Early fluid management affects short-term mortality in patients with end-stage kidney disease undergoing chronic hemodialysis and requiring continuous renal replacement therapy.

BACKGROUND: Early fluid management is considered a key element affecting mortality in critically ill patients requiring continuous renal replacement therapy (CRRT). Most studies have primarily focused on patients with intrinsic acute kidney injury requiring CRRT, although end-stage kidney disease (ESKD) patients generally exhibit greater vulnerability. We investigated the association between fluid balance and short-term mortality outcomes in ESKD patients undergoing chronic hemodialysis and requiring CRRT. METHODS: This retrospective study included 110 chronic hemodialysis patients who received CRRT between 2017 and 2019 at Ewha Womans University Mokdong Hospital. The amounts of daily input and output, and cumulative 3-day and 7-day input and output, were assessed from the initiation of CRRT. The participants were classified into two groups based on 7-day and 14-day mortalities. Cox regression analyses were carried out on the basis of the amounts of daily input and output, cumulative input and output, and cumulative fluid balance. RESULTS: During follow-up, 7-day and 14-day mortalities were observed in 24 (21.8%) and 34 (30.9%) patients. The patients were stratified into two groups (14-day survivors vs. non-survivors), and there were no significant differences in demographic characteristics between the two groups. However, diabetes mellitus was more common among survivors than among non-survivors. Univariate analyses showed that the amounts of daily output at 48, and 72 h, and 3-day cumulative input and output, were significantly associated with 7-day mortality risk regardless of the cumulative fluid balance (HR: 0.28, 95% CI: 0.12-0.70, p = 0.01 for daily output at 48 h; HR: 0.34, 95% CI: 0.13-0.85, p = 0.02 for daily output at 72 h.; HR: 0.72, 95% CI: 0.61-0.86, p = 0.01 for 3-day cumulative input; HR: 0.65, 95% CI: 0.41-0.90, p = 0.01 for 3-day cumulative output). Adjusted multivariate analyses showed that the lower 3-day cumulative output is an independent risk factor for 7-day and 14-day mortality. CONCLUSIONS: In our study, increased cumulative output were significantly associated with reduced short-term mortality risk in chronic hemodialysis patients undergoing CRRT regardless of cumulative fluid balance. Further prospective studies to investigate the association between fluid balance and mortality in ESRD patients requiring CRRT are warranted.

The effect of uric acid and urinary sodium excretion on prehypertension: a nationwide population-based study.

BACKGROUND: This study examined the effect of serum uric acid (SUA) level and urinary sodium excretion on blood pressure as well as their combined effect on prehypertension in a Korean population. METHOD: Data from the 7th Korea National Health and Nutrition Examination Survey for adults (≥ 19 years of age) were used. The participants were classified into two groups, normotension and prehypertension, according to the JNC-7 definition. Logistic regression was carried out and adjusted for traditionally regarded confounders of blood pressure. All analyses considered a complex sampling design. A multivariate analysis was performed on subgroups defined according to their SUA level and urinary sodium excretion. RESULTS: The 4200 participants were divided into normotension (n = 2646) and prehypertension (n = 1554) groups. In the univariate analysis, patient age, male sex, concurrent comorbidity (diabetes mellitus, cardiovascular disease, stroke, dyslipidemia, and chronic kidney disease), uric acid, and urinary sodium excretion were associated with prehypertension. After adjusting for baseline covariates, both the SUA level and urinary sodium excretion were significant predictors of incident prehypertension (SUA, per 1 mg/dL increase, odds ratio [OR] 1.216, 95% confidence interval [95% CI] 1.131-1.309; urinary sodium excretion, per 1 g/day increase, OR 1.067, 95% CI 1.019-1.117). Additionally, simultaneously higher tertiles of SUA and urinary sodium excretion resulted in higher ORs for prehypertension. CONCLUSION: Increased SUA is a significant risk marker for the development of prehypertension in normotensives. Simultaneously high SUA and urinary sodium excretion amplified the effect on the development of prehypertension. Our findings suggest that lowering SUA levels and reducing sodium intake will contribute to preventing hypertension.

