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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.

Background Optimal blood pressure (BP) control is a major therapeutic strategy to reduce adverse cardiovascular events (CVEs) and mortality in patients with chronic kidney disease (CKD). We studied the association of BP with adverse cardiovascular outcome and all-cause death in patients with CKD. Methods Among 2238 participants from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD), 2226 patients with baseline BP measurements were enrolled. The main predictor was systolic BP (SBP) categorized by five levels: Results During the follow-up of 10 233.79 person-years (median 4.60 years), the primary composite outcome occurred in 240 (10.8%) participants, with a corresponding incidence rate of 23.5 [95% confidence interval (CI) 20.7–26.6]/1000 patient-years. MSMs with averaged SBP showed a U-shaped relationship with the primary outcome. Compared with time-updated SBP of 110–119 mmHg, hazard ratios (95% CI) for Conclusions In Korean patients with CKD, there was a U-shaped association of SBP with the risk of adverse clinical outcomes. Our findings highlight the importance of BP control and suggest a potential hazard of SBP

Studies on the mutual relationship between blood pressure (BP) variability and arterial stiffness using time-dependent changes in arterial stiffness are scarce.In this prospective cohort of Korean patients with chronic kidney disease (CKD) G1-G5 without kidney replacement therapy, we studied the bidirectional association between visit-to-visit SBP variability (VVSV) and arterial stiffness in 1036 participants who underwent brachial-ankle pulse wave velocity (baPWV) measurement at baseline and year four. We constructed multivariable logistic regression models using two analytical sets. First, we determined the VVSV [standard deviation (SD)] of all SBP readings over 4 years, and then calculated the odds ratios (ORs) for arterial stiffness progression according to tertiles of VVSV. Arterial stiffness progression was defined as at least 75th percentile of the difference in baPWV between baseline and year four. Second, we analysed the ORs for at least 75th percentile of the 4-year VVSV according to tertiles of baseline baPWV.Compared with the lowest tertile of VVSV (SD), the ORs [95% confidence interval (95% CI)] for arterial stiffness progression were 1.42 (0.96-2.10) and 1.64 (1.11-2.43) for the middle and highest tertiles, respectively. In the second analysis based on tertiles of baseline baPWV, the ORs for at least 75th percentile of VVSV (SD) were 1.41 (95% CI, 0.95-2.10) and 1.64 (95% CI, 1.04-2.61) for the middle and highest tertiles, respectively. This association was similar in both analytical models when VVSV and baPWV were treated as continuous variables.There is a bidirectional relationship between BP variability and arterial stiffness in patients with CKD.

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.

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.

Clinical practice guidelines recommend a target blood pressure (BP)130/80 mm Hg to reduce cardiovascular risk. However, the optimal BP to prevent chronic kidney disease (CKD) is unknown.Population-based retrospective cohort study.10.5 million adults who participated in the National Health Insurance Service National Health Checkup Program in South Korea between 2009 and 2015 and had an estimated glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 mBaseline and time-updated systolic BP (SBP) as a continuous variable and categorized as110, 110 to 119, 120 to 129, 130 to 139, or≥140 mm Hg.Incident CKD GFR categories 3 to 5 (CKD G3-G5), defined as de novo development of estimated GFR60 mL/min/1.73 mCox proportional hazards regression for baseline BP and marginal structural analysis for time-updated BP.During 49,169,311 person-years of follow-up, incident CKD G3-G5 developed in 172,423 (1.64%) individuals with a crude event rate of 3.51 (95% CI, 3.49-3.52) per 1,000 person-years. Compared to a baseline SBP of 120 to 129 mm Hg, HRs for incident CKD G3-G5 for the110, 110 to 119, 130 to 139, and≥140 mm Hg categories were 0.84 (95% CI, 0.82-0.85), 0.92 (95% CI, 0.91-0.94), 1.11 (95% CI, 1.09-1.12), and 1.30 (95% CI, 1.28-1.31), respectively. For time-updated SBPs, corresponding HRs were 0.57 (95% CI, 0.56-0.59), 0.79 (95% CI, 0.78-0.80), 1.58 (95% CI, 1.55-1.60), and 2.49 (95% CI, 2.45-2.53), respectively. Treated as a continuous exposure, each 10-mm Hg higher SBP was associated with 35% higher risk for incident CKD G3-G5 (95% CI, 1.35-1.36).Use of International Classification of Diseases codes to assess comorbid condition burden; residual confounding, and potential selection bias cannot be excluded.In this large national cohort study, higher SBPs were associated with higher risk for incident CKD G3-G5. These findings support evaluation of SBP-lowering strategies to reduce the development of CKD.

