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Background Intradialytic hypotension (IDH) is a serious complication of hemodialysis (HD) associated with increased risks of cardiovascular morbidity and mortality. However, its accurate prediction remains a clinical challenge. The aim of this study was to develop a deep learning–based artificial intelligence (AI) model to predict IDH using pre-dialysis features. Methods Data from 2,007 patients with 943,220 HD sessions at seven university hospitals were used. The performance of deep learning model was compared with 3 machine learning models (logistic regression, random forest, and XGBoost). Results IDH occurred in 5.39% of all studied HD sessions. A lower pre-dialysis blood pressure (BP), and a higher ultrafiltration (UF) target rate and interdialytic weight gain in IDH sessions compared to non-IDH sessions, and the occurrence of IDH in previous sessions was more frequent among IDH sessions compared to non-IDH sessions. Matthews correlation coefficient (MCC) and macro-averaged F1 score were used to evaluate both positive and negative prediction performances. Both values were similar in logistic regression, random forest, XGBoost, and deep learning models, developed with data from a single session. When combining data from the previous three sessions, the prediction performance of the deep learning model improved and became superior to that of other models. The common top-ranked features for IDH prediction were mean systolic BP (SBP) during the previous session, UF target rate, pre-dialysis SBP, and IDH experience during the previous session. Conclusions Our AI model predicts IDH accurately, suggesting it as a reliable tool for HD treatment.

Objectives To explore the possibility of kidney organoids generated using patient derived human induced pluripotent stem cells (hiPSC) for modeling of Fabry disease nephropathy (FDN). Methods First, we generated hiPSC line using peripheral blood mononuclear cells (PBMCs) from two male FD-patients with different types of GLA mutation: a classic type mutation (CMC-Fb-001) and a non-classic type (CMC-Fb-003) mutation. Second, we generated kidney organoids using wild-type (WT) hiPSC (WTC-11) and mutant hiPSCs (CMC-Fb-001 and CMC-Fb-003). We then compared alpha-galactosidase A (α-GalA) activity, deposition of globotriaosylceremide (Gb-3), and zebra body formation under electromicroscopy (EM). Results Both FD patients derived hiPSCs had the same mutations as those detected in PBMCs of patients, showing typical pluripotency markers, normal karyotyping, and successful tri-lineage differentiation. Kidney organoids generated using WT-hiPSC and both FD patients derived hiPSCs expressed typical nephron markers without structural deformity. Activity of α-GalA was decreased and deposition of Gb-3 was increased in FD patients derived hiPSCs and kidney organoids in comparison with WT, with such changes being far more significant in CMC-Fb-001 than in CMC-Fb-003. In EM finding, multi-lammelated inclusion body was detected in both CMC-Fb-001 and CMC-Fb-003 kidney organoids, but not in WT. Conclusions Kidney organoids generated using hiPSCs from male FD patients might recapitulate the disease phenotype and represent the severity of FD according to the GLA mutation type.

Renal fibrosis, the final pathway of chronic kidney disease, is caused by genetic and epigenetic mechanisms. Although DNA methylation has drawn attention as a developing mechanism of renal fibrosis, its contribution to renal fibrosis has not been clarified. To address this issue, the effect of zebularine, a DNA methyltransferase inhibitor, on renal inflammation and fibrosis in the murine unilateral ureteral obstruction (UUO) model was analyzed. Zebularine significantly attenuated renal tubulointerstitial fibrosis and inflammation. Zebularine decreased trichrome, α-smooth muscle actin, collagen IV, and transforming growth factor-β1 staining by 56.2%. 21.3%, 30.3%, and 29.9%, respectively, at 3 days, and by 54.6%, 41.9%, 45.9%, and 61.7%, respectively, at 7 days after UUO. Zebularine downregulated mRNA expression levels of matrix metalloproteinase (MMP)-2, MMP-9, fibronectin, and Snail1 by 48.6%. 71.4%, 31.8%, and 42.4%, respectively, at 7 days after UUO. Zebularine also suppressed the activation of nuclear factor-κB (NF-κB) and the expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, by 69.8%, 74.9%, and 69.6%, respectively, in obstructed kidneys. Furthermore, inhibiting DNA methyltransferase buttressed the nuclear expression of nuclear factor (erythroid-derived 2)-like factor 2, which upregulated downstream effectors such as catalase (1.838-fold increase at 7 days, p < 0.01), superoxide dismutase 1 (1.494-fold increase at 7 days, p < 0.05), and NAD(P)H: quinone oxidoreduate-1 (1.376-fold increase at 7 days, p < 0.05) in obstructed kidneys. Collectively, these findings suggest that inhibiting DNA methylation restores the disrupted balance between pro-inflammatory and anti-inflammatory pathways to alleviate renal inflammation and fibrosis. Therefore, these results highlight the possibility of DNA methyltransferases as therapeutic targets for treating renal inflammation and fibrosis.