The interactive effects of input and output on managing fluid balance in patients with acute kidney injury requiring continuous renal replacement therapy.

BACKGROUND: The interactive effect of cumulative input and output on achieving optimal fluid balance has not been well elucidated in patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). This study evaluated the interrelation of fluid components with mortality in patients with AKI requiring CRRT. METHODS: This is a retrospective observational study conducted with a total of 258 patients who were treated with CRRT due to AKI between 2016 and 2018 in the intensive care unit of Ewha Womans University Mokdong Hospital. The amounts of fluid input and output were assessed at 24-h and 72-h from the initiation of CRRT. The study endpoints were 7- and 28-day all-cause mortality. RESULTS: The mean patient age was 64.7 ± 15.8 years, and 165 (64.0%) patients were male. During the follow-up, 7- and 28-day mortalities were observed in 120 (46.5%) and 157 (60.9%) cases. The patients were stratified into two groups (28-day survivors vs. non-survivors), and the cumulative fluid balances (CFBs) at 24 h and 72 h were significantly higher in the 28-day non-survivors compared with the survivors. The increase in 24-h and 72-h CFB was significantly associated with an increase in 7- and 28-day mortality risks. To examine the interactive effect of cumulative input or output on the impact of CFB on mortality, we also stratified patients into three groups based on the tertile of 24-h and 72-h cumulative input or output. The increases in 24-h and 72-h CFBs were still significantly related to the increases in 7-day and 28-day mortality, irrespective of the cumulative input. However, we did not find significant associations between increase in 24-h and 72-h CFB and increase in mortality risk in the groups according to cumulative output tertile. CONCLUSIONS: The impact of cumulative fluid balance on mortality might be more dependent on cumulative output. The physicians need to decrease the cumulative fluid balance of CRRT patients as much as possible and consider increasing patient removal.

Dementia is a risk factor for major adverse cardiac and cerebrovascular events in elderly Korean patients initiating hemodialysis: a Korean national population-based study.

BACKGROUND: Dementia is common in end-stage renal disease (ESRD) patients on hemodialysis (HD) and is associated with worse outcomes. This study aimed to investigate the risk of major adverse cardiac and cerebrovascular event (MACCE) in elderly patients with dementia initiating HD. METHODS: Using the database from the Health Insurance Review & Assessment Service, we analyzed 10,171 patients aged 65 years or older who had initiated dialysis from 2005 to 2008. MACCE was defined as a composite outcome of all-cause mortality, nonfatal acute myocardial infarction, target vessel revascularization, and nonfatal ischemic and hemorrhagic stroke. The Kaplan-Meier method and Cox proportional hazards model were used, and further comparisons using propensity-score matching at 1:2 ratio were also performed. RESULTS: A total of 303 elderly patients (3.0%) had dementia at initiating HD. During follow-up, dementia was a significant predictor of MACCE after adjustment for confounding variables. In addition, further analyzed in the propensity-score matched groups, dementia was an independent predictor of both nonfatal ischemic stroke and all-cause mortality. CONCLUSIONS: Dementia is an independent risk factor for mortality and ischemic stroke in elderly ESRD patients initiating HD. Patients with dementia who start dialysis should be closely monitored to reduce the risk of mortality and ischemic stroke.

A population-based approach indicates an overall higher patient mortality with peritoneal dialysis compared to hemodialysis in Korea.

To date, only a few large-scale studies have measured the effect of dialysis modality on mortality in Asian populations. Here, we sought to compare survival between incident hemodialysis (HD) and peritoneal dialysis (PD) patients using the Korean Health Insurance Review & Assessment Service database. This enabled us to perform a population-based complete survey that included 32,280 incident dialysis patients and followed them for a median of 26.5 months. To reduce biases due to nonrandomization, we first matched 7049 patient pairs with similar propensity scores. Using the log-rank test, we found the mortality rate in PD patients was significantly higher than that in HD patients. Subsequent subgroup analyses indicated that in older patients (55 years and older), with the exception of the subgroup of patients with no comorbidities and the subgroup of patients with malignancy, PD was consistently associated with a higher mortality rate. In younger patients (under 55 years), regardless of the covariates, the survival rate of PD patients was comparable to that of HD patients. Thus, while the overall mortality rate was higher in incident PD patients, mortality rates of some incident PD and HD patients were comparable in Korea.

