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.

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.

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 (β=1.794, p=0.030 for serum magnesium; β=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.

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 (β=1.794, p=0.030 for serum magnesium; β=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.

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, alpha-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.

Development of Metabolic Acidosis after Neobladder Reconstruction / 이화의대지

OBJECTIVES: Metabolic acidosis frequently develops in patients after neobladder reconstruction. However, the incidence of metabolic acidosis in patients with neobladder and the factors associated with the development of metabolic acidosis have not been well elucidated. We aimed to investigate the incidence and the potential predictors for the development of metabolic acidosis after neobladder reconstruction with intestinal segment. METHODS: We included patients who underwent neobladder reconstruction using intestinal segment at Ewha Womans University Mokdong Hospital between January 1, 2005 and December 31, 2014. A subgroup of patients according to the time of metabolic acidosis occurrence was further analyzed in order to characterize predictors for metabolic acidosis. RESULTS: Metabolic acidosis was encountered in 79.4% of patients with neobladder during follow up period. When patients were divided into 2 groups according to anion gap (AG), total CO2 (18.9+/-2.1 mEq/L vs. 20.0+/-1.3 mEq/L, P=0.001) and chloride (106.6+/-4.9 mE/L vs. 109.4+/-3.6 mEq/L, P12 and AG< or =12. Furthermore, when patients were divided into 3 groups; patients with metabolic acidosis at postoperative day (POD) 1; from POD 2 to 14 days; after 14 days, there was significant difference among those subgroups. CONCLUSION: Our study showed the rate of metabolic acidosis in patients underwent neobladder reconstruction and the difference between patients with metabolic acidosis and those without metabolic acidosis for the first time in Korea. In the future, well designed prospective study will be needed to prevent metabolic acidosis after neobladder reconstruction.

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.

Rapid Decrease of Intact Parathyroid Hormone Could Be a Predictor of Better Response to Cinacalcet in Hemodialysis Patients

PURPOSE: Cinacalcet is effective for treating refractory secondary hyperparathyroidism (SHPT), but little is known about the response rates and clinical factors influencing the response. MATERIALS AND METHODS: A prospective, single-arm, multi-center study was performed for 24 weeks. Cinacalcet was administered to patients with intact parathyroid hormone (iPTH) level greater than 300 pg/mL. Cinacalcet was started at a dose of 25 mg daily and titrated until 100 mg to achieve a serum iPTH level <300 pg/mL (primary end point). Early response to cinacalcet was defined as a decrease of iPTH more than 50% within one month. RESULTS: Fifty-seven patients were examined. Based on the magnitude of iPTH decrease, patients were divided into responder (n=47, 82.5%) and non-responder (n=10, 17.5%) groups. Among the responders, 38 achieved the primary end point, whereas 9 patients showed a reduction in serum iPTH of 30% or more, but did not reach the primary end point. Compared to non-responders, responders were significantly older (p=0.026), female (p=0.041), and diabetics (p<0.001). Additionally, early response was observed more frequently in the responders (30/47, 63.8%), of whom the majority (27/30, 90.0%) achieved the primary end point. Multivariate analysis showed that lower baseline iPTH levels [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93-0.99], the presence of diabetes (OR 46.45, CI 1.92-1125.6) and early response (OR 21.54, CI 2.94-157.7) were significant clinical factors affecting achievement of iPTH target. CONCLUSION: Cinacalcet was effective in most hemodialysis patients with refractory SHPT. The presence of an early response was closely associated with the achievement of target levels of iPTH.

A case of membranoproliferative glomerulonephritis associated with metastatic colon cancer

No abstract available.

