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Iron replacement therapy is necessary for anemia treatment in patients with advanced chronic kidney disease. Intravenous (IV) iron therapy is an efficient method for iron replacement. However, there are concerns regarding its considerable side effects, including increased risks of infection or major adverse cardiovascular events (MACE). This is a longitudinal study from a multicenter prospective cohort study conducted in the Korean end-stage renal disease population. All-cause mortality, death due to infection or MACE, hospitalization due to infection or MACE, and all adverse event of death or hospitalization due to infection or MACE were compared according to the iron replacement methods during the first 3 months of enrollment. Among 1,680 hemodialysis patients, 29.3% of patients received IV iron therapy, and 38% of patients received oral iron therapy. During the median 632 days follow-up, all-cause mortality, mortality or hospitalization due to infection or MACE, and all adverse events did not differ among iron replacement groups. There were significant differences related to the risk of all adverse events among iron replacement therapies in the log-rank test and univariate Cox regression analysis only in the prevalent dialysis patients; however, the significance was lost in multivariate Cox regression analysis. Similar results were observed in the 1-year short-term outcome analysis. High-dose IV iron did not increase adverse outcomes. All-cause mortality or all adverse events due to infection or MACE were not higher with the current clinical regimen of IV iron replacement therapy than with oral or no iron therapy in Korean hemodialysis patients.

Muscle loss is a serious complication in patients with diabetes mellitus (DM) and chronic kidney disease (CKD). However, studies on a long-term change in muscle mass presence or absence of DM and CKD are scarce. We included 6247 middle-aged adults from the Korean Genome and Epidemiology Study (KoGES) between 2001 and 2016. Bioimpedance analysis (BIA) was performed biennially. Patients were classified into four groups according to the presence or absence of DM and CKD. The primary outcome was muscle depletion, which was defined as a decline in fat-free mass index (FFMI) below the 10th percentile of all subjects. The secondary outcomes included the occurrence of cachexia, all-cause mortality, and the slopes of changes in fat-free mass and weight. During 73,059 person-years of follow-up, muscle depletion and cachexia occurred in 460 (7.4%) and 210 (3.4%), respectively. In the multivariable cause-specific hazards model, the risk of muscle depletion was significantly higher in subjects with DM alone than in those without DM and CKD (HR, 1.37; 95% CI, 1.04-1.80) and was strongly pronounced in subjects with both conditions (HR, 3.38; 95% CI, 1.30-8.75). The secondary outcome analysis showed consistent results. The annual decline rates in FFMI, fat mass, and body mass index (BMI) were the steepest in subjects with DM and CKD among the four groups. DM and CKD are synergically associated with muscle loss over time. In addition, the mortality risk is higher in individuals with muscle loss.

Ischemia-reperfusion injury is a major cause of acute kidney injury. Recent studies on the pathophysiology of ischemia-reperfusion-induced acute kidney injury showed that immunologic responses significantly affect kidney ischemia-reperfusion injury and repair. Nuclear factor (NF)-ĸB signaling, which controls cytokine production and cell survival, is significantly involved in ischemia-reperfusion-induced acute kidney injury, and its inhibition can ameliorate ischemic acute kidney injury. Using EXPLOR, a novel, optogenetically engineered exosome technology, we successfully delivered the exosomal super-repressor inhibitor of NF-ĸB (Exo-srIĸB) into B6 wild type mice before/after kidney ischemia-reperfusion surgery, and compared outcomes with those of a control exosome (Exo-Naïve)-injected group. Exo-srIĸB treatment resulted in lower levels of serum blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin in post-ischemic mice than in the Exo-Naïve treatment group. Systemic delivery of Exo-srIĸB decreased NF-ĸB activity in post-ischemic kidneys and reduced apoptosis. Post-ischemic kidneys showed decreased gene expression of pro-inflammatory cytokines and adhesion molecules with Exo-srIĸB treatment as compared with the control. Intravital imaging confirmed the uptake of exosomes in neutrophils and macrophages. Exo-srIĸB treatment also significantly affected post-ischemic kidney immune cell populations, lowering neutrophil, monocyte/macrophage, and T cell frequencies than those in the control. Thus, modulation of NF-ĸB signaling through exosomal delivery can be used as a novel therapeutic method for ischemia-reperfusion-induced acute kidney injury.

Background Although it is well known that low bone mineral density (BMD) is associated with an increased risk of cardiovascular disease (CVD) and mortality in the general population, the prognostic role of bone mineral density (BMD) has not been established in the chronic kidney disease (CKD) population. Therefore we aimed to evaluate the association between BMD and the risk of CVD and cardiovascular mortality in patients with predialysis CKD. Methods This prospective cohort study was conducted with 1957 patients with predialysis CKD Stages 1–5. BMD was measured using dual-energy X-ray absorptiometry and coronary arterial calcification (CAC) scores were evaluated using coronary computed tomography. The primary outcome was a major adverse cardiovascular event (MACE). Results When patients were classified based on total hip BMD T-score tertiles stratified by sex, the lowest BMD tertile was significantly associated with an increased risk of MACE {hazard ratio 2.16 [95% confidence interval (CI) 1.25–3.74]; P = 0.006}. This association was also shown with BMD at the femur neck but not with BMD at lumbar spine. In the subgroup of 977 patients with follow-up CACs at their fourth year, 97 (9.9%) showed accelerated CAC progression (>50/year), and BMD was inversely associated with accelerated CAC progression even after adjusting for the baseline CAC score [odds ratio 0.75 (95% CI 0.58–0.99); P = 0.039]. In addition, baseline CAC was associated with an increased risk of MACEs after adjusting for total hip T-score. Conclusions Low BMD was significantly associated with CAC progression and MACEs in patients with predialysis CKD., GRAPHICAL ABSTRACT Graphical Abstract

Longitudinal studies of the association between sex and adverse clinical outcomes in patients with chronic kidney disease (CKD) are scarce. We assessed whether major outcomes may differ by sex among CKD patients. We analyzed a total of 1780 participants with non-dialysis CKD G1-5 from the KoreaN cohort study for Outcome in patients with Chronic Kidney Disease (KNOW-CKD). The primary outcome was a composite of non-fatal cardiovascular events or all-cause mortality. Secondary outcomes included fatal and non-fatal cardiovascular events, all-cause mortality, and a composite kidney outcome of ≥ 50% decline in estimated glomerular filtration rate from baseline or the onset of end-stage kidney disease. There were 1088 (61%) men and 692 (39%) women in the study cohort. The proportion of smokers was significantly higher in men (24% vs. 3%). During 8430 person-years of follow-up, 201 primary outcome events occurred: 144 (13%) in men and 57 (8%) in women, with corresponding incidence rates of 2.9 and 1.7 per 100 person-years, respectively. In multivariable Cox models, men were associated with a 1.58-fold (95% CI 1.06–2.35) higher risk of composite outcome. Propensity score matching analysis revealed similar findings (HR 1.81; 95% CI 1.14–2.91). Risk of all-cause mortality was significantly higher in men of the matched cohort. However, there was no difference in the risk of CKD progression. In the subgroup with coronary artery calcium (CAC) measurements, men had a higher likelihood of CAC progression. In Korean CKD patients, men were more likely to experience adverse cardiovascular events and death than women.

Kidney tubular cell death induced by transforming growth factor-β1 (TGF-β1) is known to contribute to diabetic nephropathy, a major complication of diabetes. Caspase-3-dependent apoptosis and caspase-1-dependent pyroptosis are also involved in tubular cell death under diabetic conditions. Recently, ferroptosis, an atypical form of iron-dependent cell death, was reported to cause kidney disease, including acute kidney injury. Ferroptosis is primed by lipid peroxide accumulation through the cystine/glutamate antiporter system Xc− (xCT) and glutathione peroxidase 4 (GPX4)-dependent mechanisms. The aim of this study was to evaluate the role of ferroptosis in diabetes-induced tubular injury. TGF-β1-stimulated proximal tubular epithelial cells and diabetic mice models were used for in vitro and in vivo experiments, respectively. xCT and GPX4 expression, cell viability, glutathione concentration, and lipid peroxidation were quantified to indicate ferroptosis. The effect of ferroptosis inhibition was also assessed. In kidney biopsy samples from diabetic patients, xCT and GPX4 mRNA expression was decreased compared to nondiabetic samples. In TGF-β1-stimulated tubular cells, intracellular glutathione concentration was reduced and lipid peroxidation was enhanced, both of which are related to ferroptosis-related cell death. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, alleviated TGF-β1-induced ferroptosis. In diabetic mice, kidney mRNA and protein expressions of xCT and GPX4 were reduced compared to control. Kidney glutathione concentration was decreased, while lipid peroxidation was increased in these mice, and these changes were alleviated by Fer-1 treatment. Ferroptosis is involved in kidney tubular cell death under diabetic conditions. Ferroptosis inhibition could be a therapeutic option for diabetic nephropathy.

