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Background: In patients undergoing incident hemodialysis, increased fibroblast growth factor-23 (FGF-23) levels are associated with the development of cardiovascular disease (CVD), but the influence of residual kidney function (RFK) on this association is unclear. This study aimed to investigate the association between FGF-23 levels, RKF, and CVD in patients undergoing prevalent hemodialysis., Methods: This cross-sectional and longitudinal observational study included 296 patients undergoing maintenance hemodialysis for at least three months who were followed up for a median of 44 months. RKF was defined as 24-h urine output >200 mL, left ventricular (LV) diastolic dysfunction as E/E' >15 on echocardiographic parameters. CVD was defined as hospitalization or emergency room visits due to cardiovascular causes, such as angina, myocardial infarction, or congestive heart failure., Results: The median intact FGF-23 (iFGF-23) level was 423.8 pg/mL (interquartile range, 171-1,443). Patients with an FGF-23 level > 423.8 pg/mL significantly had a lower proportion of RKF (39.2% vs. 60.1%, P < 0.001) and a higher proportion of LV diastolic dysfunction (54. 1% vs. 29.1%, P < 0.001) than those with an iFGF-23 level ≤ 423.8 pg/mL. The odds ratio (OR) for LV diastolic dysfunction was significantly higher in patients with RFK (OR per one-unit increase in the natural log-transformed iFGF-23 levels, 1.80; 95% confidence interval [CI]: 1.11-2.93) than in patients without RKF (OR per one-unit increase in the natural log-transformed iFGF-23 levels: 1.42; 95% CI: 1.01-1.99) in multivariate analysis (p < 0.001). During the follow-up period, 55 patients experienced CVD. The hazard ratio (HR) for CVD development was also significantly higher in patients with RKF (HR per one-unit increase in the natural log-transformed iFGF-23 levels, 2.64; 95% CI: 1.29-5.40) than those without RKF (HR per one-unit increase in the natural log-transformed iFGF-23 levels: 1.44; 95% CI: 1.04-1.99) in multivariate analysis (p = 0.05)., Conclusions: Increased iFGF-23 levels were associated with LV diastolic dysfunction and CVD development in patients undergoing prevalent hemodialysis; however, the loss of RKF attenuated the magnitude of these associations. Therefore, in these patients, RKF strongly influenced the detrimental role of iFGF-23 in the development of CVD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kee, Jeon, Oh, Cho, Lee, Yoon, Kim, Yoo and Shin.)

Background: This study evaluated temporal association of changes in BMI over time with major adverse cardiovascular event (MACE) in Korean middle-aged adults., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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: <110, 110-119, 120-129, 130-139 and ≥140 mmHg. The primary endpoint was a composite outcome of all-cause death or incident CVEs. We primarily used marginal structural models (MSMs) using averaged and the most recent time-updated SBPs., 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 <110, 120-129, 130-139 and ≥140 mmHg were 2.47 (1.48-4.11), 1.29 (0.80-2.08), 2.15 (1.26-3.69) and 2.19 (1.19-4.01), respectively. MSMs with the most recent SBP also showed similar findings., 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 <110 mmHg., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background Whether visit-to-visit systolic blood pressure (SBP) variability can predict major adverse cardiovascular events (MACE) in patients with chronic kidney disease is unclear. Methods and Results We investigated the relationship between SDs of visit-to-visit SBP variability during the first year of enrollment and MACE among 1575 participants from KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease). Participants were categorized into 3 groups according to tertiles of visit-to-visit SBP variability (SD). The study end point was MACE, defined as a composite of nonfatal myocardial infarction, unstable angina, revascularization, nonfatal stroke, hospitalization for heart failure, or cardiac death. During 6748 patient-years of follow-up (median, 4.2 years), MACE occurred in 64 participants (4.1%). Compared with the lowest tertile of visit-to-visit SBP variability (SD), the hazard ratios (HRs) for the middle and the highest tertile were 1.64 (95% CI, 0.80-3.36) and 2.23 (95% CI, 1.12-4.44), respectively, in a multivariable cause-specific hazard model. In addition, the HR associated with each 5-mm Hg increase in visit-to-visit SBP variability (SD) was 1.21 (95% CI, 1.01-1.45). This association was consistent in sensitivity analyses with 2 additional definitions of SBP variability determined by the coefficient of variation and variation independent of the mean. The corresponding HRs for the middle and highest tertiles were 2.11 (95% CI, 1.03-4.35) and 2.28 (95% CI, 1.12-4.63), respectively, in the analysis with the coefficient of variation and 1.76 (95% CI, 0.87-3.57) and 2.04 (95% CI, 1.03-4.03), respectively, with the variation independent of the mean. Conclusions Higher visit-to-visit SBP variability is associated with an increased risk of MACE in patients with chronic kidney disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.

Objective: Increasing number of clinical guidelines are adopting comprehensive cardiovascular risk assessment tools for treatment decision and disease management. Yet, little is known regarding cardiovascular risks associated with the length of favourable cardiometabolic profile. In this context, we examined whether the duration of strictly ideal cardiovascular health (CVH), based on body mass index, blood pressure, fasting glucose, total cholesterol, cigarette smoking, alcohol drinking and physical activity, in middle age is associated with risk of developing chronic kidney disease (CKD) and cardiovascular disease (CVD) in mid-to-late life., Methods: From the Korean Genome and Epidemiology Study Ansung-Ansan cohort, we included 8020 participants (median age 50.0 years, 47.9% male), of whom, 7854 without CKD and 7796 without CVD at baseline. Cox proportional hazards models were employed to assess CKD and CVD risks, adjusting for age, sex, education level, examination sites and renal markers., Results: Over a median follow-up of 15.0 years, 1401 cases of CKD and 493 cases of CVD were newly developed. Compared with participants with <5 years of ideal CVH duration, HR (95% CI) of those who maintained for 5-<10 years or ≥10 years had negatively graded risks for CKD (5-<10 years, 0.63 (0.39 to 0.93); ≥10 years, 0.33 (0.15 to 0.74)) and CVD (5-<10 years, 0.83 (0.54 to 1.27); ≥10 years, 0.22 (0.08 to 0.60)). In parallel, participants with delayed decline to suboptimal level had lower disease risks compared with counterparts with consistently suboptimal CVH., Conclusion: Our findings confer that maintaining favourable health behaviours and clinical risk factor levels in midlife will improve later-life cardiovascular outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: 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., Methods and Results: 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-C <70 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., Conclusions: 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-C <70 mg/dL, suggesting that a lower LDL-C target may be acceptable., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

