Upregulation of NADH/NADPH oxidase 4 by angiotensin II induces podocyte apoptosis

Angiotensin II induces glomerular and podocyte injury via systemic and local vasoconstrictive or non-hemodynamic effects including oxidative stress. The release of reactive oxygen species (ROS) from podocytes may participate in the development of glomerular injury and proteinuria. We studied the role of oxidative stress in angiotensin II-induced podocyte apoptosis. Methods: Mouse podocytes were incubated in media containing various concentrations of angiotensin II at different incubation times and were transfected with NADH/NADPH oxidase 4 (Nox4) or angiotensin II type 1 receptor for 24 hours. The changes in intracellular and mitochondrial ROS production and podocyte apoptosis were measured according to the presence of angiotensin II. Results: Angiotensin II increased the generation of mitochondrial superoxide anions and ROS levels but suppressed superoxide dismutase activity in a dose- and time-dependent manner that was reversed by probucol, an antioxidant. Angiotensin II increased Nox4 protein and expression by a transcriptional mechanism that was also reversed by probucol. In addition, the suppression of Nox4 by small interfering RNA (siRNA) reduced the oxidative stress induced by angiotensin II. Angiotensin II treatment also upregulated AT1R protein. Furthermore, angiotensin II promoted podocyte apoptosis, which was reduced significantly by probucol and Nox4 siRNA and also recovered by angiotensin II type 1 receptor siRNA. Conclusion: Our findings suggest that angiotensin II increases the generation of mitochondrial superoxide anions and ROS levels via the upregulation of Nox4 and angiotensin II type 1 receptor. This can be prevented by Nox4 inhibition and/or antagonizing angiotensin II type 1 receptor as well as use of antioxidants.

The effects of indoxyl sulfate-induced endothelial microparticles on neointimal hyperplasia formation in an ex vivo model

PURPOSE: Neointimal hyperplasia (NH) is considered to be one of the main causes of vascular access occlusion in patients receiving hemodialysis. Endothelial injury and TGF-β-mediated proliferation of vascular smooth muscle cells (VSMCs) induce NH. Endothelial microparticles (EMPs) are also increased by endothelial injury. We aimed to investigate the effects of EMPs and TGF-β expression on VSMC proliferation and their contributions to NH formation in an ex vivo model. METHODS: EMPs were collected from the culture media of human umbilical vein endothelial cells treated with indoxyl sulfate (IS, 250 µg/mL) after ultracentrifugation at 100,000 × g. Porcine internal jugular veins were isolated and treated with EMPs (2 × 10⁶ /mL) or left untreated for 12 days and subsequently compared with TGF-β (10 ng/mL)-treated venous tissue. Intima-media thickness and NH area were assessed using a digital program. Masson's trichrome staining and immunohistochemistry (IHC) analysis for α-smooth muscle actin, phosphorylated Akt, ERK1/2, p38 mitogen-activated protein kinase (MAPK), and Smad3 were performed on each vein sample. RESULTS: NH and VSMC proliferation developed to a significantly greater degree in EMP-treated veins compared to controls, with similar patterns seen in TGF-β-stimulated samples. IHC analysis demonstrated that EMPs markedly increased phosphorylation of Akt, ERK1/2, p38 MAPK, and Smad3 in areas of venous NH formation. CONCLUSION: Our results showed that IS-induced EMPs provoked massive VSMC proliferation and NH formation via activation of the TGF-β signaling pathways. Further investigation is needed to elucidate the precise mechanism of EMP activity on vascular access stenosis in vivo.

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.