Non-dipper status and left ventricular hypertrophy as predictors of incident chronic kidney disease.

We have hypothesized that non-dipper status and left ventricular hypertrophy (LVH) are associated with the development of chronic kidney disease (CKD) in non-diabetic hypertensive patients. This study included 102 patients with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m(2). Ambulatory blood pressure monitoring and echocardiography were performed at the beginning of the study, and the serum creatinine levels were followed. During the average follow-up period of 51 months, CKD developed in 11 patients. There was a significant difference in the incidence of CKD between dippers and non-dippers (5.0% vs 19.0%, P < 0.05). Compared to patients without CKD, patients with incident CKD had a higher urine albumin/creatinine ratio (52.3 ± 58.6 mg/g vs 17.8 ± 29.3 mg/g, P < 0.01), non-dipper status (72.7% vs 37.4%, P < 0.05), the presence of LVH (27.3% vs 5.5%, P < 0.05), and a lower serum HDL-cholesterol level (41.7 ± 8.3 mg/dL vs 50.4 ± 12.4 mg/dL, P < 0.05). Based on multivariate Cox regression analysis, non-dipper status and the presence of LVH were independent predictors of incident CKD. These findings suggest that non-dipper status and LVH may be the therapeutic targets for preventing the development of CKD in non-diabetic hypertensive patients.

Clinical implication of metabolic syndrome on chronic kidney disease depends on gender and menopausal status: results from the Korean National Health and Nutrition Examination Survey.

BACKGROUND: The prevalence of chronic kidney disease (CKD) has been increasing throughout the world over the last decade. Metabolic syndrome (MS) has been known to be an independent risk factor of CKD. However, both renal and metabolic diseases are experienced differently in men and women, and clinical implication of MS on CKD may be different according to gender. METHODS: To understand the association between MS and CKD, we performed a cross-sectional study in non-institutionalized civilians using the data of the Korean National Health and Nutrition Examination Survey. Of 37 769 participants, 5091 were available for the analysis of the prevalence of CKD (defined as dipstick proteinuria or a reduced GFR < 60 ml/min/1.73 m(2)). RESULTS: The prevalence of CKD was 8.9% (7.4% in men, 4.7% in premenopausal women and 20.1% in postmenopausal women) and MS was seen in 26.2% (24.9% in men, 13.9% in premenopausal women and 52% in postmenopausal women). The prevalence of CKD increased with ageing, in particular after sharply after the age of 50 in both genders. MS was a significant determinant of CKD; however, sub-analysis revealed that MS was a risk factor for CKD only in men under the age of 60 and in postmenopausal women. Neither MS per se nor individual components of MS were associated with CKD in men over the age of 60 and in premenopausal women. CONCLUSION: Differential effect of MS on CKD according to age and gender in our study may provide a clue to define the subject in need for more attention for the treatment of MS in terms of the development of CKD.

A case report of crescentic glomerulonephritis associated with Hantaan virus infection.

Although various glomerular diseases in hantavirus infection have been reported, an association between hantavirus infection and crescentic glomerulonephritis has not been described. Herein, we report a case of immune complex-mediated crescentic glomerulonephritis in a 70-year-old man with Hantaan virus infection.

Factors Associated with Early Mortality in Critically Ill Patients Following the Initiation of Continuous Renal Replacement Therapy.

Continuous renal replacement therapy (CRRT) is an important modality to support critically ill patients, and the need for CRRT treatment has been increasing. However, CRRT management is costly, and the associated resources are limited. Thus, it remains challenging to identify patients that are likely to have a poor outcome, despite active treatment with CRRT. We sought to elucidate the factors associated with early mortality after CRRT initiation. We analyzed 240 patients who initiated CRRT at an academic medical center between September 2016 and January 2018. We compared baseline characteristics between patients who died within seven days of initiating CRRT (early mortality), and those that survived more than seven days beyond the initiation of CRRT. Of the patients assessed, 130 (54.2%) died within seven days of CRRT initiation. Multivariate logistic regression models revealed that low mean arterial pressure, low arterial pH, and high Sequential Organ Failure Assessment score before CRRT initiation were significantly associated with increased early mortality in patients requiring CRRT. In conclusion, the mortality within seven days following CRRT initiation was very high in this study. We identified several factors that are associated with early mortality in patients undergoing CRRT, which may be useful in predicting early outcomes, despite active treatment with CRRT.