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 <40, 50 to 59, and ≥60 mg/dL were 1.10 (0.50-1.82), 0.95 (0.50-1.82), and 0.42 (0.19-0.95), respectively, compared with HDL-C of 40 to 49 mg/dL. However, the significant association for HDL-C ≥60 mg/dL was not seen after Bonferroni correction. In patients with inflammation, we observed a trend toward increased risk of extended major adverse cardiovascular events in higher HDL-C groups (HRs [95% CIs], 0.73 [0.37-1.43], 1.24 [0.59-2.61], and 1.56 [0.71-3.45], respectively), but without statistical significance. 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.

Aims: 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., Methods: 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., Results: 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., Conclusions: In Korean CKD patients, men were more likely to experience adverse cardiovascular events and death than women.

Few studies have investigated the incidence of cardiovascular disease (CVD) in the Asian chronic kidney disease (CKD) population. This study assessed the incidence of CVD, death, and a composite outcome of CVD and death in a prospective Korean predialysis CKD cohort. From a total of 2179 patients, incidence rates were analyzed, and competing risk analyses were conducted according to CKD stage. Additionally, incidence was compared to the general population. During a median 4.1 years of follow-up, the incidence of CVD, all-cause death, and the composite outcome was 17.2, 9.6, and 24.5 per 1000 person-years, respectively. These values were higher in diabetic vs. non-diabetic subjects (P < 0.001). For all outcomes, incidence rates increased with increasing CKD stage (CVD, P = 0.001; death, P < 0.001; and composite, P < 0.001). Additionally, CKD stage G4 [hazard ratio (HR) 2.8, P = 0.008] and G5 (HR 5.0, P < 0.001) were significant risk factors for the composite outcome compared to stage G1 after adjustment. Compared to the general population, the total cohort population (stages G1-G5) showed significantly higher risk of CVD (HR 2.4, P < 0.001) and the composite outcome (HR 1.7, P < 0.001). The results clearly demonstrate that CKD is a risk factor for CVD in an Asian population.

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.

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 <1.0 mg/L. In secondary outcomes, this association was consistent for eMACE and all-cause death; however, hs-CRP was not associated with adverse kidney outcomes. Finally, prediction models failed to show improvement of predictive performance of hs-CRP compared with conventional factors. 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: Association between blood pressure (BP) variability and cardiovascular outcome remains unclear in patients with chronic kidney disease (CKD). We evaluated this association between ambulatory BP variability and cardiovascular events, mortality, and kidney disease progression in patients with CKD., Methods: From the Cardiovascular and Metabolic Disease Etiology Research Center-HIgh Risk study (2013-2018), a total of 470 patients with CKD were analyzed. Ambulatory BP variability was assessed using average real variability (ARV). Primary outcome was composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality. The secondary outcome was rapid kidney function decline [estimated glomerular filtration rate (eGFR), >3 ml/min per 1.73m per year]., Results: During a median follow-up of 51.8 (40.5-56.2) months, the incidences of all-cause death and composite outcomes were higher in the high SBP-ARV group than in the low SBP-ARV group. The Kaplan-Meier analysis showed that a high SBP-ARV, but not a high DBP-ARV and heart rate-ARV, was associated with higher composite outcome risks. In multivariable Cox analysis, a high SBP-ARV correlated with increased composite outcome risks (hazard ratio, 4.53; 95% confidence interval, 1.41-14.58). When subgroup analysis was performed (low vs. high 24-h SBP), this association was only significant in the high 24-h SBP group. The risk stratification for composite outcomes by adding SBP-ARV into the basic model and 24-h SBP, improved by 1.3%. Furthermore, the mean eGFR decline rate was faster, and the rapid eGFR decline risk was 1.68-fold higher in the high SBP-ARV group., Conclusion: Greater ambulatory SBP variabilities were associated with increased risks for nonfatal cardiovascular diseases, all-cause mortality, and rapid kidney function decline in patients with CKD.

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.

The pathogenesis of hypertension is multifactorial in patients with chronic kidney disease (CKD). We explored the relative contribution of arterial stiffness and fluid overload to blood pressure (BP) in these patients. We evaluated 1531 patients from a prospective observational cohort study of high-risk patients with cardiovascular disease. BP, arterial stiffness, and volume status expressed as the extracellular water/total body water ratio (ECW/TBW) were measured by 24-h BP monitoring, pulse-wave velocity (PWV), and bioelectrical impedance analysis, respectively. Multiple linear regression analysis showed that both PWV and ECW/TBW of the patients with CKD were significantly associated with 24-h systolic BP (SBP). The areas under the receiver-operating characteristic curve (AUCs) for predicting 24-h SBP ≥130 mm Hg significantly increased after PWV was added to conventional factors regardless of CKD status. However, the AUCs did not increase in the ECW/TBW-based models. When a cut-off 24-h SBP level of 140 mm Hg was used, the predictability of ECW/TBW for elevated BP significantly improved in patients with CKD (0.718 vs. 0.683, P = 0.034) but not in those without. Notably, a significant impact of arterial stiffness on high BP was consistently observed regardless of CKD status. This association was further confirmed by the net reclassification and integrated discriminant improvements, root mean squared error with adjusted R 2 , and interaction effects. As kidney function declines, fluid overload is significantly associated with high BP. The impact of fluid overload on BP is only observed in more severe hypertension in patients with CKD.

Objective: 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., Methods: 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., Results: 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., Conclusion: THRT may decrease the risk of CVD in DMN patients with SCH. Randomized trials are needed to verify this finding., Abbreviations: 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.

