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.

Previous studies have reported the relationship between thyroid hormone levels and mortality in dialysis patients. However, little is known about the association of free thyroxine (fT4) and mortality in patients on peritoneal dialysis (PD). This study investigated the association between basal and annual variation in fT4 level and mortality in PD patients.

Although numerous previous studies have explored various biomarkers for their ability to predict mortality in end-stage renal disease (ESRD) patients, these studies have been limited by retrospective analyses, mostly prevalent dialysis patients, and the measurement of only 1 or 2 biomarkers. This prospective study was aimed to evaluate the association between 3 biomarkers and mortality in incident 335 ESRD patients starting continuous ambulatory peritoneal dialysis (CAPD) in Korea. According to the baseline NT-proBNP, cTnT, and hsCRP levels, the patients were stratified into tertiles, and cardiovascular (CV) and all-cause mortalities were compared. Additionally, time-dependent ROC curves were constructed, and the net reclassification index (NRI) and integrated discrimination improvement (IDI) of the models with various biomarkers were calculated. We found the upper tertile of NT-proBNP was significantly associated with increased risk of both CV and all-cause mortalities. However, the upper tertile of hsCRP was significantly related only to the high risk of all-cause mortality even after adjustment for age, sex, and white blood cell counts. Moreover, NT-proBNP had the highest predictive power for CV mortality, whereas hsCRP was the best prognostic marker for all-cause mortality among these biomarkers. In conclusions, NT-proBNP is a more significant prognostic factor for CV mortality than cTnT and hsCRP, whereas hsCRP is a more significant predictor than NT-proBNP and cTnT for all-cause mortality in incident peritoneal dialysis patients.

Mesangial C3 deposition is frequently observed in patients with IgA nephropathy (IgAN). However, the role of complement in the pathogenesis or progression of IgAN is uncertain. In this observational cohort study, we aimed to identify the clinical implications of circulating C3 levels and mesangial C3 deposition and to investigate their utility as predictors of renal outcomes in patients with IgAN.

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 < 0.05) and two (sexual function and dialysis staff encouragement, all P < 0.05) ESRD domains were still higher in patients on PD compared with patients on HD at one and two years after initiation of dialysis, respectively. PD shows better HRQOL during the initial period after dialysis even after adjusting for clinical and socioeconomic characteristics, and the effect lasts up to two years. It was similar in terms of changes in HRQOL over time between HD and PD.

Chronic kidney disease (CKD) is a public health problem, and an unfavorable lifestyle has been suggested as a modifiable risk factor for CKD. Cigarette smoking is closely associated with cardiovascular disease and cancers; however, there is a lack of evidence to prove that smoking is harmful for kidney health. Therefore, we aimed to determine the relationship between cigarette smoking and CKD among healthy middle-aged adults.

Herein, we aim to assess mortality risk prediction in peritoneal dialysis patients using machine-learning algorithms for proper prognosis prediction. A total of 1,730 peritoneal dialysis patients in the CRC for ESRD prospective cohort from 2008 to 2014 were enrolled in this study. Classification algorithms were used for prediction of N-year mortality including neural network. The survival hazard ratio was presented by machine-learning algorithms using survival statistics and was compared to conventional algorithms. A survival-tree algorithm presented the most accurate prediction model and outperformed a conventional method such as Cox regression (concordance index 0.769 vs 0.745). Among various survival decision-tree models, the modified Charlson Comorbidity index (mCCI) was selected as the best predictor of mortality. If peritoneal dialysis patients with high mCCI (>4) were aged ≥70.5 years old, the survival hazard ratio was predicted as 4.61 compared to the overall study population. Among the various algorithm using longitudinal data, the AUC value of logistic regression was augmented at 0.804. In addition, the deep neural network significantly improved performance to 0.841. We propose machine learning-based final model, mCCI and age were interrelated as notable risk factors for mortality in Korean peritoneal dialysis patients.

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.

Extracellular fluid (ECF) excess is an independent predictor of cardiovascular morbidity in patients undergoing dialysis. This study aimed to investigate the relationship between ECF status, which is affected by renal function, and coronary artery calcification (CAC), which is a marker of cardiovascular disease, in patients with chronic kidney disease (CKD).

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.