BACKGROUNDS: Chronic kidney disease is a growing global health problem. Psychosocial stress has been found to induce changes in biological processes and behavioral patterns that increase risks of cardiovascular and metabolic diseases. However, the association between psychosocial stress and kidney function is not well understood. OBJECTIVE: To evaluate the association between psychosocial stress and kidney function decline. DESIGN: In this prospective cohort study, psychosocial distress was assessed using the psychosocial well-being index short-form (PWI-SF). PARTICIPANTS: Data of a total of 7246 participants were retrieved from a community-based cohort (Korean Genome and Epidemiology Study). MAIN MEASURES: The rate of estimated glomerular filtration rate (eGFR) decline was calculated for each individual. Rapid eGFR decline was defined as a decrease of ≥ 3 mL/min/1.73 m(2) per year. The presence of kidney disease was defined as eGFR < 60 mL/min/1.73 m(2) at baseline or proteinuria of higher than trace levels from two consecutive urine test results. KEY RESULTS: A total of 7246 participants were analyzed. The mean eGFR was 92.1 ± 14.0 mL/min/1.73 m(2). Rapid eGFR decline was observed in 941 (13.0%) participants during a median follow-up of 11.7 years. When the participants were categorized into tertiles according to PWI-SF score, rapid eGFR decline was more prevalent in the group with the highest PWI-SF score (15.8%) than in the group with the lowest score (12.2%). Multivariate logistic regression analysis revealed that the risk of rapid eGFR decline was significantly increased in the tertile group with the highest PWI-SF score compared to the lowest group (odds ratio, 1.35; 95% confidence interval, 1.15–1.59). This association was maintained even after adjusting for confounding variables and excluding participants with kidney disease. CONCLUSIONS: Higher levels of psychosocial distress were closely associated with an increased risk of rapid kidney function decline. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-020-06573-9.

Introduction: We hypothesize that remote patient monitoring (RPM) for automated peritoneal dialysis (APD) and feedback could enhance patient self-management and improve outcomes. The aim of this study was to evaluate the efficacy of RPM-APD compared to traditional APD (T-APD) without RPM. Methods: In this multicenter, randomized controlled trial, patients on APD were randomized to T-APD (n = 29) or RPM-APD (n = 28) at 12 weeks and followed until 25 weeks. Health-related quality of life (HRQOL), patient and medical staff satisfaction with RPM-APD, and dialysis-related outcomes were compared between the 2 groups. Results: We found no significant differences in HRQOL scores at the time of enrollment and randomization between RPM-APD and T-APD. At the end of the study, the RPM-APD group showed better HRQOL for the sleep domain (p = 0.049) than the T-APD group and the T-APD group showed better HRQOL for the sexual function domain (p = 0.030) than the RPM-APD group. However, we found no significant interactions between the time and groups in terms of HRQOL. Different HRQOL domains significantly improved over time in patients undergoing RPM-APD (effects of kidney disease, p = 0.025) and T-APD (burden of kidney disease, p = 0.029; physical component summary, p = 0.048). Though medical staff satisfaction with RPM-APD was neutral, most patients were quite satisfied with RPM-APD (median score 82; possible total score 105 on 21 5-item scales) and the rating scores were maintained during the study period. We found no significant differences in dialysis adherence, accuracy, adequacy, overhydration status, blood pressure, or the number of unplanned visits between the 2 groups. Discussion/Conclusion: Although HRQOL and dialysis-related outcomes were comparable between RPM-APD and T-APD, RPM-APD was positive in terms of patient satisfaction. Further long-term and large-scale studies will be required to determine the efficacy of RPM-APD. Trial Registration: CRIS identifier: KCT0003390, registered on December 14, 2018 – retrospectively registered, https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=12348.

Background : The effect of fluid balance on outcomes in elderly patients with acute kidney injury (AKI) requiring continuous renal-replacement therapy (CRRT) is not explained well. We investigated outcomes according to cumulative fluid balance (CFB) in elderly patients with AKI undergoing CRRT. Methods : A total of 607 patients aged 65 years or older who started CRRT due to AKI were enrolled and stratified into two groups (fluid overload [FO] vs. no fluid overload [NFO]) based on the median CFB value for 72 hours before CRRT initiation. Propensity score-matching analysis was performed. Results : The median age of included patients was 73.0 years and 60.0% of the population was male. The median 72-hour CFB value was 2,839.0 mL. The overall cumulative survival and 28-day survival rates were lower in the FO group than in the NFO group (P < 0.001 for both) and remained so after propensity score-matching. Furthermore, patients in the FO group demonstrated a higher overall mortality risk after adjustment for age, sex, systolic blood pressure, Charlson comorbidity index, Acute Physiology and Chronic Health Evaluation II score, serum albumin, creatinine, diuretic use, and mechanical ventilation status (hazard ratio, 1.38; 95% confidence interval, 1.13 to 1.89; P < 0.001). Among survivors, both the duration of CRRT and the total duration of hospitalization from CRRT initiation showed no difference between the FO and NFO groups. Conclusion : A higher CFB value is associated with an increased risk of mortality in elderly patients with AKI requiring CRRT.

Objective To investigate the relationship between endogenous estrogen exposure and renal function, the association of female reproductive life span duration (RLD) and chronic kidney disease (CKD) was analyzed in postmenopausal women. Patients and Methods Data were retrieved from the Korean Genome and Epidemiology Study, which was constructed from May 1, 2001, through December 25, 2017. A total of 50,338 and 3155 postmenopausal women were each included in the cross-sectional and longitudinal analyses. The RLD was determined by subtracting the age at menarche from the age at menopause. Participants were grouped into RLD quartiles. Participants with estimated glomerular filtration rates less than 60 mL/min/1.73 m2 were regarded to have CKD. Results In the cross-sectional analysis, mean ± SD age and estimated glomerular filtration rate were 56.3±4.9 years and 93.1±13.6 mL/min/1.73 m2, respectively. Mean ± SD RLD was 34.2±4.0 years. A total of 765 of 50,338 (1.52%) women were found to have CKD. Logistic regression analysis revealed that the odds ratio for CKD was lower in groups with longer RLDs as compared with the shortest RLD group. In longitudinal analysis, postmenopausal women with normal kidney function were followed up for 9.7 years and incident CKD occurred in 221 of 3155 (7.00%) participants. Cox analysis revealed that the risk for CKD development was significantly lower in longer RLD groups. This finding was significant even after adjustments for confounding factors. Conclusion The risk for CKD was lower in women with longer RLDs. The amount of endogenous estrogen exposure could be a determining factor for renal function in postmenopausal women.

Sarcopenia, which is characterized by muscle mass and physical performance, is closely associated with morbidities and mortality, especially among the elderly. However, the effect of physical performance on chronic kidney disease (CKD) development is not yet fully elucidated. A total of 30,871 adults aged 66 years with preserved renal function who underwent health screening examinations were evaluated. Physical performance was assessed using a 3-m timed up and go (TUG) test and the one-leg stand (OLS) test. The primary outcome was the development of CKD, defined as at least two consecutive measurements of estimated glomerular filtration rate < 60 mL/min/1.73 m2. The rates of mortality and incident CKD development were significantly elevated with increases in TUG test scores but not in OLS scores. In the Cox hazards model, the highest TUG test score tertile was associated with an increased risk for CKD development (hazard ratio, 1.23; 95% confidence interval, 1.10-1.38) compared with the lowest tertile. No significant relationship was observed between OLS score and incident CKD risk. Poor physical performance, assessed using the TUG test, was related to an increased risk of CKD development.