Background: The association of dyslipidemia with mortality has not been fully evaluated in patients on peritoneal dialysis (PD). Moreover, changes in lipids levels over time and associated death risk have not yet been studied in this population., Objective: We studied the association of time-updated serum lipid concentrations with all-cause and cardiovascular (CV) mortalities in a 10-year cohort of 749 incident PD patients., Methods: Association was assessed using time-varying Cox proportional hazard regression models with adjustment for multiple variables including statin therapy., Results: During a median follow-up of 36 (interquartile range, 21-61) months, 273 all-cause and 107 CV deaths occurred. Compared with those with total cholesterol (TC) of 180 to <210 or low-density lipoprotein cholesterol (LDL-C) of 100 to <130 mg/dL, hazard ratios (95% confidence interval) of the lowest TC (<150 mg/dL) and LDL-C (<70 mg/dL) were 2.32 (1.61-3.35) and 2.02 (1.45-2.83) for all-cause mortality and 1.87 (1.04-3.37) and 1.92 (1.13-3.26) for CV mortality, respectively. Lower triglyceride (<100 mg/dL) and high-density lipoprotein cholesterol (<30 mg/dL) levels were associated with higher all-cause mortality (1.66 [1.11-2.47] and 1.57 [1.08-2.29]) but not with CV mortality., Conclusions: Contrary to the general population, lower TC and LDL-C levels over time were significantly associated with both worse survival and increased CV mortality in incident PD patients. Although lower triglyceride and high-density lipoprotein cholesterol concentrations were associated with significantly higher all-cause mortality, they failed to show any clear association with CV mortality. The underlying mechanisms responsible for this apparent paradox await further investigations., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease (CVD) is the most common cause of death in patients with chronic kidney disease (CKD). We report the baseline cardiovascular characteristics of 2,238 participants by using the data of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) study. The cohort comprises 5 subcohorts according to the cause of CKD: glomerulonephritis (GN), diabetic nephropathy (DN), hypertensive nephropathy (HTN), polycystic kidney disease (PKD), and unclassified. The average estimated glomerular filtration rate (eGFR) was 50.5 ± 30.3 mL/min⁻¹/1.73 m⁻² and lowest in the DN subcohort. The overall prevalence of previous CVD was 14.4% in all patients, and was highest in the DN followed by that in the HTN subcohort. The DN subcohort had more adverse cardiovascular risk profiles (higher systolic blood pressure [SBP], and higher levels of cardiac troponin T, left ventricular mass index [LVMI], coronary calcium score, and brachial-ankle pulse wave velocity [baPWV]) than the other subcohorts. The HTN subcohort exhibited less severe cardiovascular risk profiles than the DN subcohort, but had more severe cardiovascular risk features than the GN and PKD subcohorts. All these cardiovascular risk profiles were inversely correlated with eGFR. In conclusion, this study shows that the KNOW-CKD cohort exhibits high cardiovascular burden, as other CKD cohorts in previous studies. Among the subcohorts, the DN subcohort had the highest risk for CVD. The ongoing long-term follow-up study up to 10 years will further delineate cardiovascular characteristics and outcomes of each subcohort exposed to different risk profiles., Competing Interests: The authors have no potential conflicts of interest to disclose.

Recent reports demonstrated that dentin matrix protein 1 (DMP1) acts as an inhibitor of vascular calcification and might be a potential biomarker for chronic kidney disease-mineral and bone disorder; however, no clinical investigations regarding DMP1 have been performed in dialysis patients. We investigated the prognostic value of DMP1 on cardiovascular outcomes in prevalent peritoneal dialysis patients. We recruited 223 prevalent peritoneal dialysis patients and divided them into high and low DMP1 groups according to log-transformed plasma DMP1 levels. Lateral lumbar spine radiographs were used for measurement of vascular calcification. Major cardiovascular events were compared between the two groups. A Cox proportional hazards analysis determined DMP1 was independently associated with cardiovascular outcomes. In vitro mouse osteocytes were cultured in media containing indoxyl sulfate (IS), and the expressions of DMP1 were examined. The mean age was 52.1 ± 11.8 years, and 116 (52.0%) patients were male. The median value of log DMP1 was 0.91 (0.32-2.81 ng/mL). The multiple logistic regression analysis indicated that DMP1 levels were independently associated with the presence of vascular calcification after adjustment for multiple confounding factors (odds ratio = 0.719; 95% confidence interval [CI] 0.522-0.989; p = 0.043). During a mean follow-up duration of 34.6 months, incident cardiovascular events were observed in 41 (18.4%) patients. A Kaplan-Meier plot showed that the low DMP1 group had a significantly higher rate of incident cardiovascular events compared with the high DMP1 group (log-rank test, p = 0.026). In addition, multiple Cox analysis showed that low DMP1 was significantly associated with incident cardiovascular events (log 1 increase: hazard ratio = 0.855; 95% CI 0.743-0.984; p = 0.029) after adjustment for multiple confounding factors. In IS-stimulated osteocytes, mRNA and protein expression levels of DMP1 were significantly decreased compared with control osteocytes. We showed that low DMP1 levels were significantly associated with presence of vascular calcification and were independently associated with the incident cardiovascular events in prevalent peritoneal dialysis patients. DMP1 might be a potential factor contributing to cardiovascular complications in dialysis patients. © 2016 American Society for Bone and Mineral Research., (© 2016 American Society for Bone and Mineral Research.)