Gender-specific discrepancy in subjective global assessment for mortality in hemodialysis patients.

Although subjective global assessment (SGA) is a widely used representative tool for nutritional investigations even among dialysis patients, no studies have examined gender-specific differences in the ability of SGA to predict mortality in hemodialysis (HD) patients. A total of 2,798 dialysis patients were enrolled from clinical research center for end-stage renal disease (CRC for ESRD) between 2009 and 2015. The cohort was divided into two groups based on nutritional status as evaluated by SGA: 'good nutrition' and 'mild to severe malnutrition'. Multivariate Cox proportional regression analyses were performed to investigate gender-specific differences in SGA for mortality among incident and prevalent HD patients. 'Mild to severe malnutrition' was significantly correlated with increased mortality compared with 'good nutrition' for all HD, incident and prevalent HD patients. Compared with 'good nutrition', 'mild to severe malnutrition' was also more significantly associated with increased mortality in male patients in the incident and prevalent HD groups. However, no significant associations between nutritional status evaluated by SGA and mortality were observed for female patients. SGA of HD patients can be useful for predicting mortality, especially in male HD patients. However, SGA alone might not reflect adverse outcomes in female patients.

Association of blood pressure components with mortality and cardiovascular events in prehypertensive individuals: a nationwide population-based cohort study.

BACKGROUND: The effects of each blood pressure index [systolic and diastolic blood pressure (SBP, DBP), pulse pressure (PP), mean arterial pressure (MAP)] on the occurrence of mortality and cardiovascular (CV) events have not yet been investigated in prehypertensive populations. METHODS: A total of 30,258 prehypertensive Korean participants underwent periodic health examination between 2003 and 2004 were enrolled, and the associations of BP components with mortality and CV events were investigated. Moreover, based on the DBP [80 ≤ DBP <90 mmHg (N = 21,323) and DBP <80 mmHg (N = 8,935)], the effects of BP components were also evaluated. RESULTS: Multivariate Cox analyses in prehypertensive group revealed that the hazard ratios (HRs) were 1.121 and 1.130 per 10 mmHg increase in SBP and PP for mortality, respectively. Additionally, 10 mmHg increase of SBP (HR:1.090) was still significantly, but increase of PP (HR:1.060) was marginally associated with higher incidence of CV events. However, there were no significant associations with increase in DBP or MAP on adverse clinical outcomes in prehypertensive group. In the prehypertensive subjects with DBP <80 mmHg, CV events more frequently occurred by 38.8% and 28.5% per 10 mmHg increase in SBP and PP, respectively. CONCLUSIONS: Prehypertensive subjects might need to be cautioned when they have high SBP or PP with low DBP even in healthy populations. Key message Prehypertensive subjects should be cautioned when they have high-systolic blood pressure or pulse pressure with low-diastolic blood pressure, even without previous hypertension, diabetes mellitus or chronic kidney disease.

The additional benefit of weighted subjective global assessment (SGA) for the predictability of mortality in incident peritoneal dialysis patients: A prospective study.

