Sun Hee Park

Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy

To identify biomarker candidates associated with early IgA nephropathy (IgAN) and thin basement membrane nephropathy (TBMN), the most common causes presenting isolated hematuria in childhood, a proteomic approach of urinary exosomes from early IgAN and TBMN patients was introduced. The proteomic results from the patients were compared with a normal group to understand the pathophysiological processes associated with these diseases at the protein level. The urinary exosomes, which reflect pathophysiological processes, collected from three groups of young adults (early IgAN, TBMN, and normal) were trypsin‐digested using a gel‐assisted protocol, and quantified by label‐free LC‐MS/MS, using an MSE mode. A total of 1877 urinary exosome proteins, including cytoplasmic, membrane, and vesicle trafficking proteins, were identified. Among the differentially expressed proteins, four proteins (aminopeptidase N, vasorin precursor, α‐1‐antitrypsin, and ceruloplasmin) were selected as biomarker candidates to differentiate early IgAN from TBMN. We confirmed the protein levels of the four biomarker candidates by semi‐quantitative immunoblot analysis in urinary exosomes independently prepared from other patients, including older adult groups. Further clinical studies are needed to investigate the diagnostic and prognostic value of these urinary markers for early IgAN and TBMN. Taken together, this study showed the possibility of identifying biomarker candidates for human urinary diseases using urinary exosomes and might help to understand the pathophysiology of early IgAN and TBMN at the protein level.

Effect of Biocompatible Peritoneal Dialysis Solution on Residual Renal Function: A Systematic Review of Randomized Controlled Trials

♦ Introduction: Residual renal function (RRF) plays an important role in outcome of peritoneal dialysis (PD) including mortality. It is, therefore, important to provide a strategy for the preservation of RRF. The objective of this study was to evaluate relative protective effects of new glucose-based multicompartmental PD solution (PDS), which is well known to be more biocompatible than glucose-based conventional PDS, on RRF compared to conventional PDS by performing a systematic review (SR) of randomized controlled trials. ♦ Methods: We searched studies presented up to January 2014 in MEDLINE, EMBASE, the COCHRANE library, and local databases. Three independent reviewers reviewed and extracted prespecified data from each study. The random effects model, a more conservative analysis model, was used to combine trials and to perform stratified analyses based on the duration of follow-up. Study quality was assessed using the Cochrane Handbook for risk of bias. Eleven articles with 1,034 patients were identified for the SR. ♦ Results: The heterogeneity of the studies under 12 months was very high, and the heterogeneity decreased substantially when we stratified studies by the duration of follow-up. The mean difference of the studies after 12 months was 0.46 mL/min/1.73 m2 (95% confidence interval = 0.25 to + 0.67). ♦ Conclusion: New PDS showed the effect to preserve and improve RRF for long-term use compared to conventional PDS, even though it did not show a significant difference to preserve RRF for short-term use.

Effects of neutral pH and low-glucose degradation product-containing peritoneal dialysis fluid on systemic markers of inflammation and endothelial dysfunction: a randomized controlled 1-year follow-up study

BACKGROUNDnThe local peritoneal effects of low-glucose degradation product (GDP)-containing peritoneal dialysis fluid (PDF) have been extensively described. However, the systemic effects of prolonged prescription of these solutions are unknown. This study aimed to evaluate the effects of neutral pH and low-GDP PDF on systemic inflammation and endothelial dysfunction markers in peritoneal dialysis (PD) patients.nnnMETHODSnThis is a multicenter, open labeled, randomized controlled trial including one hundred fifty-two patients initiating continuous ambulatory peritoneal dialysis for end-stage renal disease from seven centers in Korea. Participants were randomly allocated to conventional PDF (Stay safe®; Fresenius Medical Care, Bad Homburg, Germany) or low-GDP PDF (Balance®; Fresenius Medical Care) and were followed for 1 year. Primary outcome variable was the inflammation and endothelial dysfunction index (IEDI), a composite score derived from serum levels of soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cellular adhesion molecule (sVCAM)-1 and high-sensitivity C-reactive protein (hs-CRP). sICAM-1, sVCAM-1, residual renal function (RRF), peritoneal membrane transport characteristics, ultrafiltration volume and nutritional parameters were measured as secondary outcome variables.nnnRESULTSnOf 152 patients randomized, 146 (low-GDP: conventional PDF, 79:67) patients entered the trial (46% male, 53% with diabetes mellitus). At 12-month follow-up, the low-GDP group had significantly lower levels of IEDI, sICAM-1 and sVCAM-1 compared to the conventional group; hs-CRP was not different between groups. Peritoneal transport characteristics, RRF, nutritional parameters, incidence of peritonitis and death-censored technique survival were not different between groups.nnnCONCLUSIONnNeutral pH and low-GDP PDF likely produce fewer changes in markers of endothelial dysfunction compared to conventional PDF in incident PD patients.