Unlabelled: Abnormal bone dynamics is a major risk factor for cardiovascular disease in patients with chronic kidney disease. The level of serum intact parathyroid hormone (iPTH) is widely used as a bone dynamic marker. We investigated the effect of the mean level of serum iPTH on overall mortality and cardiovascular outcomes in incident dialysis patients., Purpose: Chronic kidney disease-mineral bone disorder (CKD-MBD) is a major risk factor for cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). CKD-MBD is classified as low- or high-turnover bone disease according to the bone dynamics; both are related to vascular calcification in ESRD. To evaluate the prognostic value of abnormal serum parathyroid hormone (PTH) levels on ESRD patients, we investigated the effects of time-averaged serum intact PTH (TA-iPTH) levels on overall mortality and major adverse cardiac and cerebrovascular events (MACCEs) in incident dialysis patients., Methods: Four hundred thirteen patients who started dialysis between January 2009 and September 2013 at Yonsei University Health System were enrolled. The patients were divided into three groups according to TA-iPTH levels during the 12 months after the initiation of dialysis: group 1, <65 pg/ml; group 2, 65-300 pg/ml; and group 3, >300 pg/ml. Cox regression analyses were performed to determine the prognostic value of TA-iPTH for overall mortality and MACCEs., Results: The mean age of the patients was 57 ± 15 years, and 222 patients (54 %) were men. During the median follow-up of 40.8 ± 29.3 months, 49 patients (12 %) died, and MACCEs occurred in 55 patients (13 %). The multivariate Cox regression analyses demonstrated that a low TA-iPTH level was an independent risk factor for both overall mortality (group 2 as reference; group 1: hazard ratio (HR) = 2.06, 95 % confidence interval (CI) = 1.11-3.83, P = 0.023) and MACCEs (HR = 1.82, 95 % CI = 1.04-3.20, P = 0.036) in incident dialysis patients after adjustment for confounding factors., Conclusion: Low serum TA-iPTH is a useful clinical marker of both overall mortality and MACCEs in patients undergoing incident dialysis, mediated by vascular calcification.

Diabetic kidney disease leads to microalbuminuria and gradually progresses to overt proteinuria with renal insufficiency. Recent studies have demonstrated that 20% to 40% of patients with diabetic kidney disease are normo- to microalbuminuric, despite reduced renal function. We investigated renal and cardiovascular outcomes in patients with diabetes and renal insufficiency who were normo-, micro-, and macroalbuminuric. Patients with diabetes and stage III or IV chronic kidney disease were recruited and divided into normoalbuminuric, microalbuminuric, and macroalbuminuric groups. New-onset cardiovascular events and renal outcomes, defined by end-stage renal disease or a 50% decline in estimated glomerular filtration rate, were evaluated. Among the 1136 study patients, 255 (22.4%) were normoalbuminuric. During a mean follow-up duration of 44 months, the incidence of cardiovascular disease was similar among groups (P = 0.68). However, renal outcomes were significantly more common in patients with macroalbuminuria than in those who were normoalbuminuric or microalbuminuric (P < 0.001). Multivariate Cox analysis identified macroalbuminuria and estimated glomerular filtration rate as independent predictors of renal outcomes. The amount of albuminuria was not associated with cardiovascular events in this population. Although cardiovascular events were similar in patients with diabetic kidney disease and renal insufficiency, renal outcomes differed significantly according to the amount of albuminuria.

Background: Dialysis patients are at high risk for cardiovascular diseases, but until now there have been no detailed analyses of the incidences among Asian patients initiating dialysis. The aims of this study were to determine the incidence rates of major adverse cardiac and cerebrovascular events (MACCE) and to compare them between incident HD patients and PD patients., Methods: We included all patients who had started dialysis between January 1, 2005 and December 31, 2008 in Korea, and analyzed 30,279 eligible patients [22,892 hemodialysis (HD) patients and 7387 peritoneal dialysis (PD) patients] by intention-to-treat. Median follow-up was 21.5 months., Results: The crude incidence rates were as follows: MACCE, 182 per 1000 patient-years (PY); major adverse cardiac events (MACE), 138/1000 PY; all-cause mortality, 116/1000 PY; non-fatal acute myocardial infarction (AMI), 18/1000 PY; target vessel revascularization (TVR), 17/1000 PY; and non-fatal stroke, 60/1000 PY. When comparing all baseline covariate-adjusted relative risks between HD and PD patients, HD is overall superior to PD in terms of MACCE. Further examined by each endpoint, all-cause mortality, non-fatal AMI, and TVR occurred significantly more frequently in patients on PD than in those on HD, whereas non-fatal hemorrhagic stroke occurred significantly more frequently in patients on HD than in those on PD., Conclusions: The incidence of MACCE may be different from Western dialysis patients. HD is overall superior to PD in terms of MACCE as an initial dialysis modality. Underlying mechanisms differentially affecting cardiovascular outcomes by dialysis modality remain to be further elucidated., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background and Aim: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients on peritoneal dialysis (PD). Hyponatremia was recently shown to be a modifiable factor that is strongly associated with increased mortality in PD patients. However, the clinical impact of hyponatremia on CV outcomes in these patients is unclear., Methods: To determine whether a low serum sodium level predicts the development of CV disease, we carried out a prospective observational study of 441 incident patients who started PD between January 2000 and December 2005. Time-averaged serum sodium (TA-Na) levels were determined to investigate the ability of hyponatremia to predict newly developed CV events in these patients., Results: During a mean follow-up of 43.2 months, 106 (24.0%) patients developed new CV events. The cumulative incidence of new-onset CV events after the initiation of PD was significantly higher in patients with TA-Na levels ≤ 138 mEq/L than in those with a TA-Na > 138 mEq/L. After adjustment for multiple potentially confounding covariates, an increase in TA-Na level was found to be associated with a significantly lower risk of CV events (subdistribution hazard ratio per 1 mEq/L increase, 0.90; 95% confidence interval, 0.83-0.96; p = 0.003). Patients with a TA-Na ≤ 138 mEq/L had a 2.31-fold higher risk of suffering a CV event., Conclusions: These results provide evidence of a clear association between low serum sodium and new-onset CV events after dialysis initiation in PD patients. Whether the correction of hyponatremia for this indication provides additional protection for the development of CV disease in these patients remains to be addressed in interventional studies.

Background: Diastolic heart failure (HF), the prevalence of which is gradually increasing, is associated with cardiovascular (CV) morbidity and mortality in the general population and, more specifically, in patients with end-stage renal disease (ESRD). However, the impact of diastolic dysfunction on CV outcomes has not been studied in incident dialysis patients with preserved systolic function., Methods: This prospective observational cohort study investigates the clinical consequence of diastolic dysfunction and the predictive power of diastolic echocardiographic parameters for CV events in 194 incident ESRD patients with normal or near normal systolic function, who started dialysis between July 2008 and August 2012., Results: During a mean follow-up duration of 27.2 months, 57 patients (29.4%) experienced CV events. Compared to the CV event-free group, patients with CV events had a significantly higher left ventricular (LV) mass index, ratio of early mitral flow velocity (E) to early mitral annulus velocity (E') (E/E'), LA volume index (LAVI), deceleration time, and right ventricular systolic pressure, and a significantly lower LV ejection fraction and E'. In multivariate Cox proportional hazard analysis, E/E'>15 and LAVI>32 mL/m2 significantly predicted CV events (E/E'>15: hazard ratio [HR] = 5.40, 95% confidence interval [CI] = 2.73-10.70, P< .001; LAVI>32 mL/m2: HR = 5.56, 95% CI = 2.28-13.59, P< .001]. Kaplan-Meier analysis revealed that patients with both E/E'>15 and LAVI>32 mL/m2 had the worst CV outcomes., Conclusion: An increase in E/E' or LAVI is a significant risk factor for CV events in incident dialysis patients with preserved LV systolic function.