Background : The aim of this study was to compare the effect of anemia on clinical outcomes according to age in patients with end-stage renal disease (ESRD). Methods : A total of 3,409 patients from the Clinical Research Center for ESRD were included and divided into three groups by age: age < 40 (n = 488), 40 ≤ age < 60 (n = 1,650), and age ≥ 60 (n = 1,271). We compared overall and cardiovascular mortality, and all-cause and cardiovascular hospitalization according to mean hemoglobin (Hb) concentration. Results : Among participants ≥ 60 years of age, the Hb < 10 g/dL group had greater all-cause mortality (adjusted hazard ratio [HR], 2.098; 95% confidence interval [CI], 1.567-2.808; P < 0.001) than the 10 ≤ Hb < 12 g/dL group, whereas among participants < 40 years of age, the Hb ≥ 12 g/dL group had greater mortality than the 10 ≤ Hb < 12 g/dL group. Moreover, in participants ≥ 60 years of age, the HR for all-cause hospitalization for the Hb < 10 g/dL group was significantly greater than that of the 10 ≤ Hb < 12 g/dL group (HR, 1.472; 95% CI, 1.057-2.051; P = 0.022), whereas it was significantly lower in the Hb ≥ 12 g/dL group (HR, 0.544; 95% CI, 0.362-0.820; P = 0.004) However, among participants < 40 years of age, the incidence of all-cause hospitalization did not differ according to the Hb concentration (HR, 1.273; 95% CI, 0.814-1.991; P = 0.290 for the Hb < 10 g/dL group; reference, 10 ≤ Hb < 12 g/dL; HR, 0.787; 95% CI, 0.439-1.410; P = 0.265 for Hb ≥ 12 g/dL group). Conclusion : The impact of anemia on mortality was more significant in elderly ESRD patients. Strict monitoring and management of anemia should be required for elderly ESRD patients.

Background Obesity, a known risk factor for chronic kidney disease (CKD), is generally assessed using body mass index (BMI). However, BMI may not effectively reflect body composition, and the impact of muscle‐to‐fat (MF) mass balance on kidney function has not been elucidated. This study evaluated the association between body muscle and fat mass balance, represented as the MF ratio, and incident CKD development. Methods Data were retrieved from a prospective community‐based cohort study (Korean Genome and Epidemiology Study). Muscle and fat mass were measured using multifrequency bioelectrical impedance analysis. The study endpoint was incident CKD (estimated glomerular filtration rate

Introduction In patients with chronic kidney disease (CKD), studies investigating the association between smoking and deterioration of kidney function are scarce. Aims and Methods We analyzed data for 1,951 patients with an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) from 2011 to 2016. Patients were categorized by smoking load. Primary outcome was a composite of a ≥50% reduction in eGFR, initiation of dialysis, or kidney transplantation. Results There were 967 never-smokers and 369, 276, and 339 smokers who smoked Conclusions These findings suggest potentially harmful effects of the degree of exposure to smoking on the progression of CKD. Implications Among patients with CKD, there has been lack of studies on the association between smoking and CKD progression and studies to date have yielded conflicting results. In this prospective cohort study involving Korean CKD patients, smoking was associated with significantly higher risk of worsening kidney function. Furthermore, the risk of adverse kidney outcome was incrementally higher as smoking pack-years were higher. As the duration of smoking cessation increased, the hazard ratios for adverse kidney outcome were attenuated, suggesting that quitting smoking may be a modifiable factor to delay CKD progression.

Background Vibrio vulnificus infection is a rare but fatal foodborne illness. Here, we report a case of Vibrio vulnificus peritonitis followed by severe septicemia in a patient undergoing continuous ambulatory peritoneal dialysis (CAPD) who was treated with hemoperfusion using polymyxin B immobilized fiber. Case presentation A 63-year-old man undergoing CAPD was admitted to the emergency room due to general weakness, fever, and abdominal pain with hazy dialysate. Two days before admission, he had eaten raw fish. Initial laboratory tests including peritoneal fluid analysis suggested peritonitis. Despite empirical intraperitoneal antibiotic treatment, his fever did not subside, and multiple vesicles on the extremities newly appeared. The result of initial peritoneal fluid culture and blood cultures reported Vibrio vulnificus as the most likely causative pathogen. Hemoperfusion with polymyxin B immobilized fiber was performed to control gram-negative bacterial septicemia with antibiotics targeting the pathogenic organism. The patient recovered completely and was discharged without complications. Discussion and conclusion Suspicion of Vibrio vulnificus infection in susceptible immunocompromised patients is important for early diagnosis and prompt management. Peritonitis should be noted as a clinical manifestation of Vibrio vulnificus infection in CAPD patients, and polymyxin B hemoperfusion along with proper antibiotics could be considered as a treatment option.

Background : : Higher statin intensity is associated with a lower risk of mortality in patients with cardiovascular disease. However, little is known about the relationship between statin intensity and chronic kidney disease (CKD) progression. Methods : : We studied whether statin intensity affects kidney function decline in 1,073 patients from the Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease. The participants were classified based on statin intensity as low, moderate, and high. The study endpoint was CKD progression (composite of doubling of serum creatinine, ≥ 50% decrease in estimated glomerular filtration rate [eGFR] from baseline, or end-stage renal disease). Results : : The mean age was 56.0 ± 11.4 years, and 665 (62.0%) participants were male. The mean eGFR was 51.7 ± 26.7 mL/min/1.73 m2; there were no differences in baseline eGFR among statin intensity groups. During the median follow-up of 39.9 (25.4-61.6) months, 255 (23.8%) patients reached the study endpoint. In multivariable Cox model after adjustment of confounders, the hazard ratios (95% confidence interval) for adverse kidney outcome were 0.97 (0.72-1.30) and 1.15 (0.60-2.20) in moderate and high statin intensity groups, respectively, compared with the low intensity group. In addition, no significant association was observed in subgroups stratified by age, sex, eGFR, and atherosclerotic cardiovascular disease risk scores. Conclusion : : We did not observe any significant association between intensity of statin therapy and progression of CKD. Long-term kidney outcomes may not be affected by statin intensity.

Objective To examine the association between income level and incident chronic kidney disease (CKD) in adults with normal baseline kidney function. Patient and Methods We studied the association between income level categorized into deciles and incident CKD in a national cohort comprised of 7,405,715 adults who underwent National Health Insurance Service health examinations during January 1, 2009, to December 31, 2015, with baseline estimated glomerular filtration rates (eGFRs) ≥60 mL/min/1.73 m2. Incident CKD was defined as de novo development of eGFR Results During a median follow-up of 4.8 years, there were 122,032 of 7,405,715 (1.65%) and 55,779 of 7,405,715 (0.75%) incident CKD events based on model 1 and 2 definitions, respectively. Compared with income levels in the sixth decile, there was an inverse association between lower income level and higher risk for CKD up to the fourth decile, above which no additional reduction (model 1) or slightly higher risk for CKD (model 2) was observed at higher income levels. The multivariable-adjusted hazard ratios from the lowest to fourth deciles were 1.30 (95% CI, 1.26-1.33), 1.16 (95% CI, 1.13-1.19), 1.07 (95% CI, 1.05-1.10), and 1.06 (95% CI, 1.03-1.09) in model 1 and 1.32 (95% CI, 1.27-1.37), 1.18 (95% CI, 1.14-1.22), 1.08 (95% CI, 1.04-1.13), and 1.05 (95% CI, 1.01-1.09) in model 2, respectively. These associations persisted across various subgroups of age, sex, and comorbidity status. Conclusion In this large nationwide cohort, lower income levels were associated with higher risk for incident CKD.

Objective To assess the association of alcohol consumption with chronic kidney disease (CKD) progression in patients with CKD. Patients and Methods The KoreaN cohort study for Outcome in patients with CKD (KNOW-CKD) is a prospective observational study that included detailed questionnaires regarding alcohol consumption. The 1883 individuals with CKD were enrolled from April 1, 2011, through February 28, 2016, and followed until May 31, 2017. Using a questionnaire, alcohol consumption pattern was classified according to the amount of alcohol per occasion (none, moderate, or binge) or drinking frequency (none, occasional, or regular). The primary endpoint was a composite of 50% or greater decline in estimated glomerular filtration rate (eGFR) from the baseline level or end-stage renal disease. Results During a follow-up of 5555 person-years (median, 2.95 years), the primary outcome occurred in 419 patients. Unadjusted cause-specific hazards model showed that the risk of the primary outcome was lower in drinkers than in non-drinkers. However, a fully adjusted model including eGFR and proteinuria yielded a reverse association. Compared with non-drinking, regular and occasional binge drinking were associated with a 2.2-fold (95% CI, 1.38-3.46) and a 2.0-fold (95% CI, 1.33-2.98) higher risk of CKD progression, respectively. This association was particularly evident in patients who had decreased kidney function and proteinuria. There was a significant interaction between alcohol consumption and eGFR for CKD progression. The slopes of eGFR decline were steeper in binge drinkers among patients with eGFR less than 60 mL/min/1.73 m2. Conclusions Heavy alcohol consumption was associated with faster progression of CKD.