Although subjective global assessment (SGA) is a widely used tool for nutritional investigation, the scores are dependent on the inspectors' subjective opinions, and there are only few studies that directly assessed the usefulness of SGA and modified SGA in incident peritoneal dialysis (PD) patients. A total of 365 incident PD patients between 2009 and 2015 were enrolled and measured with SGA and calculated using serum albumin and total iron binding capacity (TIBC) levels for weighted SGA. Cox analyses were performed to delineate the association between SGA or weighted SGA and all-cause mortality, and a receiver-operating characteristic was conducted to reveal the additional benefit of weighted SGA on predicting adverse clinical outcomes. The Kaplan-Meier curve showed that the cumulative survival rate in patients with "Good nutrition" (G1) was significantly higher compared to those with "Mild to severe malnutrition" (G2). G2 was significantly associated with an increase in the mortality even after adjusting for several covariates compared with G1. Moreover, a 1-unit increase in weighted SGA was also significantly correlated with mortality after adjustment of the same covariates, while G2 was not significantly associated with an increase in the mortality among young-aged (under 65 years) groups. Meanwhile, a 1-unit increase in weighted SGA was significantly related to an increase in mortality in all the subgroup analyses. Furthermore, the AUCs of weighted SGAs in all groups were significantly increased compared with those of SGA alone. In conclusions, the evaluation of nutritional status based on SGA in incident PD patients might be useful for predicting mortality. However, weighted SGA with serum albumin and TIBC can provide additional predictive power for mortality compared with SGA alone in incident PD patients.

Blood Pressure Control During Chronic Kidney Disease Progression.

BACKGROUND: Hypertension is a major cause of end-stage renal disease, and blood pressure (BP) control is crucial in patients with chronic kidney disease (CKD). However, it is generally inadequately controlled in CKD patients. We investigated the prevalence of CKD patients with inadequate BP control and its related factors, based on the CKD stage. METHODS: We analyzed the health examination sample cohort database, which consisted of the randomly selected participants among all the citizens who received the health examination provided by National Health Insurance Service of Korea in 2012 and 2013. RESULTS: There were 27,350 CKD patients (7.9%) out of a total of 345,044 participants. As CKD stage progressed, there were more patients with poorly controlled hypertension compared to those with well-controlled hypertension. In addition, systolic BP increased with CKD stage progression, while diastolic BP was not significantly different. Age, female, body mass index, increased pulse pressure, CKD stage, and levels of fasting glucose, total cholesterol, hemoglobin, and proteinuria were significant factors associated with poor control of BP in hypertensive CKD patients. CONCLUSION: The proportion of CKD patients with poorly controlled hypertension significantly increased as CKD progressed, mainly associated with the increase in pulse pressure. However, future investigation for causal relationship between poorly controlled hypertension and its related factors is needed.

Middle East respiratory syndrome clinical practice guideline for hemodialysis facilities.

The Korean Society of Nephrology participated in the task force team consisting of government authorities and civilian experts to prevent and control the spread of Middle East respiratory syndrome (MERS) in 2015. The Korean Society of Nephrology MERS Task Force Team took an immediate action and drafted 'the clinical recommendation for hemodialysis facilities' to follow when the first and the only confirmed case was reported in the hemodialysis unit. Owing to the dedicated support from medical doctors, dialysis nurses, and related medical companies, we could prevent further transmission of MERS infection successfully in hemodialysis units. This special report describes the experience of infection control during MERS outbreak in 2015 and summarizes the contents of 'the clinical practice guideline for hemodialysis facilities dealing with MERS patients' built upon our previous experience.

Selective tubular activation of hypoxia-inducible factor-2α has dual effects on renal fibrosis.

Hypoxia-inducible factor (HIF) is a key transcriptional factor in the response to hypoxia. Although the effect of HIF activation in chronic kidney disease (CKD) has been widely evaluated, the results have been inconsistent until now. This study aimed to investigate the effects of HIF-2α activation on renal fibrosis according to the activation timing in inducible tubule-specific transgenic mice with non-diabetic CKD. HIF-2α activation in renal tubular cells upregulated mRNA and protein expressions of fibronectin and type 1 collagen associated with the activation of p38 mitogen-activated protein kinase. In CKD mice, activation of HIF-2α at the beginning of CKD significantly aggravated renal fibrosis, whereas it did not lead to renal dysfunction. However, activation at a late-stage of CKD abrogated both renal dysfunction and fibrosis, which was associated with restoration of renal vasculature and amelioration of hypoxia through increased renal tubular expression of VEGF and its isoforms. As with tubular cells with HIF-2α activation, those under hypoxia also upregulated VEGF, fibronectin, and type 1 collagen expressions associated with HIF-1α activation. In conclusion, late-stage renal tubular HIF-2α activation has protective effects on renal fibrosis and the resultant renal dysfunction, thus it could represent a therapeutic target in late stage of CKD.