Residual renal function (RRF) is associated with left ventricular (LV) hypertrophy as well as all-cause and cardiovascular (CV) mortality in patients with end-stage renal disease. However, no studies have yet examined the serial changes in echocardiographic findings according to the rate of RRF decline in incident dialysis patients. A total of 81 patients who started peritoneal dialysis (PD) between 2005 and 2012 at Yonsei University Health System, Seoul, South Korea, and who underwent baseline and follow-up echocardiography within the first year of PD were recruited. Patients were dichotomized into "faster" and "slower" RRF decline groups according to the median values of RRF decline slope (-1.60 mL/min/y/1.73 m(2)). Baseline RRF and echocardiographic parameters were comparable between the 2 groups. During the first year of PD, there were no significant changes in LV end-diastolic volume index (LVEDVI), left atrial volume index (LAVI), or LV mass index (LVMI) in the "faster" RRT decline group, while these indices decreased in the "slower" RRT decline group. The rate of RRF decline was a significant determinant of 1-year changes in LVEDVI, LAVI, and LVMI. The linear mixed model further confirmed that there were significant differences in the changes in LVEDVI, LAVI, and LVMI between the 2 groups (P = 0.047, 0.048, and 0.001, respectively). During a mean follow-up duration of 31.9 months, 4 (4.9%) patients died. Compared with the "slower" RRF decline group, CV composite (20.29/100 vs 7.18/100 patient-years [PY], P = 0.098), technique failure (18.80/100 vs 4.19/100 PY, P = 0.006), and PD peritonitis (15.73/100 vs 4.95/100 PY, P = 0.064) developed more frequently in patients with "faster" RRF decline rate. On multivariate Cox regression analysis, patients with "faster" RRF decline rate showed 4.82-, 4.44-, and 7.37-fold higher risks, respectively, for each clinical outcome. Preservation of RRF is important for conserving cardiac performance, resulting in an improvement in clinical outcomes of incident PD patients.

Background: The impact of serum ferritin on prognosis in patients starting hemodialysis (HD) is not fully elucidated., Methods: A prospective cohort of 946 incident HD patients from 26 dialysis centers in Korea was selected for this study. Patients were divided into tertiles according to natural logarithm (Ln) ferritin concentrations., Results: During a median follow-up of 39 months, 88 (9.3%) patients died. Multivariate Cox proportional hazard analysis demonstrated that Ln ferritin was independently associated with an increase in cardiovascular mortality risk (hazard ratio (HR) 1.604, 95% CI 1.040-2.474, p = 0.033), infection-related mortality risk (HR 1.916, 95% CI 1.056-3.476, p = 0.032), and all-cause mortality risk (HR 1.547, 95% CI 1.156-2.069, p = 0.003)., Conclusion: Serum ferritin levels at the time of HD commencement were a significant independent risk factor for mortality regardless of systemic inflammation and nutritional status. Therefore, elevated serum ferritin levels could be an effective indicator for prognosis., (© 2015 S. Karger AG, Basel.)

Numerous studies have demonstrated that cardiac biomarkers are significant predictors of cardiovascular (CV) and all-cause mortality in ESRD patients, but most of the studies were retrospective or included small numbers of patients, only prevalent dialysis patients, or measured 1 or 2 biomarkers. This study was to analyze the association between 3 cardiac biomarkers and mortality in incident HD patients. A prospective cohort of 864 incident HD patients was followed for 30 months. Based on the median values of baseline NT-proBNP, cTnT, and hsCRP, the patients were divided into "high" and "low" groups, and CV and all-cause mortality were compared between each group. Additionally, time-dependent ROC curves were constructed, and the NRI and IDI of the models with various biomarkers were calculated. The CV survival rates were significantly lower in the "high" NT-proBNP and cTnT groups compared to the corresponding "low" groups, while there was no significant difference in CV survival rate between the 2 hsCRP groups. However, all-cause mortality rates were significantly higher in all 3 "high" groups compared to each lower group. In multivariate analyses, only Ln NT-proBNP was found to be an independent predictor of mortality. Moreover, NT-proBNP was a more prognostic marker for mortality compared to cTnT. In conclusion, NT-proBNP is the biomarker that results in the most added prognostic value on top of traditional risk factors for CV and all-cause mortality in incident HD patients.

Endothelial dysfunction is implicated in increased cardiovascular risk in nondialyzed population. However, the prognostic impact of endothelial dysfunction on cardiovascular outcome has not been investigated in peritoneal dialysis (PD) patients. We prospectively determined endothelial function by brachial artery endothelium-dependent vasodilation (flow-mediated dilation [FMD]) in 143 nondiabetic PD patients and 32 controls. Primary outcome was a major adverse cardiac and cerebrovascular event (MACCE). Brachial FMD was significantly lower in PD patients than in controls (2.9% [1.3-4.7] vs 6.2% [5.4-8.3], P < 0.001). During a mean follow-up of 42 months, primary outcome was observed in 25 patients (17.5%). When patients were dichotomized by the median value of FMD (2.9%), incidence rates of MACCEs were significantly higher in the group with lower FMD compared with higher FMD (7.2 vs 3.0/100 person-years, P = 0.03). In multivariate Cox analysis, low FMD (≤2.9%) was a significant independent predictor of MACCEs (hazard ratio = 2.73, 95% confidence interval = 1.03-7.22, P = 0.04). Furthermore, multivariate fractional polynomial analysis showed that the risk of MACCE decreased steadily with higher FMD values. Impaired brachial FMD was a significant independent predictor of MACCEs in PD patients. Estimating endothelial dysfunction by brachial FMD could be useful for stratifying cardiovascular risk in these patients.