Background: Although arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis (HD), the association between vascular access types and quality of life is not well-known. We investigated the relationships between HD vascular access types and all-cause mortality, health-related quality of life (HRQOL) and the degree of depression in a large prospective cohort. Methods: A total of 1461 patients who newly initiated HD were included. The initial vascular access types were classified into AVF, arteriovenous graft (AVG), and central venous catheter (CVC). The primary outcomes were all-cause mortality and HRQOL and depression. The secondary outcome was all-cause hospitalization. Kidney Disease Quality of Life Short Form 36 (KDQOL-36) and Beck’s depression inventory (BDI) scores were measured to assess HRQOL and depression. Results: Among 1461 patients, we identified 314 patients who started HD via AVF, 76 via AVG, and 1071 via CVC. In the survival analysis, patients with AVF showed significantly better survival compared with patients with other accesses (p

Objective: Obesity is an established risk factor for kidney damage. In this study, we explored the long-term association of changes in body mass index (BMI) over time with incident chronic kidney disease (CKD).Methods: For this analysis, 5,393 middle-aged adults without comorbidities in the Korean Genome and Epidemiology Study (KoGES) were included. Group-based trajectory modeling was used to determine the patterns of BMI change (decreasing, stable, and increasing BMI) between baseline and year 4. The primary outcome was the subsequent development of CKD from year 4. A multivariable Cox proportional hazards model was constructed to determine the risk of incident CKD according to BMI trajectories.Results: During 55,327 person-years, incident CKD occurred in 354 (6.5%) participants; 6.0, 6.1, and 7.8 per 1,000 person-years across the trajectories, respectively (P = 0.005). In the multivariable-adjusted Cox proportional hazards model, the increasing BMI trajectory was associated with a 1.4-fold [hazard ratio (HR), 1.41; 95% CI, 1.06–1.87] a higher risk of incident CKD compared with stable BMI trajectory. This association was stronger for overweight and obese individuals. The HRs for CKD development in these two groups were 1.6 (95% CI, 1.06–1.87) and 2.2 (95% CI, 1.40–3.48), respectively. While the increasing BMI group was gaining weight, there were concomitant increases in blood pressure, insulin resistance, serum concentrations of total cholesterol, triglyceride, and high-sensitivity C-reactive protein (hs-CRP), and fat mass, but high-density lipoprotein (HDL)-cholesterol level and muscle-to-fat (MF) ratio decreased.Conclusion: Weight gain is associated with an increased risk of incident CKD in healthy adults. This association is attributed to worsening metabolic profiles and increasing fat mass.

Background The function of high‐density lipoprotein can change from protective to proatherosclerotic under inflammatory conditions. Herein, we studied whether inflammation could modify the relationship between high‐density lipoprotein level and risk of adverse outcomes in patients with chronic kidney disease . Methods and Results In total, 1864 patients from the prospective KNOW‐CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) were enrolled. The main predictor was high‐density lipoprotein cholesterol (HDL‐C) level. Presence of inflammation was defined by hs‐CRP (high‐sensitivity C‐reactive protein) level of ≥1.0 mg/L. The primary outcome was extended major adverse cardiovascular events. During 9231.2 person‐years of follow‐up, overall incidence of the primary outcome was 15.8 per 1000 person‐years. In multivariable Cox analysis after adjusting for confounders, HDL‐C level was not associated with the primary outcome. There was a significant interaction between the inflammatory status and HDL‐C for risk of extended major adverse cardiovascular events ( P =0.003). In patients without inflammation, the hazard ratios (HRs) (95% CIs) for HDL‐C levels Conclusions The association between HDL‐C level and adverse cardiovascular outcomes showed reverse trends based on inflammation status in Korean patients with chronic kidney disease. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01630486.

Studies on the longitudinal temporal trend of blood pressure (BP) and its impact on kidney function are scarce. Here, we evaluated the association of dynamic changes in systolic blood pressure (SBP) over time with adverse kidney outcomes. We analyzed 1837 participants from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease). The main exposure was 3 distinct SBP trajectories determined by the latent class mixed model (decreasing, stable, and increasing) using 3 SBP measurements at 0, 6, and 12 months. The primary outcome was CKD progression, defined as a composite of halving estimated glomerular filtration rate from baseline value or onset of end-stage kidney disease. SBP declined from 144 to 120 mm Hg in the decreasing SBP trajectory group and rose from 114 to 136 mm Hg in the increasing trajectory group within 1 year. During 6576 person-years of follow-up (median, 3.7 years), the composite outcome occurred in 521 (28.4%) participants. There were fewer primary outcome events in the decreasing (30.6%) and stable (26.5%) SBP trajectory groups than in the increasing trajectory group (33.0%). In the multivariable-adjusted cause-specific hazards model, increasing SBP trajectory was associated with a 1.28-fold higher risk for adverse kidney outcome compared with stable SBP trajectory. However, the risk for the primary outcome did not differ between the decreasing and stable SBP trajectory groups. In this longitudinal CKD cohort study, compared with stable SBP trajectory, increasing SBP trajectory was associated with higher risk for adverse kidney outcome, whereas decreasing SBP trajectory showed similar risk.

In patients with kidney failure with replacement therapy (KFRT), optimizing anemia management in these patients is a challenging problem because of the complexities of the underlying diseases and heterogeneous responses to erythropoiesis-stimulating agents (ESAs). Therefore, we propose a ESA dose recommendation model based on sequential awareness neural networks. Data from 466 KFRT patients (12,907 dialysis sessions) in seven tertiary-care general hospitals were included in the experiment. First, a Hb prediction model was developed to simulate longitudinal heterogeneous ESA and Hb interactions. Based on the prediction model as a prospective study simulator, we built an ESA dose recommendation model to predict the required amount of ESA dose to reach a target hemoglobin level after 30 days. Each model's performance was evaluated in the mean absolute error (MAE). The MAEs presenting the best results of the prediction and recommendation model were 0.59 (95% confidence interval: 0.56-0.62) g/dL and 43.2 μg (ESAs dose), respectively. Compared to the results in the real-world clinical data, the recommendation model achieved a reduction of ESA dose (Algorithm: 140 vs. Human: 150 μg/month, P 0.001), a more stable monthly Hb difference (Algorithm: 0.6 vs. Human: 0.8 g/dL, P 0.001), and an improved target Hb success rate (Algorithm: 79.5% vs. Human: 62.9% for previous month's Hb 10.0 g/dL; Algorithm: 95.7% vs. Human:73.0% for previous month's Hb 10.0-12.0 g/dL). We developed an ESA dose recommendation model for optimizing anemia management in patients with KFRT and showed its potential effectiveness in a simulated prospective study.

Acute kidney injury (AKI) is a severe complication of coronavirus disease (COVID-19) that negatively affects its outcome. Concern had been raised about the potential effect of renin–angiotensin–aldosterone system (RAAS) blockades on renal outcomes in COVID-19 patients. However, the association between RAAS blockade use and incident AKI in COVID-19 patients has not been fully understood. We investigated the association between RAAS blockade exposure and COVID-19-related AKI in hospitalized patients through meta-analysis. Electronic databases were searched up to 24th December 2020. Summary estimates of pooled odds ratio (OR) of COVID-19-related AKI depending on RAAS blockade exposure were obtained through random-effects model. The random-effect meta-analysis on fourteen studies (17,876 patients) showed that RAAS blockade use was significantly associated with increased risk of incident AKI in hospitalized COVID-19 patients (OR 1.68; 95% confidence interval 1.19–2.36). Additional analysis showed that the association of RAAS blockade use on COVID-19-related AKI remains significant even after stratification by drug class and AKI severity. RAAS blockade use is significantly associated with the incident AKI in hospitalized COVID-19 patients. Therefore, careful monitoring of renal complications is recommended for COVID-19 patients with recent RAAS blockade use due to the potential risk of AKI.

Background The risk of delayed AKI (AKI development beyond the perioperative period) in patients undergoing colorectal surgery is greater than that in patients undergoing other major operations. However, the characteristics of and risk factors for delayed AKI are unclear. Methods We investigated 683 patients who underwent colorectal surgery with intestinal resection at a single tertiary hospital. All patients were followed-up for a year postoperatively. The primary outcome was the development of AKI during follow-up. Results AKI occurred in 177 (25.9%) during the first postoperative year. Patients who developed AKI were significantly older, showed a lower body mass index, and significantly lower preoperative hemoglobin and serum albumin levels. AKI occurred most commonly during the first 3 months postoperatively. However, AKI occurred persistently even after this initial period. Older age, lower preoperative serum albumin levels, and late ostomy closure were independently associated with a higher risk of delayed AKI. Conclusion AKI commonly occurs beyond the perioperative period. Careful risk stratification and modification of risk factors may prevent delayed AKI in patients undergoing colorectal cancer surgery.

