Jun Young Do

Independent Effects of Systemic and Peritoneal Inflammation on Peritoneal Dialysis Survival

Systemic inflammation, as evidenced by elevated inflammatory cytokines, is a feature of advanced renal failure and predicts worse survival. Dialysate IL-6 concentrations associate with variability in peritoneal small solute transport rate (PSTR), which has also been linked to patient survival. Here, we determined the link between systemic and intraperitoneal inflammation with regards to peritoneal membrane function and patient survival as part of the Global Fluid Study, a multinational, multicenter, prospective, combined incident and prevalent cohort study (n=959 patients) with up to 8 years of follow-up. Data collected included patient demographic characteristics, comorbidity, modality, dialysis prescription, and peritoneal membrane function. Dialysate and plasma cytokines were measured by electrochemiluminescence. A total of 426 survival endpoints occurred in 559 incident and 358 prevalent patients from 10 centers in Korea, Canada, and the United Kingdom. On patient entry to the study, systemic and intraperitoneal cytokine networks were dissociated, with evidence of local cytokine production within the peritoneum. After adjustment for multiple covariates, systemic inflammation was associated with age and comorbidity and independently predicted patient survival in both incident and prevalent cohorts. In contrast, intraperitoneal inflammation was the most important determinant of PSTR but did not affect survival. In prevalent patients, the relationship between local inflammation and membrane function persisted but did not account for an increased mortality associated with faster PSTR. These data suggest that systemic and local intraperitoneal inflammation reflect distinct processes and consequences in patients treated with peritoneal dialysis, so their prevention may require different therapeutic approaches; the significance of intraperitoneal inflammation requires further elucidation.

Association of Visceral Fat Area with Chronic Kidney Disease and Metabolic Syndrome Risk in the General Population: Analysis Using Multi-Frequency Bioimpedance

Background/Aims: Advances in bioimpedance analysis (BIA) technologies now enable visceral fat area (VFA) to be assessed using this method. The aim of this study was to evaluate the clinical relevance and usefulness of VFA as a predictor of chronic kidney disease (CKD) and metabolic syndrome (MS), using BIA. Methods: We identified 24,791 adults who underwent voluntary routine health checkups at Yeungnam University Hospital. In total 22,480 patients were recruited into our study. Participants were divided into 3 tertiles based on their VFA: low, middle, and high tertiles. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2. Results: The higher tertile of VFA was associated with a higher prevalence of diabetes mellitus, hypertension, and male sex. Waist-to-hip ratio, body mass index, blood pressure, lean mass, body fat %, and fasting glucose, total cholesterol, triglyceride, GGT, AST, ALT, and uric acid levels all increased as the VFA tertile increased (P < 0.001 for all variables). The prevalence of CKD was 6.9% in the low tertile, 13.9% in the middle tertile, and 25.2% in the high tertile (P < 0.001). The prevalence of MS was 2.2% in the low tertile, 12.8% in the middle tertile, and 36.7% in the high tertile (P < 0.001). The AUROC values for VFA were higher than those for BMI and WHR. For VFA, the sensitivity and specificity for predicting CKD were 62.66% (95% CI, 61.0-64.3) and 64.22% (95% CI, 63.5-64.9), respectively, and 77.65% (95% CI, 76.3-79.0), and 68.81% (95% CI, 68.1-69.5), respectively for predicting MS. Conclusion: Our results demonstrated that the VFA, measured by BIA, is a simple method for predicting the risk of CKD and MS.

Risk Factors for Mortality in Stable Peritoneal Dialysis Patients

Background: The mortality rates of end-stage renal disease patients have significantly declined over the past decade. However, there are few reports on the risk factors for mortality in stable peritoneal dialysis (PD) patients who survive for a considerable time. Patients and methods: We reviewed the medical records and identified all adult patients who received PD between April 2001 and March 2009 in our institution. The total cohort was 550 patients. Among these patients, 383 patients were enrolled as stable PD patients. Results: The cumulative survival of the stable PD patients was 91.6% at 3 years and 78.7% at 5 years. On univariate analysis, old age (≥65 years of age), hypoalbuminemia (<35 g/L), log C-reactive protein (CRP) (≥0.84), phosphorus (<1.13 mmol/L), statin, icodextrin, and the Davies index were associated with mortality for all PD patients. Old age, hypoalbuminemia, log CRP, phosphorus, the residual renal function (RRF) (≤4 mL/min/1.73 m2) at 24 months, renin–angiotensin system blockade, icodextrin, and the Davies index were associated with mortality for the stable PD patients. Multivariate analysis showed that, among the variables, age, log CRP, phosphorus, initial RRF, and the Davies index were associated with mortality for all PD patients. In stable PD patients, age, log CRP, phosphorus, RRF at 24 months, and the Davies index were associated with mortality. Conclusion: Initial high RRF combined with the RRF preservation, maintenance of proper phosphorus, control of inflammation, and proper management of comorbidities may help to improve the survival of PD patients including stable PD patients.