Urine synaptopodin excretion is an important marker of glomerular disease progression

BACKGROUND/AIMS: Podocytes play an important role in maintaining the glomerular filtration barrier and in formation of the slit diaphragm. Podocyte loss is associated with chronic kidney disease progression, but it is not clear whether urinary podocyte proteins in urine reflect the clinical extent of glomerular damage. We investigated the correlation between the amounts of urinary podocyte proteins and renal function and albuminuria. METHODS: The study enrolled 33 patients with diabetic kidney disease or glomerular disease and measured urinary podocytes proteins using Western blotting. Urinary podocyte proteins were measured according to the density of the bands on Western blotting. We measured serum creatinine and the spot urine albumin/creatinine ratio as markers of renal damage, and compared the correlation of urinary podocyte protein in the glomerular disease patients. RESULTS: The mean patient age was 49.3 ± 16.5 years, the mean serum creatinine level was 2.30 ± 1.76 mg/dL, and the mean albumin/creatinine ratio was 4.85 ± 3.52. Among the podocyte proteins, urine synaptopodin showed strong correlation with serum creatinine by multivariate regression analysis (p < 0.001) and showed linear correlation (r = 0.429, p < 0.01). Urine podocyte proteins were increased in patients with diabetes, and synaptopodin showed the greatest significant difference (7.68 ± 5.61 vs. 2.56 ± 3.11, p < 0.001), but this might be associated with renal impairment. The urine albumin excretion did not differ between the diabetics and non-diabetics (p = 0.73). CONCLUSIONS: Urine synaptopodin is associated with serum creatinine elevation in the patients with glomerulonephritis including diabetic kidney disease regardless of urine albumin excretion. We suggest that the urine synaptopodin level can predict glomerular damage independently of the urine albumin excretion.

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.

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.

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.

Renal Expression of an Ammonia Transporter in Rats with a Unilateral Ureteral Obstruction / 대한내과학회지

BACKGROUND/AIMS: Urinary tract obstruction induces a form of renal tubular acidosis with a urinary acidification defect caused by decreasing net acid excretion, which is predominantly due to a decrease in urinary ammonia excretion. The present study examined whether this decrease is associated with changes in the renal expression of an ammonia transporter family member, Rh C glycoprotein (Rhcg), in rats with a unilateral ureteral obstruction. METHODS: Male Sprague-Dawley rats underwent a 24-h unilateral ureteral obstruction. Rhcg expression was then evaluated by immunoblotting and immunohistochemistry. Cell height, total cellular expression, expression in the apical 25% of the cell, and % of total expression in the apical region were quantified by immunohistochemistry with quantitative morphometric analysis. RESULTS: After 24 h of unilateral ureteral obstruction, the serum bicarbonate level and total urinary ammonia excretion were decreased. Both light microscopy and immunohistochemistry with quantitative morphometric analysis demonstrated that the total intensity of Rhcg expression was decreased in the obstructed kidneys, whereas Rhcg expression did not change in the cortical collecting duct (CCD) and outer medullary collecting duct (OMCD) of nonobstructed kidneys in rats with a 24-h unilateral ureteral obstruction. CONCLUSIONS: The rats with a unilateral ureteral obstruction showed decreased urinary ammonia excretion associated with decreased Rhcg expression in the CCD and OMCD. These changes suggest that the ammonia transporter Rhcg mediates a urinary acidification defect associated with unilateral ureteral obstruction.

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.

The Effects of Carnitine Supplementation in Hemodialysis Patients / 이화의대지

OBJECTIVES: Patients receiving hemodialysis have been shown to be carnitine deficient due to many causes. Tissues, especially the skeletal muscle and myocardium, require carnitine for the production of energy. This study was performed to find out the effects of L-carnitine supplementation on muscular symptoms and cardiac functions in dialysis patients. METHODS: Among 72 hemodialysis patients, 40 patients who showed decreased free carnitine levels were selected to receive L-carnitine intravenously after each hemodialysis session for 6 months. Before and after supplementation, echocardiography, various neurologic examinations and questionnaires were obtained. RESULTS: After carnitine treatment for 6 months (1~1.5 g per every hemodialysis session), the blood level of carnitine was increased more than 10 times (19.04+/-7.12 micromol/L vs. 267.24+/-69.94 micromol/L, P<0.001). The left ventricular ejection fraction was improved in the patients who have less than 60% of ejection fraction (56.45+/-2.53% vs. 60.44+/-6.29%, P=0.03) after carnitine treatment. The neurological symptom score and isometric muscle power (pinch power) were improved, but the total neuropathy score, activities of daily living scale and grip power were not changed after carnitine supplementation on dialysis patients. CONCLUSION: Regular L-carnitine supplementation on hemodialysis patients can improve their left ventricular ejection fraction and some parts of functionality.