Association between vascular access failure and microparticles in hemodialysis patients

BACKGROUND: Vascular access failure, a major cause of morbidity in hemodialysis (HD) patients, occurs mainly at stenotic endothelium following an acute thrombotic event. Microparticles (MPs) are fragments derived from injured cell membrane and are closely associated with coagulation and vascular inflammatory responses. METHODS: We investigated the relationship between levels of circulating MPs and vascular access patency in HD patients. A total of 82 HD patients and 28 healthy patients were enrolled. We used flow cytometry to measure endothelial MPs (EMPs) identified by CD31+CD42- or CD51+ and platelet-derived MPs (PMPs) identified by CD31+CD42+ in plasma samples of participants. Vascular access patency was defined as an interval from the time of access formation to the time of first access stenosis in each patient. MP counts were compared according to access patent duration. RESULTS: The levels of EMP (both CD31+CD42- and CD51+) and CD31+CD42+PMP were significantly higher in patients than in healthy participants. Levels of CD31+CD42-EMP and CD31+CD42+PMP showed a positive correlation. In nondiabetic HD patients, CD31+CD42-EMPs and CD31+CD42+PMPs were more elevated in the shorter access survival group (access survival or = 4 years). CONCLUSION: Elevated circulating EMP or PMP counts are influenced by end-stage renal disease and increased levels of EMP and PMP may be associated with vascular access failure in HD patients.

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) > or = 60 mL/min/1.73 m2. 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.

A More Appropriate Cardiac Troponin T Level That Can Predict Outcomes in End-Stage Renal Disease Patients with Acute Coronary Syndrome

PURPOSE: Cardiac troponin T (cTnT), a useful marker for diagnosing acute myocardial infarction (AMI) in the general population, is significantly higher than the usual cut-off value in many end-stage renal disease (ESRD) patients without clinically apparent evidence of AMI. The aim of this study was to evaluate the clinical usefulness of cTnT in ESRD patients with acute coronary syndrome (ACS). MATERIALS AND METHODS: Two hundred eighty-four ESRD patients with ACS were enrolled between March 2002 and February 2008. These patients were followed until death or June 2009. Medical records were reviewed retrospectively. The cut-off value of cTnT for AMI was evaluated using a receiver operating characteristic (ROC) curve. We calculated Kaplan-Meier survival curves, and potential outcome predictors were determined by Cox proportional hazard analysis. RESULTS: AMIs were diagnosed in 40 patients (14.1%). The area under the curve was 0.98 in the ROC curve (p or =0.35 ng/mL compared to the other groups. Initial serum cTnT concentration was an independent predictor for mortality. CONCLUSION: Because ESRD patients with an initial cTnT concentration > or =0.35 ng/mL have a poor prognosis, it is suggested that urgent diagnosis and treatment be indicated in dialysis patients with ACS when the initial cTnT levels are > or =0.35 ng/mL.

Hydration Status in Elderly Hemodialysis Patients: Bioimpedance Analysis / 대한신장학회지

PURPOSE: This study was aimed to compare hydration status between young and elderly end-stage renal disease (ESRD) patients on hemodialysis (HD) and to analyze factors related to overhydration. METHODS: We measured fluid status before a mid-week HD session in clinically stable 47 patients on maintenance HD using bioimpedance spectroscopy (BIS) device. In addition, weight and blood pressure (BP) were recorded during the treatment. RESULTS: Participants were divided into young ( or =65 years, n=15) patients. In elderly patients, pre-HD diastolic BP, intracellular water (ICW), and lean tissue index (LTI) were significantly lower and extracellular water (ECW)/total body water (TBW) was significantly higher than in young patients. However, there were no differences in pre-HD body mass index (BMI), ultrafiltration volume, pre-HD systolic BP, TBW, ECW, and fat tissue index between the two groups. ECW/TBW ratio and LTI were significantly correlated with age. In a multivariate regression analysis, age and pre-HD pulse pressure were significantly associated with ECW/TBW. CONCLUSION: Although BMI and TBW of elderly ESRD patients were similar to those of young patients, ICW and LTI were lower and ECW/TBW was higher in elderly patients than in young patients. Therefore, clinical manifestations related to overhydration may develop more frequently in elderly patients compared with young patients.