Background Complement activation has been highlighted in immunoglobulin (Ig) A nephropathy pathogenesis. However, whether the complement system can affect the downstream phenotype of IgA nephropathy remains unknown. Herein, we investigated the association of mesangial C3 deposition with the Oxford classification and their joint effects on worsening kidney function. Methods We investigated 453 patients with biopsy-proven IgA nephropathy. C3 deposition was defined as an immunofluorescence intensity of C3 ≥2+ within the mesangium. The subjects were classified according to the combination of C3 deposition and Oxford classification lesions. The primary endpoint was a composite of ≥30% decline in the estimated glomerular filtration rate or an increase in proteinuria ≥3.5 g/g during follow-up. Results Among the Oxford classification lesions, mesangial hypercellularity (M1), segmental glomerulosclerosis (S1) and tubulointerstitial fibrosis (T1–2) and crescentic lesion significantly correlated with C3 deposition. During a median follow-up of 33.0 months, the primary endpoint occurred more in patients with M1, S1, T1–2 and mesangial C3 deposition than in those without. In individual multivariable-adjusted Cox analyses, the presence of M1, S1, T1–2 and C3 deposition was significantly associated with higher risk of reaching primary endpoint. In the combined analyses of C3 deposition and the Oxford classification lesions, the hazard ratios for the composite outcome were significantly higher in the presence of C3/M1, C3/S1 and C3/crescent than in the presence of each lesion alone. Conclusions Complement deposition can strengthen the significance of the Oxford classification, and the presence of both components portends a poorer prognosis in IgA nephropathy.

This study aimed to compare health-related quality of life (HRQOL) over time in patients initiating hemodialysis (HD) or peritoneal dialysis (PD). A total of 989 incident patients starting HD or PD were included from a prospective nationwide cohort study. HRQOL was assessed 3, 12, and 24 months after the start of dialysis. The scores of questionnaires were adjusted for clinical and socioeconomic parameters. The adjusted three months scores of patients on PD showed better HRQOL in eight end-stage renal disease (ESRD), three physical component summary and one mental component summary domains compared with patients on HD. Both patients on HD and PD experienced significant decreases in different HRQOL domains over two years and the degree of changes in HRQOL over time was not different between dialysis modality. However, the scores of three (effects of kidney disease, burden of kidney disease, and dialysis staff encouragement, all P P

Background/Aims: Patients with chronic kidney disease (CKD) have been found to show markedly increased rates of end-stage renal disease, major adverse car diovascular and cerebrovascular events (MACCEs), and mortality. Therefore, new biomarkers are required for the early detection of such clinical outcomes in pa tients with CKD. We aimed to determine whether the level of circulating renalase was associated with CKD progression, MACCEs, and all-cause mortality, using data from a prospective randomized controlled study, Kremezin STudy Against Renal disease progression in Korea (K-STAR; NCT 00860431). Methods: A retrospective analysis of the K-STAR data was performed including 383 patients with CKD (mean age, 56.4 years; male/female, 252/131). We measured circulating renalase levels and examined the effects of these levels on clinical outcomes. Results: The mean level of serum renalase was 75.8 ± 34.8 μg/mL. In the multi variable analysis, lower hemoglobin levels, higher serum creatinine levels, and diabetes mellitus were significantly associated with a higher renalase levels. Over the course of a mean follow-up period of 56 months, 25 deaths and 61 MACCEs occurred. Among 322 patients in whom these outcomes were assessed, 137 adverse renal outcomes occurred after a mean follow-up period of 27.8 months. Each 10- μg/mL increase in serum renalase was associated with significantly greater haz ards of all-cause mortality and adverse renal outcomes (hazard ratio [HR] = 1.112, p = 0.049; HR = 1.052, p = 0.045). However, serum renalase level was not associated with the rate of MACCEs in patients with CKD. Conclusions: Our results indicated that circulating renalase might be a predictor of mortality and adverse renal outcomes in patients with CKD.

Background: Urine osmolality indicates the ability of the kidney to concentrate the urine and reflects the antidiuretic action of vasopressin. However, results about the association between urine osmolality and adverse renal outcomes in chronic kidney disease (CKD) are conflicting. We investigated the association between urine osmolality and adverse renal outcomes in a nationwide prospective CKD cohort. Methods: A total of 1,999 CKD patients were categorized into 3 groups according to their urine osmolality tertiles. Primary outcome was a composite of 50% decline in the estimated glomerular filtration rate (eGFR), initiation of dialysis, or kidney transplantation. Results: During a mean follow-up of 35.2 ± 19.0 months, primary outcome occurred in 432 (21.6%) patients; 240 (36.4%), 162 (24.3%), and 30 (4.5%) in the lowest, middle, and highest tertiles, respectively. Low urine osmolality was independently associated with a greater risk of CKD progression (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.12–2.59). This association was particularly evident in patients with CKD stages 3–4 (per 10 mosm/kg decrease; HR, 1.02; 95% CI, 1.00–1.03). Adding urine osmolality to a base model with conventional factors significantly increased the ability to predict CKD progression (C-statistics, 0.86; integrated discrimination improvement [IDI], 0.021; both p < 0.001). However, adding both urine osmolality and eGFR did not further improve the predictive ability compared with the addition of eGFR only (C-statistics, p = 0.29; IDI, p = 0.09). Conclusions: Low urine osmolality was an independent risk factor for adverse renal outcomes in CKD patients, but its predictive ability did not surpass eGFR. Thus, kidney function should be considered while interpreting the clinical significance of urine osmolality.

Background: Corticosteroids can be used to treat IgA nephropathy (IgAN). However, responsiveness to these drugs is highly variable and unpredictable. Corticosteroids act by binding glucocorticoid receptors (GCRs). Therefore, we evaluated the association between GCR expression and responsiveness to corticosteroid treatment in IgAN. Methods: We screened 78 IgAN patients receiving steroid treatment between 2010 and 2016. Of these, 33 patients met study inclusion criteria. Glomerular GCR expression was assessed by real-time polymerase chain reaction. Complete remission (CR) and partial remission (PR) were defined as a spot urine protein-to-creatinine ratio (UPCR) of Results: The mean age of study patients was 43.9 ± 11.6 years (25 males and 8 females). All 33 patients responded to steroid treatment; CR and PR occurred in 14 (42.4%) and 18 (54.5%) patients, respectively. One patient did not achieve PR, but proteinuria was decreased after treatment. There were no significant differences in baseline eGFR and proteinuria between CR and non-CR groups. GCR mRNA expression was significantly higher in the CR group compared to that in the non-CR group. Immunohistochemistry confirmed higher GCR expression in the CR group. During a median follow-up of 20.6 months, 1 (7.1%) patient in the CR group had disease progression, as compared to 8 (42.1%) patients in non-CR group (p = 0.03). Conclusion: This study suggests that responsiveness to corticosteroid may differ depending on the degree of glomerular GCR expression in IgAN.

Vitamin D deficiency is associated with renal progression in chronic kidney disease. Moreover, improvement of clinical outcomes after vitamin D supplementation has been reported in the diabetic and chronic kidney disease population.We investigated the association between renal hyperfiltration (RHF) and vitamin D status in a relatively healthy population.Data were retrieved from the Korean NHANES, a nationwide population-based cross-sectional study from 2008 to 2015. Overall, 33,210 subjects with normal renal function were included in the final analysis. Severe vitamin D deficiency was defined as serum 25-hydroxyvitamin D concentration10 ng/mL. RHF was defined as estimated glomerular filtration rate with residual in the95th percentile after adjustment for age, sex, height, weight, and history of hypertension or diabetes.The mean ± SD age of subjects was 48.1 ± 15.9 y, and the number of women was 18,779 (56.5%). Estimated glomerular filtration rate was negatively associated with serum 25-hydroxyvitamin D concentrations in multivariable linear regression analysis (β: -0.02; 95% CI: -0.02, -0.01; P 0.001). Furthermore, 1637 (4.9%) subjects were categorized into the RHF group, and the prevalence of RHF was significantly higher in the severe vitamin D deficiency group than in the sufficiency group (5.8% compared with 5.0%, P 0.001). In a multivariable logistic regression model, severe vitamin D deficiency was a significant risk factor for RHF (OR: 2.41; 95% CI, 1.72, 3.43; P 0.001).Severe vitamin D deficiency is significantly associated with increasing prevalence of RHF in a relatively healthy adult population.