Background: Fabry disease is a rare X-linked genetic lysosomal disorder caused by mutations in the GLA gene encoding alpha-galac tosidase A. Despite some data showing that profibrotic and proinflammatory cytokines and oxidative stress could be involved in Fabry disease-related renal injury, the pathogenic link between metabolic derangement within cells and renal injury remains unclear. Methods: Renal fibrosis was triggered by unilateral ureteral obstruction (UUO) in mice with Fabry disease to investigate the pathogen ic mechanism leading to fibrosis in diseased kidneys. Results: Compared to kidneys of wild-type mice, lamellar inclusion bodies were recognized in proximal tubules of mice with Fabry dis ease. Sirius red and trichrome staining revealed significantly increased fibrosis in all UUO kidneys, though it was more prominent in obstructed Fabry kidneys. Renal messenger RNA levels of inflammatory cytokines and profibrotic factors were increased in all UUO kidneys compared to sham-operated kidneys but were not significantly different between UUO control and UUO Fabry mice. Protein levels of Nox2, Nox4, NQO1, catalase, SOD1, SOD2, and Nrf2 were not significantly different between UUO control and UUO Fabry kidneys, while the protein contents of LC3-II and LC3-I and expression of Beclin1 were significantly decreased in UUO kidneys of Fabry disease mouse models compared with wild-type mice. Notably, TUNEL-positive cells were elevated in obstructed kidneys of Fabry dis ease mice compared to wild-type control and UUO mice. Conclusion: These findings suggest that impaired autophagy and enhanced apoptosis are probable mechanisms involved in en hanced renal fibrosis under the stimulus of UUO in Fabry disease.

Background/Aims: Because weight control is important in treatment of type 2 diabetes, it is essential to understand the associations between weight change and the risk of microvascular complications among patients with type 2 diabetes. We examined whether weight changes early after new-onset diabetes have an impact on the clinical outcomes of diabetic nephropathy and retinopathy. Methods: Using the Korean National Health Insurance Service-National Health Screening Cohort database, 181,872 patients newly diagnosed with type 2 dia betes who were free of end-stage renal disease (ESRD) and proliferative diabetic retinopathy (PDR) during 2007 to 2012 were followed to the end of 2016. Weight change was defined as the difference in body weight from the time of diabetes di agnosis to 2 years later. Results: We identified 180 cases of ESRD and 780 cases of PDR followed up for a median of 5.5 years from the index year at 2 years after diagnosis. Those with 5% to 10% weight gain showed a significantly higher hazard ratio (HR) for ESRD, compared with those with ≤ 5% weight change after adjusting for several con founding factors, including the baseline estimated glomerular filtration rate (HR, 1.75; 95% confidence interval [CI], 1.14 to 2.70). Those with ≥ 10% weight loss showed the lowest HR for PDR (HR, 0.52; 95% CI, 0.33 to 0.83), whereas those with ≥ 10% weight gain showed the highest HR for PDR (HR, 3.20; 95% CI, 2.51 to 4.08). Conclusions: Weight gain after new-onset diabetes was associated with increased risk of ESRD and PDR whereas weight loss with decreased risk of PDR, but not ESRD.

Aims Status of metabolic syndrome (MetS) and its components can changes over time. However, few studies have investigated the cumulative burden of MetS and its components on clinical renal outcomes in the general population. Methods Using nationally representative data from the Korean National Health Insurance System, 2,664,270 subjects who underwent health examinations for four consecutive years and were free from end-stage renal disease (ESRD) from 2009 to 2013. We used exposure-weighted scores in two ways: (1) cumulative number of MetS diagnosis at each health examination (MetS exposure score, range: 0 to 4); (2) the composite of its five components (MetS component exposure score, 0 to a maximum of 20). Hazard ratio and 95% confidence interval (CI) values for ESRD were analysed using the Cox proportional-hazard model. Results Overall, 63.4%, 14. 0%, 8.2%, 6.2% and 8. 0% met the MetS diagnostic criteria 0 to 4, respectively. After a median follow up of 5.3 years, 2,303 incident ESRD cases were identified. In the multivariate adjusted model, the hazard ratio (HR) and 95% confidence interval (CI) for the development of ESRD showed a gradual increase with increasing exposure score of MetS and its components, which was independent of age, sex, and baseline estimated glomerular filtration rate (each p for trend < 0. 0001). The HR of ESRD was 6.48 (95% CI, 4.12 to 10.20) in subjects with a MetS component exposure score of 20 compared with those with a score of 0. Conclusions This provides evidence supporting the strategy of reducing MetS exposure to prevent the development of ESRD in the general population. Presentation: No date and time listed