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 Although the soluble form of suppression of tumorigenicity 2 (sST2) and soluble low-density lipoprotein receptor relative with 11 ligand-binding repeats (sLR11) have emerged as novel cardiovascular biomarkers in patients with cardiovascular disease, their prognostic value has not been fully investigated in peritoneal dialysis (PD) patients. Methods We included 74 prevalent PD patients from a prospective cohort and measured serum sST2 and sLR11 concentrations by an enzyme-linked immunosorbent assay. The association of these biomarkers and all-cause mortality and major adverse cardiac and cerebrovascular events (MACCEs) was evaluated. Results During a follow-up of 38.5 months, all-cause deaths and MACCEs were observed in 13 (17.6%) patients and 23 (31.3%) patients. Multivariable Cox analyses demonstrated that greater sST2 was independently associated with higher risk of all-cause mortality (≥75.8 ng/mL; hazard ratio [HR] = 5.551; 95% confidence interval [CI] = 1.360–22.660) and MACCEs (≥72.5 ng/mL; HR = 4.609; 95% CI = 1.608–13.208). Furthermore, sST2 showed additive predictive value for mortality to the base model including traditional risk factors (net reclassification index = 0.598, P = 0.04). sLR11 was not significantly associated with all-cause mortality or MACCE. Conclusions sST2, but not sLR11, indicated a significant prognostic value for all-cause mortality and cardiovascular events in PD patients. Further research is needed to validate emerging biomarkers in these populations.

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 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

This study evaluated temporal association of changes in BMI over time with major adverse cardiovascular event (MACE) in Korean middle-aged adults.Between 2001 and 2002, 6855 individuals from the Korean Genome and Epidemiology Study were included and followed up until 2014. The main predictor was the change in BMI determined using group-based trajectory modelling (decreasing, stable, and increasing) from the baseline to 4-, 6-, and 8-years of follow-up. The primary outcome was the occurrence of MACE.During the mean 10.2 years follow-up, MACEs occurred in 350 (5.1 %) individuals. The median (interquartile rage) age of study population was 50 (44-59) years. In primary analysis with 4-year trajectory model, decreasing BMI trajectory was associated with a 1.41-fold higher risk of the MACEs (hazard ratio [HR], 1.41; 95 % confidence interval [CI], 1.06-1.91) compared with stable BMI trajectory. In secondary analyses with 6- and 8-year trajectory models, this association disappeared, and the corresponding HRs (95 % CIs) were 1.14 (0.81-1.61) and 0.98 (0.65-1.49), respectively. There were concomitant improvements in cardiometabolic risk factors in decreasing BMI group, but unfavorable risk burden remained up to 4 to 6 years.The initial 4-year weight loss was paradoxically associated with a higher risk of MACEs, probably due to residual cardiovascular burden. However, this association became null in participants with sustained weight loss ≥ 6 years, suggesting a possible lag effect of weight loss on MACEs.

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.

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 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.

목적: 심방세동과 말기 콩팥병이 동반된 환자에서 항응고제의 치료는 아직 명확히 정립되지 않았다. 본 연구에서는 이러한 환자에서 와파린과 항혈전제의 효과 및 안정성을 비교해 보았다. 방법: 본 연구에서는 2004년 1월부터 2014년 7월까지 단일기관에서 심방세동과 말기 콩팥병을 진단받은 총 256명의 환자 중 와파린(n = 53)이나 항혈전제(n = 105)를 투여받는 CHA2DS2-VASc 점수 1점 이상의 158명(나이, 63.7 ± 12.2세; 남성, n = 103)이 본 연구에 포함되었다. 결과: 총 추적 조사 기간 동안(31.0 ± 29.4개월), 10건의 혈전색전 사건과 29건의 주요 출혈 사건이 발생하였다. 혈전색전 사건의 발생은 와파린군과 항혈전제군 사이에 유의한 차이를 보이지 않았다(1.9%와 8.6%, p = 0.166). 주요 출혈 사건의 발생은 항혈전제군보다 와파린군에서 유의하게 높은 발생률을 보였다(32.1%와 11.4%, p = 0.002). 와파린의 사용은 주요 출혈 사건 발생을 증가시키는 주요한 위험인자였으나(HR, 3.44; 95% CI, 1.60-7.36; p = 0.001) 혈전색전 사건의 발생의 감소와는 통계적으로 유의한 관계를 보이지 않았다(HR, 0.34; 95% CI, 0.04-2.70; p = 0.306). 결론: 심방세동과 말기 콩팥병을 동반한 환자에서 와파린의 사용은 항혈전제와 비교하였을 때 출혈 사건의 위험을 증가시킨다. 결론: 심방세동과 말기 콩팥병을 동반한 환자에서 와파린의 사용은 항혈전제와 비교하였을 때 출혈 사건의 위험을 증가시킨다.