The optimal low-density lipoprotein cholesterol (LDL-C) level to prevent cardiovascular disease in chronic kidney disease (CKD) patients remains unknown. This study aimed to explore the association of LDL-C levels with adverse cardiovascular and kidney outcomes in Korean CKD patients and determine the validity of "the lower, the better" strategy for statin intake.A total of 1886 patients from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD) were included. Patients were classified into four LDL-C categories:70, 70-99, 100-129, and ≥130 mg/dL. The primary outcome was extended major adverse cardiovascular events (eMACEs). Secondary outcomes included all-cause mortality, and CKD progression. During the follow-up period, the primary outcome events occurred in 136 (7.2%) patients (16.9 per 1000 person-years). There was a graded association between LDL-C and the risk of eMACEs. The hazard ratios (95% confidence intervals) for LDL-C categories of 70-99, 100-129, and ≥130 mg/dL were 2.06 (1.14-3.73), 2.79 (1.18-6.58), and 4.10 (1.17-14.3), respectively, compared to LDL-C70 mg/dL. Time-varying analysis showed consistent findings. The predictive performance of LDL-C for eMACEs was affected by kidney function. Higher LDL-C levels were also associated with significantly higher risks of CKD progression. However, LDL-C level was not associated with all-cause mortality.This study showed a graded relationship between LDL-C and the risk of adverse cardiovascular outcome in CKD patients. The lowest risk was observed with LDL-C70 mg/dL, suggesting that a lower LDL-C target may be acceptable.

Many current guidelines on optimal target blood pressure (BP) for chronic kidney disease (CKD) patients are largely based on studies in diabetic and hypertensive patients. However, there have been few studies in patients with glomerular diseases. We retrospectively studied the longitudinal association between BP and CKD progression in 1,066 biopsy-proven patients diagnosed with primary glomerular diseases, including IgA nephropathy, membranous nephropathy (MN), and focal segmental glomerulosclerosis (FSGS), between 2005 and 2017. The main predictor was time-updated systolic blood pressure (SBP) at every clinic visit. The primary outcome was a composite one including ≥ 50% decrease in estimated glomerular filtration rate (eGFR) from the baseline, and end-stage kidney disease (ESKD). During 5009 person-years of follow-up, the primary outcome occurred in 157 (14.7%) patients. In time-varying Cox model, the adjusted hazard ratios (HRs) (95% confidence interval (CI)) for the primary outcome were 1.48 (0.96–2.29), 2.07 (1.22–3.52), and 2.53 (1.13–5.65) for SBP of 120–129, 130–139, and ≥ 140 mmHg, respectively, compared with SBP

Background Soluble urokinase‐type plasminogen activator receptor (suPAR) is associated with cardiovascular risks and poor renal outcomes. However, whether elevated suPAR levels are associated with 24‐hour blood pressure patterns or kidney disease progression in patients with chronic kidney disease (CKD) is unclear. Methods and Results A total of 751 patients with CKD stage 1 to 5 were recruited from CMERC‐HI (Cardiovascular and Metabolic Disease Etiology Research Center–High Risk) cohort study (2013–2018). The relationship of serum suPAR levels to 24‐hour blood pressure parameters and CKD progression was analyzed. The median serum suPAR level was 1439.0 (interquartile range, 1026.2–2150.1) pg/mL, and the mean estimated glomerular filtration rate was 52.8±28.5 mL/min per 1.73 m 2 at baseline. Patients with higher suPAR levels had significantly higher levels of office, 24‐hour, daytime, and nighttime systolic blood pressure and nighttime diastolic blood pressure than those with lower suPAR levels. The highest suPAR tertile was associated with an increased risk of a reverse dipping pattern (odds ratio, 2.93; 95% CI, 1.27–6.76; P =0.01). During a follow‐up of 43.2 (interquartile range, 27.0–55.6) months, the CKD progression occurred in 271 (36.1%) patients. The highest suPAR tertile was significantly associated with higher risk of CKD progression than the lowest tertile (hazard ratio [HR], 2.09; 95% CI, 1.37–3.21; P =0.001). When the relationship was reevaluated with respect to each dipping pattern (dipper, extreme dipper, nondipper, and reverse dipper), this association was consistent only in reverse dippers in whom the risk of CKD progression increased (HR, 1.43; 95% CI, 1.02–2.01; P =0.03) with every 1‐unit increase in serum suPAR levels. Conclusions Elevated suPAR levels are independently associated with CKD progression, and this association is prominent in reverse dippers.

The transtubular potassium gradient which reflects potassium secretion by the kidney through the cortical collecting duct, has not yet been tested as a surrogate marker of kidney function decline. Here, we investigate the relationship between the transtubular potassium gradient and chronic kidney disease (CKD) progression. We studied 1672 patients from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort. The transtubular potassium gradient was calculated using a standard equation. The study endpoint was CKD progression, defined as a composite of a ≥ 50% decrease in estimated glomerular filtration rate (eGFR) from baseline values or end-stage kidney disease. During a median follow-up of 4.1 years (7149 person-years), 441 participants reached the endpoint. In cause-specific competing risk analysis, the highest tertile was associated with a significantly lower risk of an adverse kidney outcome compared with the lowest tertile [hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55–0.97]. When the transtubular potassium gradient was treated as a continuous variable, an increase of 1 in the transtubular potassium gradient was associated with a 6% lower risk of CKD progression (95% CI, 0.90–0.99). This association was particularly evident in patients with an eGFR ≥ 45 mL/min/1.73 m2. A time-updated transtubular potassium gradient model showed similar results. The predictive performance of the transtubular potassium gradient was significantly less than that of the eGFR, but similar to that of proteinuria, serum bicarbonate, and urine osmolality. A higher transtubular potassium gradient is associated with a significantly lower risk of CKD progression, suggesting that it may offer insights into the prognosis of CKD.

Background and aims Decreased kidney function is an important risk factor for cardiovascular disease (CVD). However, assessing risk of CVD may be difficult when there is a gap between creatinine- and cystatin C-based estimated glomerular filtration rate (eGFR). We studied the association of the difference in eGFRs with major adverse cardiovascular events (MACE) in patients with chronic kidney disease (CKD). Methods This prospective cohort study was conducted in 2076 patients with CKD stages based on the KDIGO guideline (eGFR categories of G1: ≥90; G 2: 60–89; G3: 30–59; G4: 15–29; G5: Results During a median follow-up of 4.1 years, MACE occurred in 147 patients (incidence rate, 15.0 per 1000 patient-years). When patients were categorized into baseline eGFRdiff tertiles, the highest tertile was associated with a significantly higher risk of MACE (hazard ratio, 2.12; 95% confidence interval [CI], 1.28–3.51) than the lowest tertile when adjusted for eGFRcreat, eGFRcys, or eGFR based on both creatinine and cystatin C. Patients in the highest tertile had more baseline coronary artery calcification (CAC) than those in the lowest tertile (odds ratio [OR], 1.38; 95% CI, 1.03–1.86). In addition, 978 patients had data for both baseline and follow-up CAC at year 4. In this subgroup, baseline eGFRdiff was significantly associated with accelerated CAC progression (≥50/year) (OR, 1.03; 95% CI, 1.01–1.05). Conclusions A large positive difference between eGFRcreat and eGFRcys was associated with a higher risk of MACE and faster CAC progression in patients with CKD. Therefore, careful monitoring of CVD is needed for patients with a higher eGFRdiff.

Background Inflammation levels are lower in East Asians than in Western people. We studied the association between high‐sensitivity hs‐CRP (C‐reactive protein) and adverse outcomes in Korean patients with chronic kidney disease. Methods and Results We included 2018 participants from the KNOW‐CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) between April 2011 and February 2016. The primary outcome was a composite of extended major cardiovascular events (eMACE) or all‐cause mortality. The secondary end points were separate outcomes of eMACE, all‐cause death, and adverse kidney outcome. We also evaluated predictive ability of hs‐CRP for the primary outcome. The median hs‐CRP level was 0.60 mg/L. During the mean follow‐up of 3.9 years, there were 125 (6.2%) eMACEs and 80 (4.0%) deaths. In multivariable Cox analysis after adjustment of confounders, there was a graded association of hs‐CRP with the primary outcome. The hazard ratios for hs‐CRPs of 1.0 to 2.99 and ≥3.0 mg/L were 1.33 (95% CI, 0.87–2.03) and 2.08 (95% CI, 1.30–3.33) compared with the hs‐CRP of Conclusions In Korean patients with chronic kidney disease, the hs‐CRP level was low and significantly associated with higher risks of eMACEs and mortality. However, hs‐CRP did not associate with adverse kidney outcome, and the predictive performance of hs‐CRP was not strong. Registration URL: http://www.clinicaltrials.gov ; Unique identifier: NCT01630486.

