (95.4 %) and Sphingomonas dokdonensis DS-4T (95.2 %). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain RP18T was clustered with Sphingomonas gimensis 9PNM-6T and Sphingomonas jejuensis MS-31T under the genus Sphingomonas. The G+C content of the genomic DNA of strain RP18T was 61.5 mol%. The major cellular fatty acids (>6 % of the total) were C16 : 0, C14 : 0 2-OH, C17 : 1ω6с, summed feature 3 (C16 : 1ω7с and/or C16 : 1ω6с) and summed feature 8 (C18 : 1ω7с and/or C18 : 1ω6с). Ubiquinone-10 (Q-10) and sym-homospermidine were detected as the predominant respiratory quinone and major compound in the polyamine pattern, respectively. The major polar lipids of the isolate consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phospholipid and sphingoglycolipid. Based on phylogenetic analysis and physiological and biochemical characterization, strain RP18T represents a novel species of the genus Sphingomonas, for which the name Sphingomonas silvisoli sp. nov. is proposed. The type strain is RP18T (=KACC 18914T=JCM 31801T).

Receptors for glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are present in vascular endothelial cells. Previous studies investigating euglycemic status have demonstrated that GIP is directly involved in the physiology of blood vessels by controlling the blood flow rate of portal veins and that GLP-1 has a protective effect on blood vessels by acting on endothelial cells. However, to the best of our knowledge, the effects of GIP and GLP-1 on endothelial cells in patients with hyperglycemia remain unknown. Therefore, the present study investigated whether the effect of the incretin hormones GLP-1 and GIP differed with regards to the reversal of endothelial cell dysfunction caused by hyperglycemia. The production of nitric oxide (NO) was measured using the Griess reagent system kit and the expression of cyclic adenosine monophosphate (cAMP) in the cell was measured at a wavelength of 405 nm with the ELISA reader using the cyclic AMP EIA kit. Exposure of human umbilical vein endothelial cells (HUVEC) to a high glucose concentration decreased NO and endothelial nitric oxide synthase (eNOS) levels but increased inducible NOS (iNOS) levels. However, when HUVECs were pretreated with GLP-1, a reduction of iNOS expression was observed and the expression of eNOS and NO were increased, as opposed to pretreatment with GIP. The results differed according to the response of cAMP, the second messenger of incretin hormones: The GIP pretreatment group did not exhibit an increase in cAMP levels while the GLP-1 pretreatment group did. The results of the present study provide evidence that GLP-1, but not GIP, has a protective effect on endothelial function associated with cardiovascular disease, as it is associated with increased eNOS expression and the levels of NO. This effect may be due to an increase in the cAMP concentration during hyperglycemic events.

Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypocalciuria, and hypomagnesemia. The clinical course of Gitelman syndrome in pregnant women remains unclear, but it is thought to be benign. We report here the first Korean case of atypical eclampsia in a 31-year-old who was diagnosed with Gitelman syndrome incidentally during an antenatal screening test. The patient did well during pregnancy despite significant hypokalemia. At 33 weeks' gestation, the patient exhibited eclampsia, hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and renal insufficiency without significant hypertension or proteinuria. We explain this unusual clinical course through a review of the relevant literature.

A novel Gram-stain-negative, motile by gliding, and aerobic bacterial strain, designated SA31T, was isolated from reclaimed saline land soil near a lake in Taean-gun, South Korea. Cells of the isolate formed ivory-coloured colonies. Growth occurred at 10-35 °C (optimum 25-30 °C), pH 6.0-9.0 (optimum pH 7.0-7.5), and 0-2.0 % (w/v) NaCl (optimum 0 %). Based on similarities of 16S rRNA gene sequences, strain SA31T was mostly affiliated with the genus Flavobacterium, exhibiting the highest sequence similarities with Flavobacterium palustre S44T (96.0 %), Flavobacterium glycines Gm-149T (95.9 %), Flavobacterium defluvii EMB117T (95.7 %) and Flavobacterium daejeonense GH1-10T (95.6 %). Phylogenetic analysis based on 16S rRNA gene sequences also indicated that strain SA31T was clustered with Flavobacterium daejeonense GH1-10T and Flavobacterium glycines Gm-149T. The predominant fatty acids (>7 % of total) of strain SA31T were iso-C15 : 0, summed feature 3 (C16 : 1ω7с and/or C16 : 1ω6с), iso-C17 : 0 3-OH and iso-C15 : 0 3-OH. The major polar lipids of the isolate comprised phosphatidylethanolamine, one unknown aminolipid, one unknown glycolipid, one unknown aminophospholipid and three unknown lipids. The major respiratory quinone was MK-6. The genomic DNA G+C content of strain SA31T was 33.5 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic analyses, strain SA31T represents a novel species the genus Flavobacterium, for which the name Flavobacterium eburneum sp. nov. is proposed. The type strain is SA31T (=KACC 18743T=JCM 31221T).

Bartter syndrome (BS) I-IV is a rare autosomal recessive disorder affecting salt reabsorption in the thick ascending limb of the loop of Henle. This report highlights clinicopathological findings and genetic studies of classic BS in a 22-year-old female patient who presented with persistent mild proteinuria for 2 years. A renal biopsy demonstrated a mild to moderate increase in the mesangial cells and matrix of most glomeruli, along with marked juxtaglomerular cell hyperplasia. These findings suggested BS associated with mild IgA nephropathy. Focal tubular atrophy, interstitial fibrosis, and lymphocytic infiltration were also observed. A genetic study of the patient and her parents revealed a mutation of the CLCNKB genes. The patient was diagnosed with BS, type III. This case represents an atypical presentation of classic BS in an adult patient. Pathologic findings of renal biopsy combined with genetic analysis and clinicolaboratory findings are important in making an accurate diagnosis.