While the bone morphogenetic protein-7 (BMP-7) is a well-known therapeutic growth factor reverting many fibrotic diseases, including peritoneal fibrosis by peritoneal dialysis (PD), soluble growth factors are largely limited in clinical applications owing to their short half-life in clinical settings. Recently, we developed a novel drug delivery model using protein transduction domains (PTD) overcoming limitation of soluble recombinant proteins, including bone morphogenetic protein-7 (BMP-7). This study aims at evaluating the therapeutic effects of PTD-BMP-7 consisted of PTD and full-length BMP-7 on epithelial-mesenchymal transition (EMT)-related fibrosis. Human peritoneal mesothelial cells (HPMCs) were then treated with TGF-β1 or TGF-β1 + PTD-BMP-7. Peritoneal dialysis (PD) catheters were inserted into Sprague-Dawley rats, and these rats were infused intra-peritoneally with saline, peritoneal dialysis fluid (PDF) or PDF + PTD-BMP-7. In vitro, TGF-β1 treatment significantly increased fibronectin, type I collagen, α-SMA and Snail expression, while reducing E-cadherin expression in HPMCs (P < .001). PTD-BMP-7 treatment ameliorated TGF-β1-induced fibronectin, type I collagen, α-SMA and Snail expression, and restored E-cadherin expression in HPMCs (P < .001). In vivo, the expressions of EMT-related molecules and the thickness of the sub-mesothelial layer were significantly increased in the peritoneum of rats treated with PDF, and these changes were significantly abrogated by the intra-peritoneal administration of PTD-BMP-7. PTD-BMP-7 treatment significantly inhibited the progression of established PD fibrosis. These findings suggest that PTD-BMP-7, as a prodrug of BMP-7, can be an effective therapeutic agent for peritoneal fibrosis in PD patients.

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).

Objective: Dementia is prevalent among elderly patients undergoing hemodialysis. However, the association between dialysis adequacy and the risk of dementia is uncertain. Methods: A total of 10,567 patients aged >65 years undergoing maintenance hemodialysis who participated in a national hemodialysis quality assessment program were analyzed. The patients were classified into quartile groups based on single-pool Kt/V levels. The associations between single-pool Kt/V and the development of dementia, Alzheimer's disease (AD), and vascular dementia (VD) were examined. Results: The mean age of the patients was 72.9 years, and 43.4% were female. The mean baseline single-pool Kt/V level was 1.6 ± 0.3. During a median follow-up of 45.6 (45.6-69.9) months, there were 27.6, 23.9, and 2.8 events/1,000 person-years of overall dementia, AD, and VD, respectively. The incidences of overall dementia, AD, and VD were lowest in the highest single-pool Kt/V quartile group. Compared with the lowest single-pool Kt/V quartile, the risks of incident overall dementia and AD were significantly lower in the highest quartile [sub-distribution hazard ratio (sHR): 0.69, 95% confidence interval (CI): 0.58-0.82 for overall dementia; sHR: 0.69, 95% CI: 0.57-0.84 for AD]. Inverse relationships were found between the risks of developing overall dementia and AD, and single-pool Kt/V. However, no significant relationship was observed between single-pool Kt/V levels and VD development. Conclusions: Increased dialysis clearance was associated with a lower risk of developing dementia in elderly hemodialysis patients.

The NLRP3 inflammasome is activated by mitochondrial damage and contributes to kidney fibrosis. However, it is unknown whether PGC-1α, a key mitochondrial biogenesis regulator, modulates NLRP3 inflammasome in kidney injury. Primary renal tubular epithelial cells (RTECs) were isolated from C57BL/6 mice. The NLRP3 inflammasome, mitochondrial dynamics and morphology, oxidative stress, and cell injury markers were examined in RTECs treated by TGF-β1 with or without Ppargc1a plasmid, PGC-1α activator (metformin), and siPGC-1α. In vivo, adenine-fed and unilateral ureteral obstruction (UUO) mice were treated with metformin. In vitro, TGF-β1 treatment to RTECs suppressed the expressions of PGC-1α and mitochondrial dynamic-related genes. The NLRP3 inflammasome was also activated and the expression of fibrotic and cell injury markers was increased. PGC-1α induction with the plasmid and metformin improved mitochondrial dynamics and morphology and attenuated the NLRP3 inflammasome and cell injury. The opposite changes were observed by siPGC-1α. The oxidative stress levels, which are inducers of the NLRP3 inflammasome, were increased and the expression of TNFAIP3, a negative regulator of NLRP3 inflammasome regulated by PGC-1α, was decreased by TGF-β1 and siPGC-1α. However, PGC-1α restoration reversed these alterations. In vivo, adenine-fed and UUO mice models showed suppression of PGC-1α and TNFAIP3 and dysregulated mitochondrial dynamics. Moreover, the activation of oxidative stress and NLRP3 inflammasome, and kidney fibrosis were increased in these mice. However, these changes were significantly reversed by metformin. This study demonstrated that kidney injury was ameliorated by PGC-1α-induced inactivation of the NLRP3 inflammasome via modulation of mitochondrial viability and dynamics.