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.

Background The use of newly developed mixed-dilution hemodiafiltration (HDF) can supplement the weaknesses of pre- and postdilution HDF. However, it is unclear whether mixed-HDF performs well compared to predilution HDF. Methods We conducted a prospective, open-labeled, randomized controlled trial from two hemodialysis centers in Korea. Between January 2017 and September 2019, 60 patients who underwent chronic hemodialysis were randomly assigned at a 1:1 ratio to receive either predilution HDF (n = 30) or mixed-HDF (n = 30) for 6 months. We compared convection volume, changes in small- and medium-sized molecule clearance, high-sensitive C-reactive protein (hs-CRP) level, and dialysis-related parameters between the two dialysis modalities. Results A mean effective convection volume of 41.0 ± 10.3 L/session in the predilution HDF group and 51.5 ± 9.0 L/session in the mixed-HDF group was obtained by averaging values of three time-points. The difference in effective convection volume between the groups was 10.5 ± 1.3 L/session. This met the preset noninferiority criteria, suggesting that mixed-HDF was noninferior to predilution HDF. Moreover, the β2-microglobulin reduction rate was greater in the mixed-HDF group than in the predilution HDF group, while mixed-HDF provided greater transmembrane pressure. There were no significant between-group differences in Kt/V urea levels, changes in predialysis hs-CRP levels, proportions of overhydration, or blood pressure values. Symptomatic intradialytic hypotension episodes and other adverse events occurred similarly in the two groups. Conclusion Use of mixed-HDF was comparable to predilution HDF in terms of delivered convection volume and clinical parameters. Moreover, mixed-HDF provided better β2-microglobulin clearance than predilution HDF.

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.

Polypharmacy is a growing and major public health issue, particularly in the geriatric population. This study aimed to examine the association between polypharmacy and the risk of hospitalization and mortality. We included 3,007,620 elderly individuals aged ≥ 65 years who had at least one routinely-prescribed medication but had no prior hospitalization within a year. The primary exposures of interest were number of daily prescribed medications (1–2, 3–4, 5–6, 7–8, 9–10, and ≥ 11) and presence of polypharmacy (≥ 5 prescription drugs per day). The corresponding comparators were the lowest number of medications (1–2) and absence of polypharmacy. The study outcomes were hospitalization and all-cause death. The median age of participants was 72 years and 39.5% were men. Approximately, 46.6% of participants experienced polypharmacy. Over a median follow-up of 5.0 years, 2,028,062 (67.4%) hospitalizations and 459,076 (15.3%) all-cause deaths were observed. An incrementally higher number of daily prescribed medications was found to be associated with increasingly higher risk for hospitalization and mortality. These associations were consistent across subgroups of age, sex, residential area, and comorbidities. Furthermore, polypharmacy was associated with greater risk of hospitalization and death: adjusted HRs (95% CIs) were 1.18 (1.18–1.19) and 1.25 (1.24–1.25) in the overall and 1.16 (1.16–1.17) and 1.25 (1.24–1.25) in the matched cohorts, respectively. Hence, polypharmacy was associated with a higher risk of hospitalization and all-cause death among elderly individuals.

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: Although hypertension is a well known risk factor for CKD, few studies have evaluated the association between temporal trends of systolic BP and kidney function decline in persons without hypertension. METHODS: We studied whether changes in systolic BP over time could influence incident CKD development in 4643 individuals without CKD and hypertension participating in the Korean Genome and Epidemiology Study, a prospective community-based cohort study. Using group-based trajectory modeling, we categorized three distinct systolic BP trajectories: decreasing, stable, and increasing. The primary outcome was incident CKD development, defined as two consecutive eGFR measurements