We explored the utility of Kinect sensor-based upper extremity reachable workspace measure in healthy adults aged over 65 years.Forty-three healthy older subjects (19 men and 24 women) aged over 65 years and 22 healthy young subjects (11 men and 11 women) were included. All participants were ambulatory and perform the activities of daily living independently. Three-dimensional reachable workspace data were acquired for both arms using the Kinect sensor. We evaluated hand grip strength, manual muscle shoulder strength, and the active shoulder ranges of motion of the dominant and non-dominant sides. We assessed upper limb function using the Disabilities of Arm, Shoulder, and Hand (DASH) instrument and the health-related quality of life employing the descriptive EQ-5D-5L system.The quadrant 3 relative surface area in older adults was significantly smaller than that of young adults (both dominant and non-dominant sides), while the total and quadrants 1, 2, and 4 relative surface areas did not differ between older and young adults. However, the quadrant 3 relative surface area did not correlate with the DASH or EQ5D scores. The total and quadrant 1, 2, and 4 relative surface areas of the dominant side significantly correlated with the DASH score. The quadrant 4 relative surface area of the dominant side significantly correlated with the EQ5D score.Kinect sensor-based, three-dimensional, reachable workspace analysis may be useful to evaluate upper limb function in older adults.

Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulonephritis characterized by diffuse deposits of IgM in the glomerular mesangium. However, its renal prognosis remains unknown. We compared renal outcomes of IgMN patients with those of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or mesangial proliferative glomerulonephritis (MsPGN) from a prospective observational cohort, with 1791 patients undergoing native kidney biopsy in eight hospitals affiliated with The Catholic University of Korea between December 2014 and October 2020. IgMN had more mesangial proliferation and matrix expansion than MsPGN and more tubular atrophy and interstitial fibrosis than MCD. IgMN patients had decreased eGFR than MCD patients in the earlier follow-up. However, there was no significant difference in urine protein or eGFR among all patients at the last follow-up. When IgMN was divided into three subtypes, patients with FSGS-like IgMN tended to have lower eGFR than those with MCD-like or MsPGN-like IgMN but higher proteinuria than MsPGN-like IgMN without showing a significant difference. The presence of hypertension at the time of kidney biopsy predicted ≥20% decline of eGFR over two years in IgMN patients. Our data indicate that IgMN would have a clinical course and renal prognosis similar to MCD, FSGS, and MsPGN.

Objective Obesity and type 2 diabetes are becoming increasingly prevalent worldwide and are both associated with the increased incidence of kidney and bladder cancers. However, previous reports have provided conflicting results. We investigated the impact of body mass index (BMI) and diabetes on the incidence of both cancers in the general population. Methods Using nationally representative data from the Korean National Health Insurance System, 9,777,133 subjects without any malignancy who underwent health examinations in 2009 were followed to the end of 2017. Results After a median follow-up period of 8.32 years, 12,544 incidents of kidney cancer and 15,137 incidents of bladder cancer were identified. The hazard ratio (HR) for kidney cancer was the lowest in people with a BMI 2 (HR: 0.82, 95% confidence interval (CI): 0.72–0.94) and the highest in those with a BMI ≥30 kg/m2 (HR: 1.71, 95% CI: 1.57–1.87) compared to a reference BMI group (18.5–23 kg/m2). In subjects with diabetes, obesity was associated with increased risk of kidney cancer, although the HRs were lower than observed in those without diabetes. Otherwise, there was a reduction in risk of bladder cancer with obesity in men and the HR for bladder cancer was not affected by BMI increase in women. There was a strongly positive association between diabetes and bladder cancer in the total study population. Conclusions Obesity was a strong risk factors for kidney cancer, whereas the association between obesity and bladder cancer differed by gender. The subjects with diabetes had a higher risk for both cancers than those without diabetes.

Background and aims There is a growing evidence demonstrating an association between dyslipidemia and progression of chronic kidney disease (CKD), but results on the effects of high-density lipoprotein cholesterol (HDL-C) on renal outcome have been conflicting. In this study, the relationship between HDL-C variability and the risk for progression to end-stage renal disease (ESRD) was investigated. Methods This study analyzed data of 4,283,318 subjects who were free of ESRD at the time of enrollment, received more than three medical examinations from 2009 to 2012, and were followed to the end of 2015, based on the Korean National Health Insurance Service database. HDL-C variability was measured using the standard deviation, coefficient of variation, average real variability and variability independent of the mean (VIM). Results A total of 2,095 new cases of ESRD were observed during a median follow up of 3.38 years. There was a graded association between higher HDL-C variability and incident ESRD. In the multivariable adjusted model, hazard ratio comparing the highest and lowest quartiles of VIM of HDL-C was 1.82 (95% confidence interval, 1.58–2.09). The results were consistent when the variability of HDL-C was modeled using standard deviation, coefficient of variation and average real variability and were independent of other confounding factors, including the presence of CKD. Conclusions HDL-C variability independently predicted an increased risk for developing ESRD. Our findings suggest that identification of HDL-C variability may help improve risk stratification for the prevention of ESRD.