Comparison of bioimpedance analysis and dual-energy X-ray absorptiometry body composition measurements in peritoneal dialysis patients according to edema.

BACKGROUND Changes in the difference between bioimpedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA) body composition measurements according to edema is an important issue for peritoneal dialysis (PD) patients. METHODS We reviewed the medical records of patients to identify all adults who had undergone PD and composition measurements by both BIA and DXA techniques. The aim of this study was to evaluate any change in the difference between BIA and DXA body composition measurements according to edema. RESULTS We identified 409 patients whose body compositions were measured by both techniques one or more times, for a total of 1,109 pairs of measurements. The measurements were divided into 4 quartiles on the basis of the edema index. Significant correlations and intraclass correlations were noted between the two methods for lean mass (LM), fat mass (FM), and bone mineral content. Simple linear regression analyses using DXA measurements for the prediction of body compositions by BIA showed that non-standardized-βs of total LM decreased as the grade of edema index increased (from 1.008 to 0.949), whereas non-standardized-βs of total FM increased as the grade of edema index increased (from 1.034 to 1.162). Bias for total LM changed from positive to negative, and this negative bias amplified as the grade of edema index escalated (from 0.406 kg to -2.276 kg). A positive bias was observed for total FM in the 1st quartile, and this positive bias increased with an increase in the grade of edema index (from 0.594 kg to 2.863 kg). CONCLUSION LM measured by DXA is overestimated in PD patients with edema compared to the measurements by BIA. However, FM and bone mineral content measured by BIA are is overestimated in PD patients, compared to the measurements by DXA, especially in patients with worsening edema. The difference between the two techniques grows more prominent as the grade of edema increases. A combination of two methods will allow clinicians to conduct more accurate body composition assessments for PD patients with edema.

Paricalcitol Ameliorates Epithelial-to-Mesenchymal Transition in the Peritoneal Mesothelium

Background: The purpose of the present study was to examine the effectiveness of paricalcitol for the prevention of epithelial-to-mesenchymal transition (EMT). Materials and Methods: Human peritoneal mesothelial cells (HPMCs) were cultured in media containing transforming growth factor β1 (TGF-β1) with or without paricalcitol. Forty-two male Sprague-Dawley rats were divided into three groups. In the control group, the catheter was inserted but no dialysate was infused. The peritoneal dialysis (PD) group was infused with a conventional 4.25% dialysis solution. The paricalcitol group was infused with 4.25% dialysis solution and cotreated with paricalcitol. Results: Exposure of HPMCs to TGF-β1 decreased the protein level of the epithelial cell marker and increased the expression levels of the mesenchymal markers. Cotreatment with paricalcitol increased the protein levels of the epithelial cell marker and decreased those of mesenchymal markers compared with their levels in cells treated with TGF-β1 alone. Exposure of HPMCs to TGF-β1 significantly increased the phosphorylation of Smad2 and Smad3. Cotreatment with paricalcitol significantly decreased the phosphorylation of Smad2 and Smad3 compared with that of cells treated with TGF-β1 alone. After 8 weeks of experimental PD in rats, the thickness of the peritoneal membrane in the PD group was significantly increased compared with that of the control group. Cotreatment with paricalcitol decreased peritoneal thickness. Conclusion: The present study showed that paricalcitol attenuates the TGF-β1-induced EMT in peritoneal mesothelial cells. We suggest that paricalcitol may preserve peritoneal mesothelial cells during PD and could thus be of value for the success of long-term PD.

Proteinuria as a Risk Factor for Decline in Residual Renal Function in Non-Diabetic Peritoneal Dialysis Patients

Background: Preservation of residual renal function (RRF) is a major issue for patients on peritoneal dialysis (PD). Whether proteinuria is associated with a decline in RRF in patients on PD remains unclear. Patients and Methods: We reviewed the medical records at the Yeungnam University Hospital in Korea and identified patients who started PD between June 1995 and August 2011. A total of 147 non-diabetic patients were enrolled in the study. The patients were divided into 3 groups with respect to the tertile of initial proteinuria level: Low (n = 49; <320 mg/day), Middle (n = 49; 320-822 mg/day), and High groups (n = 49; >822 mg/day). Results: The mean patient age was 50.2 ± 15.0 years in the Low tertile, 50.2 ± 15.4 years in the Middle tertile, and 49.0 ± 15.1 years in the High tertile. Decline in RRF during follow-up period was greater in the High tertile than that in the other tertiles (P = 0.001). The proportion of patients with RRF >50% of baseline at 24 months after the initiation of PD was 83% in the Low tertile, 66% in the Middle tertile, and 40% in the High tertile (P < 0.001). The multivariate analysis after adjusting for initial RRF, age, gender, underlying disease of end-stage renal disease except diabetes mellitus, PD modality, use of icodextrin, PD-associated peritonitis, and tertile of the initial proteinuria level revealed that High tertile of the initial proteinuria level was associated with a decline in RRF (hazard ratios: 2.442 for the Middle tertile, P = 0.007 ; 3.713 for the Low tertile, P < 0.001). Conclusion: The present study demonstrates that proteinuria may be is associated with a rapid decline in RRF in non-diabetic patients on PD, although the potential role of additional factors should be further investigated in prospective studies.