Buttonhole Technique in Hemodialysis / 대한내과학회지

Recently, dialysis population with arteriovenous fistula may have some problems about the cannulation due to aged, incompetent vessels. Thus alternative needling method, buttonhole technique has been suggested for the complicated cannulation route. In spite of various benefits, this technique is difficult to apply in Korean hemodialysis unit because it requires much time to form the buttonhole track or tunnel. Meanwhile, Choi et al. reported the superiority of buttonhole technique using the polycarbonate peg, Biohole(TM). Here, we review the buttonhole technique in hemodialysis including new buttonhole technique using the Biohole(TM).

Interleukin-6 -634 C/G and -174 G/C Polymorphisms in Korean Patients Undergoing Hemodialysis

BACKGROUND/AIMS: Chronic inflammatory status is a possible risk factor for vascular access dysfunction in hemodialysis (HD) patients, but susceptibility differences appear among individuals. Interleukin (IL)-6 is a well-known inflammatory cytokine with various polymorphisms. We examined whether IL-6 polymorphisms are associated with vascular access dysfunction in HD patients. METHODS: A total of 80 HD patients (including 42 diabetic patients) were enrolled. Polymorphisms in the IL-6 gene promoter (-634 C/G and -174 G/C) were studied using restriction length polymorphism polymerase chain reaction analysis. Vascular access patency was compared between the patient groups with respect to IL-6 polymorphisms. An additional 89 healthy individuals were enrolled in the control group. Plasma IL-6 levels were de termined by enzyme-linked immunosorbent assay. RESULTS: The GG genotype and G allele at position -634 in the IL-6 promoter were more frequently observed in HD patients than in controls. Furthermore, the distribution of the -634 polymorphism differed according to vascular access patency in non-diabetic HD patients. However, the G allele was not a significant risk factor for early access failure. No significant association appeared between the IL-6 -634 C/G polymorphism and plasma IL-6 levels. The C allele of the IL-6 -174 G/C polymorphism was not detected in our study population. CONCLUSIONS: The IL-6 -634 G allele appears with greater frequently in patients with end-stage renal disease and may be associated with vascular access dysfunction in non-diabetic HD patients.

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.

Renal Expression of Ammonia Transporters in Rats with Amiloride-Induced Renal Tubular Acidosis / 대한내과학회지

BACKGROUND/AIMS: Renal tubular acidosis (RTA) decreases the net acid excretion, predominantly due to a decrease in urinary ammonia excretion. This study examined whether this decrement is associated with changes in the renal expression of the ammonia transporter family members, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg), in rats with amiloride-induced RTA. METHODS: Male Sprague-Dawley rats were treated intraperitoneally with amiloride (3 mg/kg/day) for 6 days. Rhbg and Rhcg expression was evaluated by immunoblotting and immunohistochemistry. Cell height, total cellular expression, expression in the apical 25% of the cell, and apical expression as a percentage of total expression were quantified using immunohistochemistry with quantitative morphometric analysis. RESULTS: After amiloride treatment for 6 days, the serum bicarbonate level was decreased, and serum potassium was increased. The total urinary ammonia excretion and potassium excretion were decreased. The total Rhbg and Rhcg protein expression levels were not changed in the cortex or outer medulla of the kidney. Light microscopy and immunohistochemistry with quantitative morphometric analysis demonstrated that total Rhcg expression was decreased in the cortical collecting duct (CCD) and outer medullary collecting duct (OMCD) in amiloride-induced RTA, whereas Rhbg immunoreactivity was unchanged. CONCLUSIONS: Rats with amiloride-induced RTA have decreased urinary ammonia excretion associated with decreased Rhcg expression in the CCD and OMCD, suggesting that the ammonia transporter Rhcg plays an important role in the pathogenesis of amiloride-induced RTA.

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.