The objective of this study was to investigate the optimal blood pressure (BP) target to prevent development of cardiovascular diseases (CVDs) in Korean subjects with type 2 diabetes mellitus. Using the Korean National Health Insurance Service database, 2 262 725 subjects with type 2 diabetes mellitus who underwent regular health checks between 2009 and 2012 were included. Subjects with previous CVDs were excluded. Participants were grouped by 10-mm Hg intervals of observed systolic BP (SBP) by 5-mm Hg intervals of diastolic BP. There were 124 466 deaths (5.50%), 67 235 cases of stroke (2.97%), and 41 726 myocardial infarctions (1.84%) during a median follow-up of 6.5 years. Compared with SBP 110 to 119 mm Hg, there was no increased risk among subjects with SBP 120 to 129 mm Hg, but SBP ≥130 mm Hg was associated with a significant increase in the incidence of CVDs. SBP 130 to 139 mm Hg was associated with a significant increase in the incidence of stroke (hazard ratio, 1.15; 95% CI, 1.12–1.18) and myocardial infarctions (hazard ratio, 1.05; 95% CI, 1.02–1.09) compared with SBP 110 to 119 mm Hg. Subjects with diastolic BP 80 to 84 mm Hg had a higher risk of CVDs than subjects with diastolic BP 75 to 79 mm Hg. The overall relationship between BP and CVD risk was positive, with a greater strength observed for younger age groups. The optimal cutoff for Korean patients with type 2 diabetes mellitus associated with lower CVD risk may be 130 mm Hg for SBP or 80 mm Hg for diastolic BP.

Aims To investigate the effectiveness of sodium-glucose co-transporter-2 (SGLT2) inhibitors on the risk of progression to end-stage renal disease (ESRD) and all-cause mortality in a broad range of patients with type 2 diabetes (T2D) using a Korean nationwide cohort.Materials and Methods Using data from the Korean National Health Insurance Service database from January 2014 to December 2017, a total of 701 674 patients were identified with T2D. We divided these patients into new users of SGLT2 inhibitors and new users of other glucose-lowering drugs (oGLDs). Using propensity scores, patients in the two groups were matched 1:1. We assessed the risk of ESRD and all-cause death.Results There were 45 016 patients in each group, and baseline characteristics were well balanced between the groups. The patients' mean age was 58.1 +/- 10.6 years and mean estimated glomerular filtration rate (eGFR) was 89.2 +/- 27.4 mL/min/1.73m(2), and 8% of patients had proteinuria. We identified 167 incident ESRD cases and 1070 all-cause deaths during follow-up. Use of SGLT2 inhibitors versus oGLDs was associated with a lower risk of ESRD (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.34 to 0.65) and all-cause death (HR 0.82, 95% CI 0.73 to 0.93). In a subgroup analysis by eGFR, initiation of SGLT2 inhibitor treatment, compared with oGLD treatment, was associated with lower risk of progression to ESRD among patients with eGFR 60 to 90 mL/min/1.73m(2) and those with eGFR = 90 and 60 to 90 mL/min/1.73m(2).Conclusion In this large nationwide study of Korean patients with T2D, initiation of SGLT2 inhibitors versus oGLDs was associated with lower risk of ESRD and all-cause death.

Background and Aims Few studies have investigated the impact of a change in metabolic syndrome (MetS) components on clinical renal outcomes in the general population. Method Using nationally representative data from the Korean National Health Insurance System, 13,310,924 subjects who underwent two health examinations over 2 years and were free from end-stage renal disease (ESRD) from 2009 to 2012 were followed to the end of 2016. The subjects were divided into four groups according to the change in MetS components between the two visits over 2 years: no MetS (–/–), post-MetS (–/+), pre-MetS (+/–), and both MetS (+/+). Results After a median follow up of 5.11 years, 18,582 incident ESRD cases were identified. In the multivariate adjusted model, the hazard ratio (HR) and 95% confidence interval (CI) for the development of ESRD in the both-MetS (+/+) group compared with the no-MetS (–/–) group was 5.65 (95% CI, 5.42–5.89), which was independent of age, sex, and baseline estimated glomerular filtration rate. Additionally, the HR for the pre-MetS (+/-) group versus the no-MetS (–/–) group was 2.28 (2.15–2.42). In subgroup analysis according to renal function, the impact of a change in MetS on the incidence of ESRD was more pronounced in individuals with advanced renal dysfunction. Subjects with resolved MetS components had a decreased risk of ESRD, but not as low as those that never had MetS components. Conclusion This provides evidence supporting the strategy of modulating MetS in the general population to prevent the development of ESRD.