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.

Statin use in end-stage kidney disease (ESKD) patients are not encouraged due to low cardioprotective effects. Although the risk of hepatocellular carcinoma (HCC), a frequently occurring cancer in East Asia, is elevated in ESKD patients, the relationship between statins and HCC is not known despite its possible chemopreventive effect. The relationship between statin use and HCC development in ESKD patients with chronic hepatitis was evaluated. In total, 6165 dialysis patients with chronic hepatitis B or C were selected from a national health insurance database. Patients prescribed with ≥ 28 cumulative defined daily doses of statins during the first 3 months after dialysis commencement were defined as statin users, while those not prescribed with statins were considered as non-users. Primary outcome was the first diagnosis of HCC. Sub-distribution hazard model with inverse probability of treatment weighting was used to estimate HCC risk considering death as competing risk. During a median follow-up of 2.8 years, HCC occurred in 114 (3.2%) statin non-users and 33 (1.2%) statin users. The HCC risk was 41% lower in statin users than in non-users (sub-distribution hazard ratio, 0.59; 95% confidence interval [CI], 0.42-0.81). The weighted incidence rate of HCC was lower in statin users than in statin non-users (incidence rate difference, - 3.7; 95% CI - 5.7 to - 1.7; P < 0.001). Incidence rate ratio (IRR) was also consistent with other analyses (IRR, 0.56; 95% CI, 0.41 to 0.78; P < 0.001). Statin use was associated with a lower risk of incident HCC in dialysis patients with chronic hepatitis B or C infection.

The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations without a race coefficient have gained recognition across the United States. We aimed to test whether these new equations performed well in Korean patients with chronic kidney disease (CKD).

Guidelines for general hypertension treatment do not recommend the combined use of renin-angiotensin-aldosterone system (RAAS) inhibitors due to the risk of hyperkalemia. However, a recent clinical trial showed that polycystic kidney disease (PKD) patients had infrequent episodes of hyperkalemia despite receiving combined RAAS inhibitors. Because intrarenal RAAS is a main component for renal potassium handling, we further investigated the association between intrarenal RAAS activity and serum potassium level in patients with chronic kidney disease, particularly in PKD patients, and examined whether intrarenal RAAS activity has a prognostic role in patients with PKD.

Conflicting results still exist regarding the benefit of renin-angiotensin-aldosterone system (RAAS) blockade on clinical outcomes in dialysis patients. The aim of this study was to evaluate the effects of RAAS blockade on survival in Korean patients with end-stage renal disease (ESRD).

Although numerous studies have tried to elucidate the best dialysis modality in end-stage renal disease patients with diabetes, results were inconsistent and varied with the baseline characteristics of patients. Furthermore, none of the previous studies on diabetic dialysis patients accounted for the impact of glycemic control. We explored whether glycemic control had modifying effect on mortality between hemodialysis (HD) and peritoneal dialysis (PD) in incident dialysis patients with diabetes. A total of 902 diabetic patients who started dialysis between August 2008 and December 2013 were included from a nationwide prospective cohort in Korea. Based on the interaction analysis between hemoglobin A1c (HbA1c) and dialysis modalities for patient survival (P for interaction = 0.004), subjects were stratified into good and poor glycemic control groups (HbA1c< or ≥8.0%). Differences in survival rates according to dialysis modalities were ascertained in each glycemic control group after propensity score matching. During a median follow-up duration of 28 months, the relative risk of death was significantly lower in PD compared with HD in the whole cohort and unmatched patients (whole cohort, hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.47-0.90, P = 0.01; patients with available HbA1c [n = 773], HR = 0.64, 95% CI = 0.46-0.91, P = 0.01). In the good glycemic control group, there was a significant survival advantage of PD (HbA1c <8.0%, HR = 0.59, 95% CI = 0.37-0.94, P = 0.03). However, there was no significant difference in survival rates between PD and HD in the poor glycemic control group (HbA1c ≥8.0%, HR = 1.21, 95% CI = 0.46-2.76, P = 0.80). This study demonstrated that the degree of glycemic control modified the mortality risk between dialysis modalities, suggesting that glycemic control might partly contribute to better survival of PD in incident dialysis patients with diabetes.