The Relationship between Magnesium and Endothelial Function in End-Stage Renal Disease Patients on Hemodialysis.

PURPOSE: Chronic kidney disease (CKD) patients tend to have higher serum magnesium values than healthy population due to their positive balance of magnesium in kidney. Recent studies found that magnesium level is positively correlated with endothelial function. Therefore, this study was conducted to define the relationship between magnesium level and endothelial dysfunction in end stage renal disease (ESRD) patients on hemodialysis (HD). MATERIALS AND METHODS: A total of 27 patients were included in this cross-sectional study. Iontophoresis with laser-Doppler flowmetry, flow mediated dilation (FMD), and carotid intima-media thickness were measured. Patients' average serum magnesium levels were measured over previous three months, including the examination month. Pearson's correlation coefficient analysis and multivariate regression model were used to define the association between magnesium and endothelial function. RESULTS: In the univariate analysis, higher magnesium levels were associated with better endothelium-dependent vasodilation (EDV) of the FMD in ESRD patients on HD (r=0.516, p=0.007). When the participants were divided into two groups according to the median magnesium level (3.47 mg/dL), there was a significant difference in EDV of FMD (less than 3.47 mg/dL, 2.8±1.7%; more than 3.47 mg/dL, 5.1±2.0%, p=0.004). In multivariate analysis, magnesium and albumin were identified as independent factors for FMD (ß=1.794, p=0.030 for serum magnesium; ß=3.642, p=0.012 for albumin). CONCLUSION: This study demonstrated that higher serum magnesium level may be associated with better endothelial function in ESRD patients on HD. In the future, a large, prospective study is needed to elucidate optimal range of serum magnesium levels in ESRD on HD patients.

Technique failure in Korean incident peritoneal dialysis patients: a national population-based study.

BACKGROUND: Technique failure is an important issue for peritoneal dialysis (PD) patients. In this study, we aimed to analyze technique failure rate in detail and to determine the predictors for technique failure in Korea. METHODS: We identified all patients who had started dialysis between January 1, 2005, and December 31, 2008, in Korea, using the Korean Health Insurance Review and Assessment Service database. A total of 7,614 PD patients were included, and the median follow-up was 24.9 months. RESULTS: The crude incidence rates of technique failure in PD patients were 54.1 per 1,000 patient-years. The cumulative 1-, 2-, and 3-year technique failure rates of PD patients were 4.9%, 10.3%, and 15.6%, respectively. However, those technique failure rates by Kaplan-Meier analysis were overestimated compared with the values by competing risks analysis, and the differences increased with the follow-up period. In multivariate analyses, diabetes mellitus and Medical Aid as a crude reflection of low socioeconomic status were independent risk factors in both the Cox proportional hazard model and Fine and Gray subdistribution model. In addition, cancer was independently associated with a lower risk of technique failure in the Fine and Gray model. CONCLUSION: Technique failure was a major concern in patients initiating PD in Korea, especially in diabetic patients and Medical Aid beneficiaries. The results of our study offer a basis for risk stratification for technique failure.

AST-120 Improves Microvascular Endothelial Dysfunction in End-Stage Renal Disease Patients Receiving Hemodialysis.

PURPOSE: Endothelial dysfunction (ED) is a pivotal phenomenon in the development of cardiovascular disease (CVD) in patients receiving hemodialysis (HD). Indoxyl sulfate (IS) is a known uremic toxin that induces ED in patients with chronic kidney disease. The aim of this study was to investigate whether AST-120, an absorbent of IS, improves microvascular or macrovascular ED in HD patients. MATERIALS AND METHODS: We conducted a prospective, case-controlled trial. Fourteen patients each were enrolled in respective AST-120 and control groups. The subjects in the AST-120 group were treated with AST-120 (6 g/day) for 6 months. Microvascular function was assessed by laser Doppler flowmetry using iontophoresis of acetylcholine (Ach) and sodium nitroprusside (SNP) at baseline and again at 3 and 6 months. Carotid arterial intima-media thickness (cIMT) and flow-mediated vasodilation were measured at baseline and 6 months. The Wilcoxon rank test was used to compare values before and after AST-120 treatment. RESULTS: Ach-induced iontophoresis (endothelium-dependent response) was dramatically ameliorated at 3 months and 6 months in the AST-120 group. SNP-induced response showed delayed improvement only at 6 months in the AST-120 group. The IS level was decreased at 3 months in the AST-120 group, but remained stable thereafter. cIMT was significantly reduced after AST-120 treatment. No significant complications in patients taking AST-120 were reported. CONCLUSION: AST-120 ameliorated microvascular ED and cIMT in HD patients. A randomized study including a larger population will be required to establish a definitive role of AST-120 as a preventive medication for CVD in HD patients.