We investigated the relationship of changes in Metabolic syndrome (MetS) and its components with the risk of type 2 diabetes (T2D) in South Korea. Records of 10,806,716 adults aged ≥ 20 years without a history of T2D between 2009 and 2015 were retrieved from database of the South Korean National Health Insurance Service and analyzed. Changes in metabolic components were monitored over a two-year period with follow-up occurring at an average of 4.087 years. During the follow-up period, 848,859 individuals were diagnosed with T2D. The risk of diabetes was lowered with a decrease in the number of MetS components at baseline and the second visit (p for trend

IgA nephropathy (IgAN) is a globally well-known primary glomerular nephropathy. Hypertriglyceridemia (HTG) is one factor contributing to atherosclerosis and is a common complication of renal failure. HTG is a significant risk factor for decreased renal function in patients with IgAN. We evaluated the association of HTG with the histopathological features of IgAN patients. A total of 480 patients diagnosed with IgAN via kidney biopsy from eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea were included in the final cohort. Pathological features were evaluated by eight expert pathologists with hospital consensus. HTG was defined as a serum triglyceride (TG) level of ≥150 mg/dL. In the study population analysis, the HTG group was older, with more males, higher body mass index (BMI), low-density lipoprotein cholesterol (LDL-C) and spot urine protein ratio, and lower estimated glomerular filtration rate (eGFR). In the lipid profile analysis, eGFR was negatively correlated with TGs/ high-density lipoprotein cholesterol (HDL) and triglyceride-glucose index (TyG). Proteinuria positively correlated with TGs/HDL, non-HDL/HDL, LDL/HDL, TyG, TGs and LDL. The percentages of global sclerosis (GS), segmental sclerosis (SS) and capsular adhesion (CA), and the scores for mesangial matrix expansion (MME) and mesangial cell proliferation (MCP), were more elevated in the HTG group compared to the normal TG group. Multivariable linear regression analysis showed that the percentages of global sclerosis, segmental sclerosis and capsular adhesion, as well as the scores for mesangial matrix expansion and mesangial cell proliferation, were positively associated with TG level. In binary logistic regression, the HTG group showed a higher risk for global sclerosis and segmental sclerosis. In conclusion, HTG is a significant risk factor for glomerulosclerosis in IgAN.

Objective— Recent data suggest that visit-to-visit variability of cholesterol is associated with cardiovascular events. We evaluated the role of lipid variability as a determinant of end-stage renal disease (ESRD). Approach and Results— Using nationally representative data from the Korean National Health Insurance System, 8 493 277 subjects who were free of ESRD and who underwent ≥3 health examinations during 2005 to 2010 were followed to the end of 2015. Total cholesterol (TC) variability was measured using the coefficient of variation, SD, and the variability independent of the mean. The primary outcome was the development of ESRD, defined as a combination of the relevant disease code and the initiation of renal replacement therapy. There were 11 247 cases of ESRD during a median follow-up of 6.1 years. There was a graded association between a higher TC variability and incident ESRD. In the multivariable adjusted model, the hazard ratios and 95% confidence intervals comparing the highest versus lowest quartiles of coefficient of variation of TC were 2.66 (95% confidence interval, 2.52–2.82). The results were consistent when the variability of TC was modeled using SD and variability independent of the mean and were independent of preexisting chronic kidney disease. Conclusions— Increasing TC variability was associated with an increasing incidence of ESRD.

Introduction In this study we evaluated the effect of electromyostimulation (EMS) on myosin heavy chain (MHC) isoform expression in denervated rat muscles to determine the optimal timing for EMS application. Methods EMS was initiated on post-injury day 1 for the group with denervation receiving immediate EMS (DIEMS) and on post-injury day 15 for the group with denervation receiving delayed EMS (DDEMS) in rat denervated muscles. Muscle wet weight and muscle fiber cross-sectional area (FCSA) were measured. MHC isoforms were analyzed in both protein homogenates and single muscle fibers. Results The expression levels of IIx and IIb isoforms of MHC were significantly lower and higher, respectively, in the gastrocnemius muscles of the DIEMS group, but not the DDEMS group. The DIEMS group also showed larger FCSA and a lower proportion of hybrid single fibers compared with the DDEMS group. Discussion These results indicate that immediate EMS is more effective than delayed EMS for aiding recovery of denervation-induced MHC changes. Muscle Nerve 56: E154-E161, 2017.