Background: The progression and complications of chronic kidney disease should differ depending on the cause (C), glomerular filtration rate category (G), and albuminuria (A). The KNOW-CKD (KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease), which is a prospective cohort study, enrolls subjects with chronic kidney disease stages 1 to 5 (predialysis)., Methods/design: Nine nephrology centers in major university hospitals throughout Korea will enroll approximately 2,450 adults with chronic kidney disease over a 5-year period from 2011 to 2015. The participating individuals will be monitored for approximately 10 years until death or until end-stage renal disease occurs. The subjects will be classified into subgroups based on the following specific causes of chronic kidney disease: glomerulonephritis, diabetic nephropathy, hypertensive nephropathy, polycystic kidney disease, and others. The eligible subjects will be evaluated at baseline for socio-demographic information, detailed personal/family history, office BP, quality of life, and health behaviors. After enrollment in the study, thorough assessments, including laboratory tests, cardiac evaluation and radiologic imaging, will be performed according to the standardized protocol. The biospecimen samples will be collected regularly. A renal event is defined by >50% decrease in estimated GFR (eGFR) from the baseline values, doubling of serum creatinine, or end-stage renal disease. The primary composite outcome consists of renal events, cardiovascular events, and death. As of September 2013, 1,470 adult chronic kidney disease subjects were enrolled in the study, including 543 subjects with glomerulonephritis, 317 with diabetic nephropathy, 294 with hypertensive nephropathy and 249 with polycystic kidney disease., Discussion: As the first large-scale chronic kidney disease cohort study to be established and maintained longitudinally for up to 10 years, the KNOW-CKD will help to clarify the natural course, complication profiles, and risk factors of Asian populations with chronic kidney disease., Trial Registration: No. NCT01630486 at http://www.clinicaltrials.gov.

Background: The aim of this study was to investigate the association between the dialysate MCP-1 (dMCP-1) and systemic inflammatory and nutritional markers in peritoneal dialysis (PD) patients. In addition, we examined the prognostic value of dMCP-1 on all-cause or cardiovascular mortality in these patients., Methods: We prospectively followed 169 prevalent PD patients from April 1st 2008 to December 31st 2012. At baseline, dMCP-1 and serum biochemical parameters including high sensitivity CRP (hs-CRP) and albumin were checked. All-cause mortality and cause of death were evaluated during the follow-up period. Based on the median level of dMCP-1, patients were classified as either low or high dMCP-1 groups., Results: Mean age, hs-CRP, and D/Pcr ratio at 4 h were significantly higher, while serum albumin levels and %lean body mass (LBM) were significantly lower in the high dMCP-1 group. During the mean follow-up period of 47.7 months, all-cause mortality and cardiovascular mortality rate were significantly higher in the high dMCP-1 group (9.6 and 6.3 per 100 person-years, respectively) compared to the low dMCP-1 group (5.1 and 3.1 per 100 person-years, respectively; p = 0.021, 0.038). In multivariate Cox analysis, high dMCP-1 was a significant independent predictor of all-cause mortality (hazard ratio: 1.83, 95% confidence interval: 1.03-3.24, p = 0.039)., Conclusions: dMCP-1 levels are closely correlated with nutritional and systemic inflammatory markers in PD patients. In addition, increased dMCP-1 is significantly associated with higher all-cause and cardiovascular mortality. These findings suggest that local peritoneal inflammation could contribute to poor clinical outcomes in PD patients., (© 2014 S. Karger AG, Basel.)

Background/aims: Using a cohort of incident hemodialysis (HD) patients, this study investigated the impact of lipid profiles on clinical outcomes, especially in the early period of dialysis., Methods: A prospective cohort of 867 incident HD patients was selected. In order to determine the impact of cholesterol level on primary outcome, Cox regression analyses were performed for LDL and non-HDL (NHDL) variables., Results: Univariate analysis revealed an increase in primary outcome risk with an LDL cholesterol level of 100 mg/dl or higher compared to an LDL cholesterol level lower than 100 mg/dl. High LDL cholesterol remained a significant independent predictor of the composite outcome, even after adjusting for age, gender, diabetes mellitus, preexisting CV disease, albumin, and hs-CRP., Conclusion: Serum LDL cholesterol at the time of HD commencement was a significant independent risk factor for the composite outcome of all-cause mortality and CV events in incident HD patients during the early stages of dialysis., (© 2014 S. Karger AG, Basel.)

Background: Interdialytic weight gain (IDWG) has been regarded as a surrogate of volume overload, but also as a marker of a better nutritional status in end-stage renal disease (ESRD) patients on hemodialysis (HD). This paradoxical meaning of IDWG requires further investigation, particularly in adverse cardiovascular outcomes., Methods: A prospective cohort of 1,013 incident HD patients from 36 HD centers of the Clinical Research Center for ESRD in Korea was included. Patients were categorized into five groups according to the IDWG%, a ratio of absolute IDWG to dry weight: <1.0, ≥4.0, and every 1.0 increment in between. Primary outcome was major adverse cardiac and cerebrovascular events (MACCE)., Results: During a mean follow-up of 18.7 months, primary outcome was observed in 104 patients (10.3%). In multivariate analysis, compared to patients with IDWG% of 1.0-1.9 (reference group), the hazard ratios (HRs) for primary outcome in the IDWG% <1.0, 2.0-2.9, 3.0-3.9, and ≥4.0 groups were 1.10 [95% confidence interval (CI) 0.55-2.20, p = 0.80], 1.15 (95% CI 0.59-2.27, p = 0.68), 1.80 (95% CI 0.95-3.41, p = 0.07), and 1.93 (95% CI 1.02-3.64, p = 0.04), respectively. Furthermore, even when residual renal function and 24-hour urine volume were adjusted, IDWG% ≥4.0 remained as a significant predictor of primary outcome (HR 2.03, 95% CI 1.02-4.02, p = 0.04)., Conclusion: Increased IDWG% is a significant independent predictor of MACCE in incident HD patients. It could be helpful to prevent excessive IDWG for improving clinical outcomes in incident HD patients.