Successful withdrawal of antiviral treatment in kidney transplant recipients with chronic hepatitis B viral infection.

The optimal duration of antiviral therapy for kidney transplant recipients (KTR) with chronic hepatitis B virus (HBV) infection remains unclear. We reported the long‐term outcomes after withdrawal of antiviral agent in KTR with chronic HBV infection.

Left Ventricular Strain as Predictor of Chronic Aortic Regurgitation

Background It is not well known about the implication of left ventricular (LV) strain as a predictor for mortality in patients with chronic aortic regurgitation (AR). The purpose of this study was to investigate whether global longitudinal strain measured by two-dimensional speckle-tracking echocardiography could predict long-term outcome in patients with chronic AR. Methods This is a single center non-randomized retrospective observational study. The patients with chronic AR from January 2002 to December 2012 were retrospectively enrolled. Following patients were excluded; combined other significant valvular disease, previous heart surgery, aortic disease, congenital heart disease, acute AR and young age under 18 years old. Finally, 60 patients were analyzed and the LV global strain rate was measured on apical four chamber image (GS-4CH). Results During 64 months follow-up duration, 16 patients (26.7%) were deceased and 38 patients (63.3%) underwent aortic valve replacement (AVR). Deceased group was older (69 years old vs. 51 years old, p < 0.001) and had lower longitudinal strain (-12.05 ± 3.72% vs. -15.66 ± 4.35%, p = 0.005). Kaplan-Meier survival curve stratified by GS-4CH showed a trend of different event rate (log rank p = 0.001). On multivariate analysis by cox proportional hazard model adjusting for age, sex, body surface area, history of atrial fibrillation, blood urea nitrogen, LV dilatation, LV ejection fraction and AVR, decreased GS-4CH proved to be an independent predictor of mortality in patients with chronic AR (hazard ratio 1.313, 95% confidence interval 1.010-1.706, p = 0.042). Conclusion GS-4CH may be a useful predictor of mortality in patient with chronic AR.

Systemic and Local Impact of Glucose and Glucose Degradation Products in Peritoneal Dialysis Solution

The main osmotic agent used in the peritoneal dialysis (PD) solution is glucose because of its great osmotic power, simple metabolism, and safety. Once into the systemic circulation, however, glucose can be a cause for metabolic complications including hyperglycemia, obesity, and dyslipidemia. The glucose absorbed from peritoneal cavity leads to insulin resistance and hyperglycemia, which is associated with oxidative stress. Long-term exposure of peritoneal membrane to glucose in PD solution also has local effects such as functional and structural changes leading to peritoneal membrane failure. Moreover, the intraperitoneal glucose absorption induces conditions similar to postprandial hyperglycemia, which is a proven independent risk factor of coronary artery disease in patients with type 2 diabetes. Though speculative, glucose toxicity might explain a higher mortality of PD patients after the first few years compared with those on hemodialysis. Glucose degradation products (GDPs) induce apoptosis of peritoneal mesothelial cells (PMCs), renal tubular epithelial cells, and endothelial cells, and facilitating epithelial mesenchymal transition of PMCs. GDPs provide a stronger reactivity than glucose in the formation of advanced glycation end-products, a known cause for microvascular complications and arteriosclerosis. Unfortunately, clinical studies using a low-GDP PD solution have provided mixed results on the residual renal function, peritonitis, peritoneal membrane function, and mortality; consistent outcome data are not readily available at present.

Complication Rate of Transfemoral Endomyocardial Biopsy with Fluoroscopic and Two-dimensional Echocardiographic Guidance: A 10-Year Experience of 228 Consecutive Procedures

Endomyocardial biopsy (EMB) is one of the reliable methods for the diagnosis of various cardiac diseases. However, EMB can cause various complications. The purpose of this study is to evaluate the complication of transfemoral EMB with both fluoroscopic and two-dimensional (2-D) echocardiographic guidance. A total of 228 patients (148 men; 46.0±14.6 yr-old) who underwent EMB at Kyungpook National University Hospital from January 2002 to June 2012 were included. EMB was performed via the right femoral approach with the guidance of both echocardiography and fluoroscopy. Overall, EMB-related complications occurred in 21 patients (9.2%) including one case (0.4%) with cardiac tamponade requiring emergent pericardiocentesis, four cases (1.8%) with small pericardial effusion without pericardiocentesis, two cases (0.9%) with hemodynamically unstable ventricular tachycardia (VT), one case (0.4%) with nonsustained VT, one case (0.4%) with tricuspid regurgitation, twelve cases (5.3%) with right bundle branch block. There was no occurrence of either EMB-related death or cardiac surgery. Left ventricular ejection fraction was significantly lower (32.0±18.7% vs 42.0±19.1%, P=0.023) and left ventricular end-diastolic dimension was larger (60.0±10.0 mm vs 54.2±10.2 mm, P=0.013) in patients with EMB related complications than in those without. It is concluded that transfemoral EMB with fluoroscopic and 2-D echocardiographic guidance is a safe procedure with low complication rate.