p300/CBP-associated factor (PCAF), a histone acetyltransferase, is involved in many cellular processes such as differentiation, proliferation, apoptosis, and reaction to cell damage by modulating the activities of several genes and proteins through the acetylation of either the histones or transcription factors. Here, we examined a pathogenic role of PCAF and its potential as a novel therapeutic target in the progression of renal tubulointerstitial fibrosis induced by non-diabetic unilateral ureteral obstruction (UUO) in male C57BL/6 mice. Administration of garcinol, a PCAF inhibitor, reversed a UUO-induced increase in the renal expression of total PCAF and histone 3 lysine 9 acetylation and reduced positive areas of trichrome and &alpha, smooth muscle actin and collagen content. Treatment with garcinol also decreased mRNA levels of transforming growth factor-&beta, matrix metalloproteinase (MMP)-2, MMP-9, and fibronectin. Furthermore, garcinol suppressed nuclear factor-&kappa, B (NF-&kappa, B) and pro-inflammatory cytokines such as tumor necrosis factor-&alpha, and IL-6, whereas it preserved the nuclear expression of nuclear factor erythroid-derived 2-like factor 2 (Nrf2) and levels of Nrf2-dependent antioxidants including heme oxygense-1, catalase, superoxide dismutase 1, and NAD(P)H:quinone oxidoreductase 1. These results suggest that the inhibition of inordinately enhanced PCAF could mitigate renal fibrosis by redressing aberrant balance between inflammatory signaling and antioxidant response through the modulation of NF-&kappa, B and Nrf2.

Aims The status of metabolic abnormalities including impaired fasting glucose (IFG) can change over time, yet little is known about how exposure duration to IFG is related to diabetes risk. Methods Using nationally representative data from the Korean National Health Insurance system, 2,513,127 people who were free of diabetes and who received four consecutive annual health examinations commencing in 2006 or 2007 were followed up at the end of 2016. IFG was defined as fasting blood glucose levels of 100–125 mg/dL. Participants were classified numerically according to the cumulative number of IFG diagnoses. Results Over 4 years, 53% of the population participants remained normoglycemic, while 3% had persistent IFG and 44% had intermittent IFG. The risk of type 2 diabetes mellitus (DM) increased gradually with increasing IFG exposure score. Subjects with an IFG exposure score of 2, 3, or 4 had a 3.75- to 9.77-fold increased hazard ratio (HR) for incident diabetes (IFG exposure score 0 reference; score 2, HR 3.75, 95% confidence interval [CI] 3.67–3.83; score 3, HR 6.21, 95% CI 6.08–6.36; score 4, HR 9.77, 95% CI 9.53–10.02). Conclusions Cumulative IFG exposure was associated with a higher risk of type 2 DM in a dose–response fashion.

Hyperuricemia is a significant risk factor for cardiovascular morbidity and chronic kidney disease progression. IgA nephropathy (IgAN) is a well-known primary glomerular nephropathy. Hyperuricemia is associated with a poor prognosis in IgAN patients. We evaluated the association of hyperuricemia with the histopathological severity of IgAN in male and female patients, 658 patients diagnosed with IgAN via kidney biopsy were initially included. Baseline patient data were collected by eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea. Pathological features were independently evaluated by eight expert pathologists working in the hospitals, and the consensus was reached. Of the initial 658 patients, 517 were finally included (253 males and 264 females). Hyperuricemia was defined as a serum uric acid (UA) level &gt, 7.0 mg/dL for males and &gt, 5.6 mg/dL for females, 108 (42.7%) males and 95 (35.9%) females exhibited hyperuricemia. Compared to the patients with normal UA levels, the global glomerulosclerosis, segmental sclerosis, mesangial matrix expansion (MME), endocapillary proliferation (ECP), interstitial fibrosis (IF), and tubular atrophy (TA) scores were higher in hyperuricemic males and females. In multivariable linear regression, the serum UA level correlated significantly with the MME, ECP, IF, and TA scores of female IgAN patients only.

Several studies reported the effect of obesity on the progression of IgA nephropathy (IgAN). However, the impact of obesity on the clinicopathologic presentation of IgAN remains uncertain. This is a retrospective cross-sectional study from eight university hospitals in South Korea. Patients were categorized into three groups using the Asia-Pacific obesity classification based on body mass index (BMI). Clinical and histopathologic data at the time of renal biopsy were analyzed. Among 537 patients with IgAN, the obese group was more hypertensive and had lower estimated glomerular filtration rate and more proteinuria than other groups. The histologic scores for mesangial matrix expansion (MME), interstitial fibrosis, tubular atrophy, and mesangial C3 deposition differed significantly between the three groups. Among these histopathologic parameters, BMI was independently positively associated with MME score on multivariable linear regression analysis (p = 0.028). Using multivariable logistic regression analysis, the obese group was independently associated with higher MME scores compared to the normal weight/overweight group (p = 0.020). However, BMI was not independently associated with estimated glomerular filtration rate or proteinuria on multivariable analysis. Obesity was independently associated with severe MME in patients with IgAN. Obesity may play an important pathogenetic role in mesangial lesions seen in IgAN.