Effect of aldosterone on epithelial-to-mesenchymal transition of human peritoneal mesothelial cells.

BACKGROUND: Peritoneal fibrosis is one of the major causes of technical failure in patients on peritoneal dialysis. Epithelial-to-mesenchymal transition (EMT) of the peritoneum is an early and reversible mechanism of peritoneal fibrosis. Human peritoneal mesothelial cells (HPMCs) have their own renin-angiotensin-aldosterone system (RAAS), however, it has not been investigated whether aldosterone, an end-product of the RAAS, induces EMT in HPMCs, and which mechanisms are responsible for aldosterone-induced EMT. METHODS: EMT of HPMCs was evaluated by comparing the expression of epithelial cell marker, E-cadherin, and mesenchymal cell marker, α-smooth muscle actin after stimulation with aldosterone (1-100nM) or spironolactone. Activation of extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) and generation of reactive oxygen species (ROS) were assessed by western blotting and 2',7'-dichlorofluororescein diacetate staining, respectively. The effects of MAPK inhibitors or antioxidants (N-acetyl cysteine, apocynin, and rotenone) on aldosterone-induced EMT were evaluated. RESULTS: Aldosterone induced EMT in cultured HPMCs, and spironolactone blocked aldosterone-induced EMT. Aldosterone induced activation of both ERK1/2 and p38 MAPK from 1 hour. Either PD98059, an inhibitor of ERK1/2, or SB20358, an inhibitor of p38 MAPK, attenuated aldosterone-induced EMT. Aldosterone induced ROS in HPMCs from 5 minutes, and antioxidant treatment ameliorated aldosterone-induced EMT. N-acetyl cysteine and apocynin alleviated activation of ERK and p38 MAPK. CONCLUSION: Aldosterone induced EMT in HPMCs by acting through the mineralocorticoid receptor. Aldosterone-induced generation of ROS followed by activation of ERK, and p38 MAPK served as one of the mechanisms of aldosterone-induced EMT of HPMCs.

Improving survival rate of Korean patients initiating dialysis.

PURPOSE: The aim of this study was to investigate whether the survival rate among Korean dialysis patients changed during the period between 2005 and 2008 in Korea. MATERIALS AND METHODS: A total of 32357 patients who began dialysis between January 1, 2005 and December 31, 2008 were eligible for analysis. Baseline demographics, comorbidities, and mortality data were obtained from the database of the Health Insurance Review & Assessment Service. RESULTS: Kaplan-Meier curves according to the year of dialysis initiation showed that the survival rate was significantly different (log-rank test, p=0.005), most notably among peritoneal dialysis (PD) patients (p<0.001), although not among hemodialysis (HD) patients (p=0.497). In multivariate analysis, however, patients initiating either HD or PD in 2008 also had a significantly lower risk of mortality compared to those who began dialysis in 2005. Subgroup survival analysis among patients initiating dialysis in 2008 revealed that the survival rate of PD patients was significantly higher than that of HD patients (p=0.001), and the survival benefit of PD over HD remained in non-diabetic patients aged less than 65 years after adjustment of covariates. CONCLUSION: Survival of Korean patients initiating dialysis from 2005 to 2008 has improved over time, particularly in PD patients. In addition, survival rates among patients initiating dialysis in 2008 were different according to patients' age and diabetes, thus we need to consider these factors when dialysis modality should be chosen.