Serum Globotriaosylceramide Assay as a Screening Test for Fabry Disease in Patients with ESRD on Maintenance Dialysis in Korea

BACKGROUND/AIMS: Fabry disease is an X-linked recessive and progressive disease caused by alpha-galactosidase A (alpha-GaL A) deficiency. We sought to assess the prevalence of unrecognized Fabry disease in dialysis-dependent patients and the efficacy of serum globotriaosylceramide (GL3) screening. METHODS: A total of 480 patients of 1,230 patients among 17 clinics were enrolled. Serum GL3 levels were measured by tandem mass spectrometry. Additionally, we studied the association between increased GL3 levels and cardiovascular disease, cerebrovascular disease, or left ventricular hypertrophy. RESULTS: Twenty-nine patients had elevated serum GL3 levels. The alpha-GaL A activity was determined for the 26 patients with high GL3 levels. The mean alpha-GaL A activity was 64.6 nmol/hr/mg (reference range, 45 to 85), and no patient was identified with decreased alpha-GaL A activity. Among the group with high GL3 levels, 15 women had a alpha-GaL A genetics analysis. No point mutations were discovered among the women with high GL3 levels. No correlation was observed between serum GL3 levels and alpha-GaL A activity; the Pearson correlation coefficient was 0.01352 (p = 0.9478). No significant correlation was observed between increased GL3 levels and the frequency of cardiovascular disease or cerebrovascular disease. CONCLUSIONS: Fabry disease is very rare disease in patients with end-stage renal disease. Serum GL3 measurements as a screening method for Fabry disease showed a high false-positive rate. Thus, serum GL3 levels determined by tandem mass spectrometry may not be useful as a screening method for Fabry disease in patients with end stage renal disease.

Factors Affecting Production of C-reactive Protein in Vascular Smooth Muscle Cells / 대한신장학회지

PURPOSE:The stenosis of vascular access for hemodialysis is caused by neointimal hyperplasia with the proliferation of vascular smooth muscle cells (SMC) as a prominent feature. C-reactive protein (CRP) is known to be produced in vascular SMC and can promote SMC proliferation. However, it is unclear of which factors regulate CRP production in neointimal hyperplasia. In the present study, we evaluated the factors affecting production of CRF in aortic SMC. METHODS:Human aortic SMC were cultured in a American type culture collection (ATCC) medium containing 10% FBS. Platelet-derived growth factor (PDGF) (10, 100 ng/mL), interferon-gamma(INF-gamma (1, 10, 100 ng/mL), hydroxymethylglutaryl-coA reductase inhibitor (lovastatin) (10 ?M/L) were added. After 72 hours, the level of CRP in SMC was measured by Western blot analysis and cell proliferation was assessed by MTT dye reduction assay. We used RT-PCR to observe PDGF receptor expression in SMC. RESULTS:Both INF-gammaand PDGF were found to stimulate CRP production and SMC proliferation. In contrast, lovastatin inhibited PDGF or INF-gammainduced CRP production and SMC proliferation. The expression of PDGF receptor-alphain aortic SMC was increased after treatment of 100 ng/mL of IFN-gamma CONCLUSION:SMC proliferation and CRP production in SMC are stimulated by PDGF or INF-gammaand inhibited by statin.

A case of leprosy associated with bone marrow involvement and renal failure / 대한내과학회지

Leprosy is caused by acid fast bacilli (AFB). It usually affects the skin, nerve segments close to the skin, and mucous membranes of the upper respiratory tract. However, it can also involve other areas including lymph nodes, bone marrow, liver, and spleen. A 75-year-old male was admitted to hospital with general edema and dizziness, accompanied by pancytopenia and renal failure. The bone marrow biopsy showed a marke increased in histiocytes and copious blue-gray fine debris containing AFB on special staining. He was diagnosed with lepromatous leprosy. We report a case of lepromatous leprosy that manifested as chronic renal failure and bone marrow involvement.

Continuous Monitoring of Donor Specific Anti-HLA Antibody in Kidney Transplantation Patients / 대한이식학회지