Objective It remains unclear which specific combinations of metabolic syndrome (MetS) components confer a higher risk of type 2 diabetes mellitus (T2DM). This study examined the relation of each and combinations of MetS components with the risk of T2DM. Methods We studied the records of 19,475,643 adults aged ≥ 20 years with no history of T2DM from the database of the Korean National Health Insurance Service covering 2009 to 2012. The hazard ratios (HRs) and confidence intervals (CIs) of T2DM were estimated using Cox proportional hazards models. Results During a median follow-up of 5.13 years, 1,906,963 individuals were diagnosed with T2DM. The multivariable-adjusted HRs for T2DM were 1.86 for MetS, 1.821 for elevated fasting plasma glucose (FPG), 1.484 for elevated triglycerides, 1.415 for reduced high-density lipoprotein (HDL) cholesterol, 1.413 for elevated blood pressure (BP), and 1.17 for abdominal obesity compared with those without. In the combinations of two components excluding elevated FPG, subjects with elevated triglycerides and reduced HDL cholesterol had the highest risk of T2DM (HR 1.71; 95% CI, 1.695–1.725). In three components, the highest risk combination was elevated FPG, elevated triglycerides, and reduced HDL cholesterol (HR 3.342; 95% CI, 3.308–3.376). Conclusions The combination of elevated triglycerides and reduced HDL cholesterol were more strongly associated with an increased risk of T2DM than other combinations except for elevated FPG.

Background Because weight control is a cornerstone of diabetes management, it is important to understand the relationship of weight change to risk of cardiovascular disease (CVD) among patients with type 2 diabetes mellitus (DM). We aimed to investigate whether changes in weight early after diagnosis influence the incidence of CVD and all-cause mortality in patients with type 2 DM. Methods Using nationally representative data from the Korean National Health Insurance System, 173,246 subjects with new-onset DM who underwent health examinations during 2007–2012 were included. Weight was measured at the time of diabetes diagnosis and 2 years later. Weight change over 2 years was divided into five categories of 5% weight change, from weight loss ≥ − 10% to weight gain ≥ 10%. Results There were 3113 deaths (1.8%), 2060 cases of stroke (1.2%), and 1767 myocardial infarctions (MIs) (1.0%) during a median follow-up of 5.5 years. Subjects with weight gain ≥ 10% had a significantly higher risk of stroke (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.23–1.84), compared with the group with stable weight. There was no significant association between weight change after diagnosis of DM and incident MI. All-cause mortality showed a U-shaped curve according to weight change. The group with weight loss ≥ − 10% had the highest HR for all-cause mortality (HR 1.86; 95% CI 1.61–2.14) and the HR for weight gain ≥ 10% was 1.61 (95% CI 1.37–1.89). Conclusions Weight changes of more than 10% after diabetes diagnosis were associated with higher mortality and over 10% weight gain was associated with increased risk of stroke. Electronic supplementary material The online version of this article (10.1186/s12933-019-0838-9) contains supplementary material, which is available to authorized users.

OBJECTIVE This study examined the association between baseline BMI, percentage weight change, and the risk of dementia in patients newly diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS Using the South Korean National Health Insurance Service-National Health Screening Cohort database, we identified 167,876 subjects aged ≥40 years diagnosed with new-onset type 2 diabetes between 2007 and 2012. Their weight changes were monitored for ∼2 years after diagnosis, with follow-up assessments occurring for an average of 3.5 years. The hazard ratios (HRs) and Bonferroni-adjusted 95% CIs of all-cause dementia, Alzheimer disease (AD), and vascular dementia were estimated using multivariable Cox proportional hazards regression models. RESULTS We identified 2,563 incident dementia cases during follow-up. Baseline BMI among patients with new-onset type 2 diabetes was inversely associated with the risk of all-cause dementia and AD, independent of confounding variables (P for trend 10% (1.34 [95% CI 1.11–1.63] and 1.38 [1.08–1.76], respectively). Additionally, weight loss >10% was associated with an increased risk of AD (HR 1.26 [95% CI 1.01–1.59]). CONCLUSIONS A lower baseline BMI was associated with increased risks of all-cause dementia and AD in patients with new-onset type 2 diabetes. Weight loss or weight gain after the diagnosis of diabetes was associated with an increased risk of all-cause dementia. Weight loss was associated with an increased risk of AD.