BACKGROUND AND OBJECTIVES: Smoking is associated with vascular calcification and a higher risk of cardiovascular disease. In this study, we investigated the association of smoking dose and cessation with coronary artery calcification (CAC) in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From a nationwide, prospective cohort of Korean patients with CKD, 1914 participants were included. Prevalent CAC was defined as an Agatston score >0, using computed tomography. CAC progression was defined as ≥30%/yr increase in Agatston score at the 4-year follow-up examination in patients with baseline CAC. RESULTS: Prevalent CAC was observed in 952 (50%) patients. Compared with never smokers, former smokers had a similar prevalence ratio for CAC, but current smokers had a 1.25-fold higher prevalence ratio (95% confidence interval [95% CI], 1.10 to 1.42). Among former smokers, a lower smoking load of

Background The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium–glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials. Methods In DAPA-CKD, 4304 participants with a urinary albumin:creatinine ratio (UACR) ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 were randomized to dapagliflozin 10 mg once daily or placebo. Mean eGFR was 43.1 mL/min/1.73 m2 and median UACR was 949 mg/g (108 mg/mmol). Results Overall, 2906 participants (68%) had a diagnosis of T2D and of these, 396 had CKD ascribed to a cause other than diabetes. The most common causes of CKD after diabetes (n = 2510) were ischaemic/hypertensive nephropathy (n = 687) and chronic glomerulonephritis (n = 695), of which immunoglobulin A nephropathy (n = 270) was the most common. A total of 4174 participants (97%) were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 1882 (43.7%) diuretics, 229 (5.3%) mineralocorticoid receptor antagonists and 122 (2.8%) glucagon-like peptide 1 receptor agonists. In contrast to the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), the DAPA-CKD trial enrolled participants with CKD due to diabetes and to causes other than diabetes. The mean eGFR of participants in the DAPA-CKD trial was 13.1 mL/min/1.73 m2 lower than in CREDENCE, similar to that in the Finerenone in Reducing Kidney Failure and Disease Progression in DKD (FIDELIO-DKD) trial and the Study Of diabetic Nephropathy with AtRasentan (SONAR). Conclusions Participants with a wide range of underlying kidney diseases receiving renin–angiotensin system blocking therapy have been enrolled in the DAPA-CKD trial. The trial will examine the efficacy and safety of dapagliflozin in participants with CKD Stages 2–4 and increased albuminuria, with and without T2D.

Background and Aims High-sensitivity C-reactive protein (hs-CRP) level is lower in East Asians than in the Western people and its clinical significance needs to be further explored. We aimed to investigate whether hs-CRP could function as a biomarker in Korean CKD patients. Method We studied the association of hs-CRP with adverse clinical outcomes in 2,018 patients from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). The primary outcome was a composite of extended major cardiovascular events (MACE) or all-cause mortality. Extended MACE (eMACE) included non-fatal cardiovascular events, symptomatic arrhythmia, and cardiac death. The secondary endpoints were separate outcome of eMACE, all-cause death, and adverse kidney outcome. We also evaluated predictive ability of hs-CRP for the primary outcome. Results The median hs-CRP level was 0.60 mg/L (IQR 0.2-1.7), and the mean eGFR was 53.6 ml/min/1.73 m2. During the mean follow-up of 3.9 years, there were 125 (6.2%) eMACEs and 80 (4.0%) deaths. The primary composite outcome occurred more frequently in patients with higher hs-CRP level than in those with lower hs-CRP level. In multivariable Cox analysis after adjustment of confounders, there was a graded association of hs-CRP with the primary outcome. The HRs (95% CI) for hs-CRP of 1.0 to 2.99, and ≥ 3.0 mg/L were 1.37 (0.89-2.12) and 2.20 (1.36-3.56), compared with hs-CRP of Conclusion In Korean CKD patients, serum hs-CRP level was low and significantly associated with higher risk of eMACEs and mortality. However, a low serum hs-CRP level was not predictive of adverse kidney outcome, and the predictive performance of hs-CRP was not strong.

Rationale & Objective Studies have suggested associations between lower ratios of serum creatinine to cystatin C with both lower muscle mass and adverse clinical outcomes in multiple disease conditions. Identifying risk factors for mortality among patients with acute kidney injury (AKI) undergoing continuous kidney replacement therapy (CKRT) may improve assessment of prognosis. We sought to evaluate the association of creatinine–cystatin C ratio with outcomes in patients with AKI undergoing CKRT. Study Design Retrospective cohort study. Setting & Participants 1,588 patients treated with intensive care and CKRT for AKI at a tertiary Korean medical center. Predictor Baseline serum creatinine–cystatin C ratio at the time of CKRT initiation. Outcomes Age- and sex-adjusted 90-day mortality after CKRT initiation. Analytical Approach Cox proportional hazard models to estimate the association between creatinine–cystatin C ratio and outcome. Results Mean age was 64.7 ± 14.5 years and 635 patients (40.0%) were women. The range of creatinine–cystatin C ratios was 0.08 to 10.48. The 30- and 90-day mortality rates were significantly lower for the higher creatinine–cystatin C ratio groups. Multivariable Cox proportional hazards regression analyses revealed that mortality risk became successively lower across quartiles of greater creatinine–cystatin C ratio. When creatinine–cystatin C ratio was evaluated using cubic spline analyses, risks for both 30- and 90-day mortality were lower with higher creatinine–cystatin C ratios. These associations remained significant even after adjustment for confounding variables. Limitations Retrospective analysis, serum creatinine and cystatin C may not be in steady state in the setting of AKI. Conclusions Higher serum creatinine–cystatin C ratios were associated with better survival in patients receiving intensive care and CKRT.

While the bone morphogenetic protein‐7 (BMP‐7) is a well‐known therapeutic growth factor reverting many fibrotic diseases, including peritoneal fibrosis by peritoneal dialysis (PD), soluble growth factors are largely limited in clinical applications owing to their short half‐life in clinical settings. Recently, we developed a novel drug delivery model using protein transduction domains (PTD) overcoming limitation of soluble recombinant proteins, including bone morphogenetic protein‐7 (BMP‐7). This study aims at evaluating the therapeutic effects of PTD‐BMP‐7 consisted of PTD and full‐length BMP‐7 on epithelial‐mesenchymal transition (EMT)‐related fibrosis. Human peritoneal mesothelial cells (HPMCs) were then treated with TGF‐β1 or TGF‐β1 + PTD‐BMP‐7. Peritoneal dialysis (PD) catheters were inserted into Sprague‐Dawley rats, and these rats were infused intra‐peritoneally with saline, peritoneal dialysis fluid (PDF) or PDF + PTD‐BMP‐7. In vitro, TGF‐β1 treatment significantly increased fibronectin, type I collagen, α‐SMA and Snail expression, while reducing E‐cadherin expression in HPMCs (P

Optimal blood pressure (BP) control is a major therapeutic strategy in the management of chronic kidney disease (CKD). We studied the association between BP and adverse kidney outcomes within a diverse cohort of Koreans with CKD.Prospective observational cohort study.2,044 participants from the Korean Cohort Study for Outcomes in Patients With CKD (KNOW-CKD).Baseline and time-updated systolic BP (SBP) and diastolic BP (DBP).A composite kidney outcome of a≥50% decline in estimated glomerular filtration rate (eGFR) from the baseline value or incident kidney replacement therapy.Multivariate cause-specific hazards models and marginal structural models were fitted for baseline and time-updated BP, respectively.During 7,472 person-years of follow-up, the primary composite kidney outcome occurred in 473 participants (23.1%), an incidence rate of 63.3 per 1,000 patient-years. Compared with baseline SBP120mm Hg, the hazard ratios (HRs) for 120-129, 130-139, and≥140mm Hg were 1.10 (95% CI, 0.83-1.44), 1.20 (95% CI, 0.93-1.59), and 1.43 (95% CI, 1.07-1.91), respectively. This association was more evident in the model with time-updated SBP, for which the corresponding HRs were 1.31 (95% CI, 0.98-1.75), 1.59 (95% CI, 1.16-2.16), and 2.29 (95% CI, 1.69-3.11), respectively. In the analyses of DBP, we observed that time-updated DBP but not baseline DBP was significantly associated with the composite kidney outcome. Compared to patients with SBP120mm Hg, patients with higher SBP had steeper slopes of eGFR decline. In the model including both SBP and DBP, only SBP was significantly associated with the composite kidney outcome.Observational design, unmeasured confounders, and use of office BPs only.In patients with CKD, higher SBP and DBP levels were associated with a higher risk of a composite kidney outcome reflecting CKD progression. SBP had a greater association with adverse kidney outcomes than DBP.