The Prevalence, Association, and Clinical Outcomes of Frailty in Maintenance Dialysis Patients

OBJECTIVEnTo investigate the clinical implications of frailty in chronic kidney disease patients undergoing maintenance hemodialysis and chronic peritoneal dialysis.nnnDESIGNnIn this prospective study, all of the participants completed the Short Form of the Kidney Disease Quality of Life questionnaire, Korean version, to determine their frailty phenotype. We also obtained blood chemistry and demographic data at enrollment. Data regarding the history of hospitalization and death were collected during the follow-up period.nnnSUBJECTSnWe recruited 1,658 patients (1,255 maintenance hemodialysis and 403 chronic peritoneal dialysis) from multidialysis units (nxa0=xa027). We excluded patients who had been hospitalized in the previous 3xa0months.nnnMAIN OUTCOME MEASURESnHospitalization and survival rate during study period.nnnRESULTSnThe participants mean age was 55.2xa0±xa011.9xa0years old, and 55.2% were male. Among the participants, 34.8% were rated as frail and 45.7% as prefrail. Multivariate analysis demonstrated significant associations of frailty with age, comorbidity, disability, unemployment, higher body mass index, and a lower educational level. During the follow-up period (median 17.1xa0months), 608 patients (79 not frail, 250 prefrail, and 279 frail) were hospitalized, and 87 patients (10 not frail, 24 prefrail, and 53 frail) died (Pxa0<xa0.001). Frailty was associated with hospitalization (adjusted hazard ratio, 1.80; 95% confidence interval: 1.38-2.36) and mortality (hazard ratio, 2.37, 95% confidence interval: 1.11-5.02).nnnCONCLUSIONnThe frailty phenotype was common even in, prevalent end-stage renal disease patients on dialysis, and was significantly associated with higher rates of hospitalization and mortality.

Interleukin‐18, transforming growth factor‐β, and vascular endothelial growth factor gene polymorphisms and susceptibility to primary glomerulonephritis

Several studies have showed an association of gene polymorphisms with the development of glomerulonephritis (GN). We investigated the effects of gene polymorphisms on the development of GN by analyzing polymorphisms in the interleukin (IL)-18, transforming growth factor (TGF)-β, and vascular endothelial growth factor (VEGF) genes in Korean patients with primary GN. The study included 146 normal subjects (controls) and 100 patients diagnosed with primary GN by kidney biopsy. The gene polymorphisms A-607C and G-137C in IL-18, C-509T and T869C in TGF-β1, and C-2578A and C405G in VEGF were investigated in DNA extracted from peripheral blood. Significant differences were observed between the GN and control groups in the genotype and allele frequencies of A-607C IL-18 and C405G VEGF. The frequencies of the IL-18-607CC genotype [P = 0.001, odds ratio (OR) = 2.473] and the VEGF 405GG genotype (P = 0.001, OR = 2.473) were significantly increased in the GN group. The combination of IL-18-607CC+ and VEGF 405GG+ genotypes had a higher risk for developing GN in comparison with the combination of IL-18-607CC- and VEGF 405GG- genotypes (P < 0.001, OR = 8.642). In the haplotype analysis of the IL-18 gene, the CG haplotype was significantly more frequent in the GN group than the control group (61.5% vs 46.9%, P = 0.002). These results show that the -607CC genotype of the IL-18 gene and the 405GG genotype of the VEGF gene are associated with susceptibility to and the development of primary GN.

A new tool for the risk stratification of patients undergoing primary percutaneous coronary intervention with ST-segment elevation myocardial infarction: Bio-Clinical SYNTAX score

0.80 0.33–1.90 0.607 1.13 0.43–2.94 0.804 Killip class N1 1.06 0.49–2.27 0.891 0.91 0.40–2.04 0.808 Diabetes mellitus 0.78 0.34–1.80 0.562 0.62 0.24–1.61 0.329 Hyperlipidemia 0.58 0.22–1.54 0.275 0.60 0.22–1.65 0.320 Current smoking 0.89 0.39–2.02 0.774 0.71 0.30–1.70 0.443 Hemoglobin 0.83 0.67–1.02 0.078 0.83 0.67–1.03 0.096 Uric acid 1.14 0.98–1.33 0.082 1.13 0.95–1.35 0.166 Log hs-CRP 1.39 1.12–1.72 0.003 1.35 1.08–1.69 0.008 Log Bio-CSS 2.91 1.52–5.55 0.001 2.79 1.41–5.52 0.003 Beta-blockers 1.64 0.33–8.29 0.549 ACE-I/ARBs 0.37 0.09–1.48 0.159 Statins 0.49 0.17–1.44 0.197