Search

Hyperglycemia-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGEs) play major roles in diabetic nephropathy progression. In previous study, both glucagon-like peptide-1 (GLP-1) and peroxisome proliferator-activated receptors delta (PPARδ) agonists were shown to have anti-inflammatory effect on AGE-treated rat mesangial cells (RMCs). The interaction among PPARδ agonists, GLP-1, and AGE-RAGE axis is, however, still unclear.In this study, the individual and synergic effect of PPARδ agonist (L-165 041) and siRNA of GLP-1 receptor (GLP-1R) on the expression of GLP-1, GLP-1R, RAGE, and cell viability in AGE-treated RMCs were investigated.L-165 041 enhanced GLP-1R mRNA and protein expression only in the presence of AGE. The expression of RAGE mRNA and protein was enhanced by AGE, attenuated by L-165 041, and siRNA of GLP-1R reversed L-165 041-induced inhibition. Cell viability was also inhibited by AGE. L-165 041 attenuated AGE-induced inhibition and siRNA GLP-1R diminished L-165 041 effect.PPARδ agonists increase GLP-1R expression on RMC in the presence of AGE. PPARδ agonists also attenuate AGE-induced upregulated RAGE expression and downregulated cell viability. The effect of PPARδ agonists needs the cooperation of GLP-1R activation.

Background In patients with heart failure, interleukin-18 (IL-18) levels increase in the circulatory system and injured myocardial tissue. Serotonin (5-hydroxytryptamine) receptors subtype 2B (HTR2B) play an essential role in cardiac function and development, and their overexpression in rats leads to myocardial hypertrophy. Epigallocatechin gallate (EGCG) is cardioprotective in myocardial ischemia–reperfusion injury in rats and can prevent pressure overload-mediated cardiac hypertrophy in vivo. Mice deficient in peroxisome proliferator-activated receptor delta (PPARδ) can have cardiac dysfunction, myocardial hypertrophy, and heart failure. Matrix metalloproteinases (MMPs) are possibly involved in cardiac remodeling. However, the relationship between IL-18 signaling, cardiac hypertrophy, and the molecular mechanisms involved remain to be fully elucidated. Objectives To elucidate the relationship between HTR2B and IL-18-induced myocardial hypertrophy and examine the antihypertrophic effects of EGCG and PPARδ. Methods We induced H9c2 cardiomyoblast hypertrophy with IL-18 in vitro and investigated the downstream signaling by real-time polymerase chain reaction (PCR) and western blotting. Hypertrophy was assessed by flow cytometry. We determined the effects of EGCG and PPARδ on IL-18-induced hypertrophic signaling via HTR2B-dependent mechanisms. Results IL-18-induced H9c2 hypertrophy upregulated brain natriuretic peptide (BNP) protein and mRNA expression by inducing the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and the hypertrophy was attenuated by pretreatment with EGCG (20 μM) and L-165,041 (2 μM), a PPARδ agonist. IL-18 upregulated the expression of HTR2B, which was inhibited by pretreatment with EGCG and L-165,041. SB215505 (0.1 μM), a HTR2B antagonist and siRNA for HTR2B, attenuated H9c2 hypertrophy significantly. Inhibition of HTR2B also downregulated the expression of MMP-3 and MMP-9. Conclusions IL-18 and HTR2B play critical roles in cardiomyoblast hypertrophy. EGCG and L-165,041 inhibit the expression of HTR2B and augment remodeling of H9c2 cardiomyoblasts, possibly mediated by MMP-3 and MMP-9.

The number of diagnosed diabetic patients is increasing worldwide. Many people with diabetes develop wounds that are slow to, or never, heal, which can lead to serious health issues. Diabetes causes long-term excessive blood glucose buildup in human body, which leads to an over-reactive inflammatory response and excessive oxidative stress. As a result, varied wound healing effects were observed according to different circumstances and stage of healing. We used two diabetic wound animal models to analyze the wound healing effect of

Acute kidney injury (AKI) is one of the major complications with increased oxidative stress and inflammation in diabetic patients. Hyperglycemia stimulates the formation of advanced glycation end products (AGEs). However, hyperglycemia directly triggers the interaction between AGEs and transmembrane AGEs receptors (RAGE), which enhances oxidative stress and increases the production of inflammatory substances. Therefore, diabetes plays a pivotal role in kidney injury. Hydralazine, a vasodilator and antihypertensive drug, was found to have the ability to reduce ROS, oxidative stress, and inflammation. We applied Hydralazine co-culture with AGEs in rat mesangial cells (RMC) and to renal ischemia/reperfusion(I/R) injury models in streptozotocin-induced diabetic rats. Hydralazine significantly decreased AGEs-induced RAGE, iNOS, and COX-2 expressions in RMC. Compared to the diabetic with AKI group, hydralazine decreased inflammation-related protein, and JAK2, STAT3 signaling in rat kidney tissue. Our studies indicate that Hydralazine has the potential to become a beneficial drug in the treatment of diabetic acute kidney injury.