BackgroundChronic kidney disease (CKD) is a public health problem, and an unfavorable lifestyle has been suggested as a modifiable risk factor for CKD. Cigarette smoking is closely associated with cardiovascular disease and cancers; however, there is a lack of evidence to prove that smoking is harmful for kidney health. Therefore, we aimed to determine the relationship between cigarette smoking and CKD among healthy middle-aged adults.MethodsUsing the database from the Korean Genome and Epidemiology Study, we analyzed 8,661 participants after excluding those with baseline estimated glomerular filtration rate (eGFR)ResultsThe mean age of the subjects was 52 years, and 47.6% of them were males. There were 551 (6.4%) and 1,255 (14.5%) subjects with diabetes and hypertension, respectively. The mean eGFR was 93.0 ml/min/1.73 m2. Among the participants, 5,140 (59.3%), 1,336 (15.4%), and 2,185 (25.2%) were never-smokers, former-smokers, and current-smokers, respectively. During a median follow-up of 11.6 years, incident CKD developed in 1,941 (22.4%) subjects with a crude incidence rate of 25.1 (24.0-26.2) per 1,000 person-years. The multivariable Cox regression analysis after adjustment of confounding factors showed hazard ratios (95% confidence interval) of 1.13 (0.95-1.35) and 1.26 (1.07-1.48) for CKD development in the former- and current-smokers, compared with never-smokers.ConclusionThis study showed that smoking was associated with a higher risk of incident CKD among healthy middle-aged adults.

Objectives: Obesity is a risk factors for chronic kidney disease (CKD). However, the weight changes overtime and this was not well reflected in previous studies. Thus, this study performed to investigated the association body mass index (BMI) trajectories and incident CKD using group-based trajectory modeling. Subjects/Methods: 6,497 healthy subjects without medical comorbidities in the Korean Genome and Epidemiology Study were included in the analysis. Changes in BMI determined by trajectory modeling to accurately identify groups with similar trends of changes in BMI over time; decreasing BMI (slope of BMI per year (%)=-0.481, 95% CI, -0.482 to -0.480), stable BMI (slope=0.001, 95% CI, 0.001-0.002), and increasing BMI (slope=0.499, 95% CI, 0.498-0.501). The primary outcome of interest was incident CKD, which was defined as an estimated glomerular filtration rate of

Background Extracorporeal membrane oxygenation (ECMO) is a cardiorespiratory support technique for patients with circulatory or pulmonary failure. Frequently, large-volume fluid resuscitation is needed to ensure sufficient extracorporeal blood flow in patients initiating ECMO. However, excessive overhydration is known to increase mortality in critically ill patients. Therefore, in order to define a tolerant volume range in patients undergoing ECMO treatment, the association between cumulative fluid balance (CFB) and outcome was evaluated in patients undergoing ECMO. Methods This retrospective multicenter cohort study was conducted with 723 patients who underwent ECMO in three tertiary care hospitals between 2005 and 2016. CFB was calculated as total fluid input minus total fluid output during the first 3 days from ECMO initiation. The patients were divided into groups that initiated ECMO owing to cardiovascular disease (CVD)-related or non-cardiovascular disease (non-CVD)-related causes. The primary endpoint was mortality within 90 days after ECMO commencement. Results Totals of 406 and 317 patients were included in the CVD and non-CVD groups, respectively. In the CVD group, the mean age was 58.4 ± 17.7 years, and 68.2% were male. The mean age was 55.7 ± 15.7 years, and 65.3% were male in the non-CVD group. The median CFB values were 64.7 and 53.5 ml/kg in the CVD and non-CVD groups, respectively. Multivariable analysis using Cox proportional hazards models revealed a significantly increased risk of 90-day mortality in patients with higher CFB values in both the CVD and non-CVD groups. However, the risks were elevated only in the two CFB quartile groups with the largest CFB amounts. Cubic spline models showed that mortality risk began to increase significantly when CFB was 82.3 ml/kg in the CVD group. In patients with respiratory diseases, the mortality risk increase was significant for those with CFB levels above 189.6 ml/kg. Conclusions Mortality risk did not increase until a certain level of fluid overload was reached in patients undergoing ECMO. Adequate fluid resuscitation is critical to improving outcomes in these patients. Electronic supplementary material The online version of this article (10.1186/s13054-018-2211-x) contains supplementary material, which is available to authorized users.

Idiopathic membranous nephropathy (MN) is the most common glomerulonephritis in elderly patients showing nephrotic syndrome. However, little is known about its treatment options and outcomes in elderly MN patients at long term follow-up. We retrospectively enrolled patients with biopsy-proven MN between April 1990 and December 2015 from eight tertiary hospitals in Korea. Among them, we excluded patients who had secondary causes of MN and subnephrotic-range proteinuria. We evaluated the presenting features and clinical outcomes and analyzed the all-cause mortality, renal outcomes, infection, and remission with respect to age. During the median follow-up at 77.2 months, 198 younger patients (

Background Although asymptomatic microscopic hematuria (MH) is a common finding in clinical practice, its long-term outcome remains unknown. Aim This study evaluated the clinical implication of MH in the general population using a large-scale long-term longitudinal cohort database. Methods This study included 8719 participants from the Korean Genome and Epidemiology Study between 2001 and 2014. MH was defined as ≥5 red blood cells per high-power field in random urinalysis without evidence of pyuria. The primary study outcome measure was incident chronic kidney disease (CKD), defined as estimated glomerular filtration rate

Background Adiponectin is an adipokine secreted by adipocytes. A low adiponectin level is a significant risk factor of diabetes mellitus and cardiovascular disease. Recent studies have shown that adiponectin is negatively associated with hematopoiesis and predicts the development of anemia in the general population. In chronic kidney disease (CKD) patients, circulating adiponectin level is paradoxically elevated and the role of adiponectin is complex. Therefore, we evaluated the relationship between adiponectin and anemia in these patients. Methods This prospective longitudinal study included 2113 patients from the KNOW-CKD study (KoreaN cohort study for Outcome in patients With CKD), after excluding 125 without data on adiponectin levels. Hemoglobin levels were measured yearly during a mean follow-up period of 23.7 months. Anemia was defined as hemoglobin levels of Results Mean patient age was 53.6 ± 12.2 years, and 1289 (61%) were men. The mean estimated glomerular filtration rate (eGFR) was 50.4 ± 30.2 mL min−1 1.73 m−2. Serum adiponectin level was inversely associated with body mass index, eGFR, log-transformed C-reactive protein, and positively with Charlson comorbidity index, urine protein to creatinine ratio, and high density lipoprotein cholesterol. In addition, serum adiponectin level was also negatively correlated with hemoglobin level and reticulocyte production index in both men and women. In multivariable linear regression analysis after adjustment of multiple confounders, adiponectin was negatively associated with hemoglobin (men, β = −0.219, P Conclusions A high serum adiponectin level is independently associated with a low hemoglobin level and predicts the development of anemia in patients with CKD. These findings reveal the potential role of adiponectin in CKD-related anemia.

Patients with diabetic nephropathy (DMN) have an increased risk of cardiovascular disease (CVD). However, strategies to reduce this risk are limited. Thyroid hormone replacement therapy (THRT) in patients with hypothyroidism has been shown to reduce several surrogate markers of CVD. Therefore, we performed a study to determine if THRT would reduce CVD risk in patients with subclinical hypothyroidism (SCH) and DMN.This was a retrospective, nonrandomized study of patients with type 2 diabetes, DMN, and SCH. Those with known thyroid dysfunction or taking THRT at baseline were excluded. Patients receiving THRT for at least 180 days were included in the THRT group, while the remaining patients were assigned to the non-THRT group. The primary outcome was CVD events, which included coronary syndrome, cerebrovascular events, and peripheral artery diseases.Among the 257 patients, 83 (32.3%) were in the THRT group. The mean ages were 62.7 ± 12.3 and 66.8 ± 12.4 years in the THRT and non-THRT groups, respectively. The corresponding numbers of male patients were 32 (40.0%) and 94 (53.1%). During a mean follow-up of 38.0 ± 29.2 months, 98 CVD events were observed. Acute coronary syndrome and cerebrovascular event prevalence rates were lower in the THRT group than the non-THRT group, but there was no difference for peripheral artery diseases. Multivariate Cox analysis revealed that THRT was independently associated with a decreased CVD event risk.THRT may decrease the risk of CVD in DMN patients with SCH. Randomized trials are needed to verify this finding.CV = cardiovascular DMN = diabetic nephropathy eGFR = estimated glomerular filtration rate fT4 = free thyroxine HbA1c = glycosylated hemoglobin HR = hazard ratio hs-CRP = high-sensitivity C-reactive protein LDL-C = low-density lipoprotein cholesterol SCH = subclinical hypothyroidism T2DM = type 2 diabetes THRT = thyroid hormone replacement therapy TSH = thyroid-stimulating hormone.