Although the mechanism of cyclosporine A (CsA)-induced renal injury remains to be fully elucidated, accumulating evidence suggests that oxidative stress is critical in producing CsA-induced structural and functional renal impairment. The present study investigated the effect of D-pinitol, a cyclitol present in soybean, on chronic CsA nephropathy. Male ICR mice were treated with vehicle, CsA (30 mg/kg/day), D-pinitol (50 mg/kg/day) or a combination of CsA and D-pinitol for 28 days. To assess which pathway responding to oxidative stress is augmented by D-pinitol, the expression levels of several antioxidant enzymes and their possible regulators were measured. Treatment with D-pinitol significantly suppressed the increase of serum creatinine and decrease of urine osmolality, compared with the CsA control group. Histological examination of Masson's trichrome- and α-smooth muscle actin-stained renal tissue demonstrated that the CsA-induced tubulointerstitial fibrosis and inflammation were attenuated by D-pinitol. Following the administration of D-pinitol, there were increased expression levels of heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1, superoxide dismutase 1 and catalase in CsA-treated kidneys. In addition, D-pinitol increased the level of sirtuin 1 (Sirt1), and the total and nuclear expression levels of nuclear erythroid factor 2-related factor 2 (Nrf2), suggesting that activation of the Sirt1 and Nrf2 pathways may induce the cellular antioxi dant system against CsA-induced nephropathy. Collectively, these data suggested that D-pinitol may protect the kidney from CsA-induced fibrosis, and that this renoprotective effect of D-pinitol was due to the inhibition of oxidative stress through the activation of Sirt1 and Nrf2, and the subsequent enhancement of antioxidant enzymes.

Background/Aims: β2-Microglobulin (β2-M) is a surrogate marker of middle-molecule uremic toxins and is associated with mortality in chronic hemodialysis patients. However, the impact of serum β2-M levels on mortality in peritoneal dialysis (PD) patients is uncertain. The purpose of this study was to examine the association of serum β2-M levels with all-cause mortality in PD patients. Methods: A total of 771 PD patients were selected from the Clinical Research Center registry for end-stage renal disease cohort in Korea. Patients were categorized into 3 groups by tertiles of serum β2-M levels. The primary outcome was all-cause mortality. Results: The median value of serum β2-M was 23.6 mg/l (interquartile range 14.8-33.4 mg/l), and the median follow-up period was 39 months. The Kaplan-Meier analysis showed that the all-cause mortality rate was significantly different according to tertiles of serum β2-M in PD patients (p = 0.03, log-rank). Multivariate Cox proportional analysis showed that the hazards ratio for all-cause mortality was 1.02 (95% CI 1.01-1.04, p = 0.006) per 1 mg/l increase in β2-M after adjustment for multiple confounding factors that relate to malnutrition and inflammation marker. However, serum β2-M was not associated with all-cause mortality after adjustment for residual renal clearance. Conclusions: These results are supportive of the potential role of the serum β2-M level as a predictor of mortality in PD patients.

Background: Impaired vitamin D metabolism may contribute to the development and progression of chronic kidney disease. The purpose of this study was to determine associations of circulating vitamin D with the degree of proteinuria and estimated glomerular filtration rate (eGFR) in patients with biopsy-proven glomerular diseases. Methods: Clinical and biochemical data including blood samples for 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were collected from patients at the time of kidney biopsy. Results: Serum 25(OH)D levels were not different according to eGFR. However, renal function was significantly decreased with lower serum 1,25(OH)2D levels (P < 0.001). The proportions of nephrotic-range proteinuria and renal dysfunction (eGFR ≤ 60 mL/min/1.73 m2) progressively increased with declining 1,25(OH)2D but not 25(OH)D. Multivariable linear regression analysis showed that 25(OH)D was significantly correlated with serum albumin and total cholesterol (β = 0.224, P = 0.006; β = -0.263, P = 0.001) and 1,25(OH)2D was significantly correlated with eGFR, serum albumin and phosphorus (β = 0.202, P = 0.005; β = 0.304, P < 0.001; β = -0.161, P = 0.024). In adjusted multivariable linear regression, eGFR and 24hr proteinuria were independently correlated only with 1,25(OH)2D (β = 0.154, P = 0.018; β = -0.171, P = 0.012), but not 25(OH)D. The lower level of 1,25(OH)2D was associated with the frequent use of immunosuppressive agents (P < 0.001). Conclusion: It is noteworthy in these results that circulating 1,25(OH)2D may be superior to 25(OH)D as a marker of severity of glomerular diseases.

To investigate age and gender patterns in associations between lifestyle factors and physical performance in community-dwelling older Korean adults.A cross-sectional study was conducted in a population-based sample of an urban area. Randomly sampled older Korean adults (n=664; mean age, 74.6 years) participated. Data on current physical activity level and doing exercise, social participation and hobbies, smoking status, drinking status, sleep quality, and physical performance were obtained. Binary logistic regression analyses were used to identify the age and gender patterns in associations between various lifestyle factors and physical performance.In younger (age85 years) men, significant predictors of poor physical performance by logistic regression analysis after adjusting for covariates were current physical activity time, doing exercise, and engagement in social activities. In younger women, current physical activity time and sleep quality were related to poor physical performance. In older (age ≥ 85 years) men, family gatherings were a significant factor. In older women, no lifestyle factor assessed showed a significant relationship with poor physical performance.Interventions implemented to modify lifestyle factors need to focus on age and gender subgroups in the elderly population. Lifestyle modification should be emphasised as a targeted treatment program for Korean adults aged85 years.