Whole blood versus serum ionized calcium concentrations in dialysis patients

Background/Aims The aim of this study is to measure the difference of ionized calcium between heparinized whole blood and serum. Methods We recruited 107 maintenance hemodialysis (HD) patients from our hospital HD unit. The clinical and laboratory data included ionized calcium in serum and in whole blood (reference, 4.07 to 5.17 mg/dL). Results The level of ionized calcium in serum was higher than that in whole blood (p < 0.001). Bland-Altman analysis showed that difference for ionized calcium was 0.5027. For the difference, the nonstandardized β was -0.4389 (p < 0.001) and the intercept was 2.2418 (p < 0.001). There was a significant difference in the distribution of categories of ionized calcium level between two methods (κ, 0.279; p < 0.001). Conclusions This study demonstrates that whole blood ionized calcium is underestimated compared with serum ionized calcium. Positive difference increases as whole blood ionized calcium decreases. Therefore, significant hypocalcemia in whole blood ionized calcium should be verified by serum ionized calcium.

Visceral Fat Area Determined Using Bioimpedance Analysis Is Associated with Hearing Loss.

Background: Visceral fat area (VFA) using bioimpedance analysis (BIA) as a simple analyzer can be used to assess VFA, which may be associated with HL. The aim of the present study was to evaluate the clinical relevance and usefulness of VFA using BIA as a predictor of HL. Patients and Methods: In total, 18,415 patients were recruited into our study. VFAs were measured using multi-frequency BIA. VFAs were normalized by body mass index (BMI). Participants were divided into 3 tertiles based on their VFA/BMI for both sexes. For both ears of each participant, the low-frequency (Low-Freq), mid-frequency (Mid-Freq), and high-frequency (High-Freq) values were obtained calculating the pure tone averages at 0.5 and 1 kHz, 2 and 3 kHz, and 4 and 6 kHz, respectively. The average hearing threshold (AHT) was calculated as the pure tone average at the 4 frequencies (i.e., 0.5, 1, 2, and 3 kHz). HL was defined as AHT >40 dB. Results: The VFA/BMI had the greatest AUROC among VFA, BMI, and VFA/BMI in both sexes in this study. In both univariate and multivariate analyses, VFA/BMI tertiles were associated with all 4 hearing thresholds (i.e., Low-Freq, Mid-Freq, High-Freq, and AHT). The 4 hearing thresholds were positively correlated with VFA/BMI as a continuous variable. The odds ratio for HL increased as the VFA/BMI tertile increased. Conclusion: VFA/BMI was associated with hearing impairment in the Asian population. The participants with high VFA/BMI should be closely monitored for hearing impairment.

Acute kidney injury due to sodium bromate intoxication: a report of two cases.

Sodium bromate is a strong oxidant used as a neutralizing solution in hair permanents, as well as an auxiliary agent in printing and dyeing. Accidental or deliberate ingestion of bromate solution has rarely been reported in Korea. The clinical manifestations of bromate intoxication are vomiting, diarrhea, central nervous system symptoms, oliguric or non-oliguric acute kidney injury, hemolytic anemia, and deafness; most of these manifestations are reversible, with the exception of renal failure and deafness. Here, we report on two patients who demonstrated distinct clinical progressions. In the first case, a 16-year-old woman was successfully treated with hemodialysis and recovered renal function without hearing loss. However, in the second case, delayed hemodialysis resulted in persistent renal failure and hearing loss in a 77-year-old woman. This suggests that emergency therapeutic measures, including hemodialysis, should be taken as soon as possible, as the rapid removal of bromate may be essential to preventing severe intoxication and its sequelae.

The Clinical Significance of Physical Activity in Maintenance Dialysis Patients

Background: The aim of the present study was to evaluate the effects of physical activity on various aspects in Asian dialysis patients. Methods: This was a retrospective cohort study. Study participants were recruited from 27 hospitals or dialysis centers in Korea (n = 1611). The participants were divided into 3 groups according to the degree of regular exercise: Inactive group, Intermediate group, and Active group. Results: The proportions of patients with frailty and the presence of each component decreased as physical activity increased. The presence and numbers of disabilities decreased as physical activity increased. The number of participants with a history of fall during the last 12 months was 149 (20.5%) in the Inactive group, 88 (16.9%) in the Intermediate group, and 48 (13.2%) in the Active group. Physical component scale and mental component scale scores increased as physical activity increased. The survival rate for all-cause death at 500 days was 95.5% in the Active group, 95.2% in the Intermediate group, and 93.5% in the Inactive group. Conclusion: High physical activity was associated with favorable results for most health-related quality of life scale scores, including frailty, disability, and exhaustion, in Korean dialysis patients.