Backgrounds and Aims: Visceral fat has a crucial role in the development and progression of cardiovascular disease, the major cause of death in end-stage renal disease (ESRD). Although sagittal abdominal diameter (SAD), as an index of visceral fat, significantly correlated with mortality in the general population, the impact of SAD on clinical outcomes has never been explored in ESRD patients. Therefore, we sought to elucidate the prognostic value of SAD in incident peritoneal dialysis (PD) patients., Methods: We prospectively determined SAD by lateral abdominal X-ray at PD initiation, and evaluated the association of SAD with all-cause and cardiovascular mortality in 418 incident PD patients., Results: The mean SAD was 24.5 ± 4.3 cm, and during a mean follow-up of 39.4 months, 97 patients (23.2%) died, and 49.4% of them died due to cardiovascular disease. SAD was a significant independent predictor of all-cause [3rd versus 1st tertile, HR (hazard ratio): 3.333, 95% CI (confidence interval): 1.514-7.388, P = 0.01; per 1 cm increase, HR: 1.071, 95% CI: 1.005-1.141, P = 0.03] and cardiovascular mortality (3rd versus 1st tertile, HR: 8.021, 95% CI: 1.994-32.273, P = 0.01; per 1 cm increase, HR: 1.106, 95% CI: 1.007-1.214, P = 0.03). Multivariate fractional polynomial analysis also showed that all-cause and cardiovascular mortality risk increased steadily with higher SAD values. In addition, SAD provided higher predictive value for all-cause (AUC: 0.691 vs. 0.547, P<0.001) and cardiovascular mortality (AUC: 0.644 vs. 0.483, P<0.001) than body mass index (BMI). Subgroup analysis revealed higher SAD (≥ 24.2 cm) was significantly associated with all-cause mortality in men, women, younger patients (<65 years), and patients with lower BMI (<22.3 kg/m(2))., Conclusions: SAD determined by lateral abdominal X-ray at PD initiation was a significant independent predictor of all-cause and cardiovascular mortality in incident PD patients. Estimating visceral fat by SAD could be useful to stratify mortality risk in these patients.

Backgrounds: Osteoprotegerin (OPG) is known to regulate bone mineral metabolism and to be also associated with inflammation, cardiovascular disease (CVD) and mortality. Malnutrition-inflammation-atherosclerosis (MIA) syndrome is commonly found and closely linked to mortality in dialysis patients. The aim of this study was to investigate the associations between OPG and MIA syndrome in prevalent peritoneal dialysis (PD) patients., Methods: Prevalent PD patients for more than 6 months were prospectively followed up from March 2005 to May 2010. At baseline, OPG, hs-CRP, albumin, and %lean body mass (LBM) by creatinine kinetics were checked, and subjective global assessment (SGA) was performed. New-onset cardiovascular events were evaluated during the study period. Based on the median level of OPG, patients were classified as lower OPG (LO) group (n = 88) and higher OPG (HO) group (n = 88)., Results: A total of 176 patients (age 52.0 ± 11.8 years, male 50.6%, duration of PD 105.3 ± 67.2 months) were recruited and followed. In HO group, age, hs-CRP level and Charlson's comorbidity indices were higher, whereas serum albumin level, %LBM and SGA score were significantly lower than LO group. OPG levels were positively correlated with inflammatory markers, whereas negatively correlated with nutritional status. Cardiovascular events occurred in 51 patients during the study period. Newly developed cardiovascular events were significantly common in HO group (n = 36, 40.9%) than LO group (n = 15, 17%, p = 0.002). Cox regression analysis revealed that higher OPG level (per 1-SD increase in OPG, HR: 1.44; 95% CI: 1.03-2.00; p = 0.034) was a significant risk factor for cardiovascular events even after adjustments for demographic and biochemical parameters., Conclusion: OPG was significantly correlated with markers of systemic inflammation and malnutrition and was a significant predictor of CVD in PD patients. These findings suggest OPG might be a prognostic indicator of MIA syndrome in prevalent PD patients., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Recent studies revealed that elevated cardiac troponin T (cTnT) could predict all-cause mortality and cardiovascular diseases in end-stage renal disease patients. This study aimed to evaluate cTnT as a prognostic value in asymptomatic continuous ambulatory peritoneal dialysis patients., Methods: This is a prospective observational study with 107 prevalent peritoneal dialysis patients. cTnT, high-sensitive C-reactive protein (hsCRP) and IL-6 were measured at baseline. Based on cTnT level, patients were classified as higher cTnT group (HT, n = 21, cTnT > or =0.1 ng/ml) and lower cTnT group (LT, n = 86, cTnT <0.1 ng/ml), and were followed for 3 years. Primary endpoint was cardiovascular events., Results: The HT group had a significantly higher level of log hsCRP and log IL-6 than the LT group (p < 0.05). Kaplan-Meier survival demonstrated worse cardiovascular event-free survival for the HT group. Multivariate analysis adjusted for age, cTnT, IL-6 and hsCRP level revealed that age (per 1-year increase, HR 1.07, p < 0.05), elevated cTnT (vs. <0.1 ng/ml, HR 5.89, p < 0.05) and hsCRP (vs. <3.0 mg/l, HR 4.15, p < 0.05) were identified as significant determinants of cardiovascular events., Conclusion: This study suggests that cTnT may be an aid in risk stratification of continuous ambulatory peritoneal dialysis patients., (Copyright (c) 2008 S. Karger AG, Basel.)