BACKGROUND: A positive reaction at flow cytometry crossmatch (FCXM) has been highlighted by its predictive value for clinical outcome in kidney transplantation after accumulation of large clinical data. The detection of de novo development of anti-HLA antibodies after transplantation is associated with increased rejection and decreased graft survival. In this study, we report the experience for the detection of anti-donor specific antibody (DSA) by more sensitive FCXM methods in renal transplantation patients. METHODS: T and B cell FCXMs were performed on 11 pretransplant and 51 posttransplant sera from 11 patients who received renal grafts between 2004 and 2005. The posttransplant sera were collected in specific and regular intervals from posttranspant 1 week to 1 year. RESULTS: Among 62 sera, four (7.8%) from 2 patients showed positive FCXM. In one patient, pretransplant serum which was negative at previous CDCXM, and 2 consecutive sera collected at 1 week and 1 month after transplantation were positive at FCXM. And the antibody identified was B51 which was specific for one of donor alleles (DSA). In another patient, FCXM became positive 1 week after transplantation although pretransplant serum had negative results at both CDCXM and FCXM. Both patients had experienced more than one rejection episodes. CONCLUSIONS: Detection of DSA with more sensitive technique such as flow cytometry based method clearly displayed a beneficial effect for prediction of clinical outcome as a part of pretransplant compatibility test, and also as a posttransplant monitoring test to identify the de novo production of clinically significant DSA.

Factors associated with Endothelial Dysfunction in Hemodialysis Patients / 대한신장학회지

PURPOSE: Endothelial dysfunction is an event in the atherosclerotic process usually considered reversible at its early stage. Early detection, therefor, may improve the prognosis in the cardiovascular disease. The aim of this study was to investigate the vascular function in hemodialysis (HD) patients and to explore its relation to other various parameters with a specific emphasis on systemic inflammatory reaction (SIR), nutritional status and the presence of ischemic heart disease (IHD). METHODS: Flow-mediated endothelium-dependent vasodilatation (FMD) was measured, using Doppler sonogram, in 37 stable HD patients, 11 healthy people and 24 hypertensive controls. Nitroglycerine- induced endothelium-independent vasodilatation (EIV) and peak reaction time (PT) of each FMD and EIV were also measured. RESULTS: FMD in HD patients was decreased compared to healthy group whereas it was comparable in HD patients and hypertensive control. EIV in HD patients was significantly decreased compared to healthy and hypertensive controls. PT of each FMD and EIV was significantly delayed in HD patients. Each FMD and EIV showed a negative correlation with serum hsCRP level, but no significant correlations of FMD with other parameters were noted. Both FMD and EIV were further decreased in HD patients with IHD than non-IHD group. CONCLUSION: Our study confirmed a characteristic pattern of vascular dysfunction in HD patients: the impaired endothelial and smooth muscle function with a delayed reaction time. Importantly, SIR was one of the important factors determining vascular dysfunction in HD patients. Further studies will be necessary to define the causative role of SIR on endothelial dysfunction and the effect of inflammation- modulating therapy.

The Effect of FR167653, p38 Mitogen-Activated Protein Kinase (MAPK) Inhibitor, on the Expression of Slit Diaphragm-Associated Proteins in Experimental Diabetic Nephropathy / 대한신장학회지

PURPOSE: This study was undertaken to investigate the effect of a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor, FR167653, on urinary albumin excretion and on the expression of slit diaphragm-associated proteins in diabetic rats. METHODS: Thirty-two Sprague-Dawley rats were injected with diluent [control (C), N=16] or streptozotocin intraperitoneally (DM, N=16). Eight rats from each group were treated with 5 mg/kg/day FR 167653 (C+FR, DM+FR) for 6 weeks. At the time of sacrifice, 24-hour urinary albumin excretion was determined by ELISA. Glomerular nephrin, P-cadherin, and ZO-1 mRNA and protein expression were determined by real-time PCR and Western blot, respectively, with sieved glomeruli. RESULTS: Urinary albumin excretion was significantly higher in DM compared to C rats, and this increase in albuminuria was significantly inhibited by the administration of FR167653 in DM rats. Glomerular phospho-p38 MAPK protein expression was significantly increased in DM rats compared to C rats, and FR167653 treatment significantly attenuated the increase in phospho-p38 MAPK expression in DM glomeruli. Nephrin mRNA and protein expression were higher in 6-week DM compared to C glomeruli, and these increases were significantly abrogated with FR167653 treatment in DM rats. In contrast, FR167653 had no effects on the decrease in P-cadherin expression and the increase in ZO-1 expression observed in DM glomeruli. CONCLUSION: These findings suggest that FR167653, a p38 MAPK inhibitor, reduce the amount of albuminuria in early diabetic nephropathy, and this anti-proteinuric effect seems to be related with the change of glomerular nephrin expression.