Objective: Increasing number of clinical guidelines are adopting comprehensive cardiovascular risk assessment tools for treatment decision and disease management. Yet, little is known regarding cardiovascular risks associated with the length of favourable cardiometabolic profile. In this context, we examined whether the duration of strictly ideal cardiovascular health (CVH), based on body mass index, blood pressure, fasting glucose, total cholesterol, cigarette smoking, alcohol drinking and physical activity, in middle age is associated with risk of developing chronic kidney disease (CKD) and cardiovascular disease (CVD) in mid-to-late life.Methods: From the Korean Genome and Epidemiology Study Ansung-Ansan cohort, we included 8020 participants (median age 50.0 years, 47.9% male), of whom, 7854 without CKD and 7796 without CVD at baseline. Cox proportional hazards models were employed to assess CKD and CVD risks, adjusting for age, sex, education level, examination sites and renal markers.Results: Over a median follow-up of 15.0 years, 1401 cases of CKD and 493 cases of CVD were newly developed. Compared with participants with <5 years of ideal CVH duration, HR (95% CI) of those who maintained for 5-<10 years or ≥10 years had negatively graded risks for CKD (5-<10 years, 0.63 (0.39 to 0.93); ≥10 years, 0.33 (0.15 to 0.74)) and CVD (5-<10 years, 0.83 (0.54 to 1.27); ≥10 years, 0.22 (0.08 to 0.60)). In parallel, participants with delayed decline to suboptimal level had lower disease risks compared with counterparts with consistently suboptimal CVH.Conclusion: Our findings confer that maintaining favourable health behaviours and clinical risk factor levels in midlife will improve later-life cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Background. A potential independent association was recently demonstrated between high red blood cell distribution width (RDW) and the risk of all-cause mortality in patients with cardiovascular disease, although the mechanism remains unclear. However, there have been no reports on the relationship between RDW and mortality in acute kidney injury (AKI) patients treated with continuous renal replacement therapy (CRRT). In this study, we assessed whether RDW was associated with mortality in AKI patients on CRRT treatment in the intensive care unit (ICU). Methods. We enrolled 470 patients with AKI who were treated with CRRT at the Yonsei University Medical Center ICU from August 2007 to September 2009 in this study. We performed a retrospective analysis of demographic, biochemical parameters and patient outcomes. Following CRRT treatment, 28-day all-cause mortality was evaluated. Results. At the initiation of CRRT treatment, RDW level was significantly correlated with white blood cell count, hemoglobin (Hb) and total cholesterol. Patients with high RDW levels exhibited significantly higher 28-day mortality rates than patients with low RDW levels (P < 0.01). Baseline RDW level, Sequential Organ Failure Assessment (SOFA) score, low mean arterial pressure (MAP) and low cholesterol levels were independent risk factors for mortality. In multivariate Cox proportional hazard analyses, RDW at CRRT initiation was an independent predictor for 28-day all-cause mortality after adjusting for age, gender, MAP, Hb, albumin, total cholesterol, C-reactive protein and SOFA score. Conclusion. Our study demonstrates that RDW could be an additive predictor for all-cause mortality in AKI patients on CRRT treatment in the ICU. [ABSTRACT FROM AUTHOR]

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

Background: Klotho, a protein linked to aging, has emerged as a pivotal player in mineral bone metabolism and might explain the relationship between chronic kidney disease (CKD) and cardiovascular disease (CVD). The present study aimed to investigate the association between serum klotho and cardiac parameters from a large-scale Korean CKD cohort.Methods: We analyzed 2101 participants from KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort who had been measured for serum klotho levels. Left ventricular hypertrophy evaluated by left ventricular mass index (LVMI) and arterial stiffness measured by brachial-to-ankle pulse wave velocity (baPWV) were explored as cardiovascular parameters.Results: Patients were 53.6 ± 12.2 years old and 61.1% were male. The mean estimated glomerular filtration rate (eGFR) was 53.0 ± 30.7 mL/min/1.73m2. The median serum klotho level was 536 (interquartile range [IQR]: 420-667) pg/mL. Advanced CKD stages were associated with lower serum klotho levels (P < 0.001, P for linear trend < 0.001). Ascending quartiles of klotho were significantly associated with decreased LMVI (P < 0.001, P for linear trend< 0.001). A multivariable linear regression model showed serum klotho had a significant inverse association with LVMI (β - 0.04; 95% CI [confidence interval] -0.004, - 0.00007; P = 0.041). However, there was no significant association between serum klotho and baPWV after adjustment (β 0.003; 95% CI -0.04, 0.05; P = 0.876).Trial Registration: This trial was registered on ClinicalTrials.gov on 28 June 2012 ( NCT01630486 ).Conclusions: Serum klotho was an independent biomarker of LVMI, but not arterial stiffness. [ABSTRACT FROM AUTHOR]

Background: Association between high body mass index (BMI) and survival benefit is confounded by comorbid conditions such as nutritional status and inflammation. Patients with acute kidney injury (AKI), particularly those receiving continuous renal replacement therapy (CRRT), are highly catabolic and more susceptible to loss of energy. Herein, we evaluated whether disease severity can modify the relationship between BMI and mortality.Methods: We conducted an observational study in 1144 patients who had undergone CRRT owing to various causes of AKI between 2010 and 2014. Patients were categorized into four groups; underweight (< 18.5 kg/m2), normal (18.5-22.99 kg/m2), overweight (23.0-24.99 kg/m2), and obesity (≥25 kg/m2) according to BMI classification by the Committee of Clinical Practice Guidelines and Korean Society for the Study of Obesity. More severe disease was defined as sepsis-related organ failure assessment (SOFA) score of ≥ a median value of 12. The study endpoint was death that occurred within 30 days after the initiation of CRRT.Results: The mean age was 63.2 years and 439 (38.4%) were females. The median BMI was 23.6 (20.9-26.2) kg/m2. The obese group were younger and higher SOFA score than normal BMI group. In a multivariable Cox regression analysis, we found a significant interaction between BMI and SOFA score (P <  0.001). Furthermore, obese patients were significantly associated with a lower risk of death as compared to normal BMI group after adjusting confounding factors [hazard ratio (HR), 0.81; 95% confidence interval (CI), 0.68-0.97; P = 0.03]. This association was only evident among patients with high severity (HR, 0.61; 95% CI, 0.48-0.76, P <  0.001). In contrast, in those with low severity, survival benefit of high BMI was lost, whereas underweight was associated with an increased risk of death (HR, 1.74; 95% CI, 1.16-2.60; P = 0.007).Conclusion: In this study, we found a survival benefit of high BMI in AKI patients undergoing CRRT, particularly in those with more disease severity; the effect was not observed in those with less disease severity. [ABSTRACT FROM AUTHOR]