BACKGROUND Rapid shifting between extracellular and intracellular phosphorus can occur during dialysis sessions, which can cause aberrant intracellular signaling in long-term hemodialysis (LTHD) patients. However, the effect of these intra-dialysis fluctuations of phosphorus on clinical outcomes has not been examined. Therefore, we investigated the relationship between intradialysis serum phosphorus reduction ratio (IDSPRR) and mortality in LTHD patients. MATERIAL AND METHODS This was a retrospective, observational cohort study to assess the predictive power of IDSPRR (>0.63 vs. ≤0.63) on mortality in a total of 805 LTHD patients. All these fatal events were analyzed using the Cox proportional hazards regression model. RESULTS After multivariable analysis, baseline IDSPRR higher than 0.63 was significantly predictive of all-cause mortality (hazard ratio [HR]: 1.58; 95% confidence interval [CI]: 1.10-2.26), but not for cardiovascular (CV) mortality (HR: 1.41; 95% CI: 0.91-2.18). However, when time-varied IDSPRRs were applied, a value greater than 0.63 was not only significantly predictive of all-cause mortality (HR: 1.74, 95% CI: 1.16-2.63), but also CV mortality (HR: 2.04, 95% CI: 1.23-3.40). CONCLUSIONS High IDSPRR (>0.63) is independently associated with increased all-cause and CV mortality, which shows the negative effect of rapid intracellular phosphorus-shifting on LTHD patients.

Despite reported evidence on the relationship between higher serum aluminum levels and poor outcomes in patients on chronic hemodialysis (CHD), the acceptable cutoff value of serum aluminum for mortality remains unclear. A retrospective observational cohort study with 636 Taiwanese patients on CHD was conducted to investigate the impact of serum aluminum levels on mortality. The predictors were bivariate serum aluminum level (

Patient: Female, 38 Final Diagnosis: Primary hyperaldosteronism Symptoms: Paralysis Medication: — Clinical Procedure: — Specialty: Nephrology Objective: Challenging differential diagnosis Background: Thyrotoxic periodic paralysis (TPP) is commonly observed in patients with acute paralysis and hyperthyroidism. However, there is a possibility of secondary causes of hypokalemia in such a setting. Case Report: Herein, we present the case of a 38-year-old woman with untreated hypertension and hyperthyroidism. She presented with muscle weakness, nausea, vomiting, and diarrhea since one week. The initial diagnosis was TPP. However, biochemistry tests showed hypokalemia with metabolic alkalosis and renal potassium wasting. Moreover, a suppressed plasma renin level and a high plasma aldosterone level were noted, which was suggestive of primary aldosteronism. Abdominal computed tomography confirmed this diagnosis. Conclusions: Therefore, it is imperative to consider other causes of hypokalemia (apart from TPP) in a patient with hyper-thyroidism but with renal potassium wasting and metabolic alkalosis. This can help avoid delay in diagnosis of the underlying disease.

Background Myasthenia gravis (MG) is the most common disorder of neuromuscular transmission, and it is typified by fluctuating degrees and variable combinations of weakness in the ocular, bulbar, limb, and respiratory muscles. Under rare circumstances, MG can be accompanied by Addison’s disease. Case presentation Here, we reported the case of a 57-year-old Chinese woman with MG. She experienced progressive muscle weakness for 1 week. MG with acute exacerbation was initially suspected. However, further biochemistry tests found mild hyperkalemia (5.6 mEq/L) and a lower renal potassium excretion rate. Consequently, low aldosterone action was highly suspected. Further findings included a suppressed cortisol level, a higher adrenocorticotropic hormone concentration, and 21-hydroxylase antibody positivity, supporting a diagnosis of primary adrenal insufficiency due to autoimmune adrenalitis. Conclusion We successfully demonstrated that adrenal insufficiency could be diagnosed, due to the presence of hyperkalemia. This case suggested a need for clinicians to consider the possible coincidence of adrenal insufficiency in a patient with MG and hyperkalemia. Early hormone supplementation should be begun.

Background: The endothelial progenitor cells (EPCs) dysfunction is a critical event in the initiation of atherosclerotic plaque development and the level of circulating EPCs can be considered a biomarker of cardiovascular events. The level and functional change in EPCs has been investigated in hemodialysis patients, but the effect of absolute number of EPCs on risk of death has not yet been explored. We hypothesized that the number of EPCs predicted death from cardiovascular and all-cause mortality in hemodialysis patients. Methods: We evaluate the association between endothelial progenitor cells and clinical outcome in 154 patients on maintenance hemodialysis. The blood sample was drawn at the time of patient enrollment and EPCs were identified by flow cytometry using triple staining for CD34/CD133/KDR. Results: The median duration of follow-up was 4.19 years. There were 79 (51.3%) deaths during the follow-up period, 41 of whom died due to a confirmed cardiovascular cause. The cumulative survival was greater in the high-EPC group than the low-EPC group for all-cause and cardiovascular mortality. Decreased EPCs levels were associated with a significant increase in the risk of cardiovascular and all-cause mortality after adjusting for age, gender, current smokers, diabetes mellitus, and hypertension. Conclusions: The level of circulating EPCs independently predicts the clinical outcome in patients on maintenance hemodialysis. Thus, the EPCs levels may be a useful predictive tool for evaluating the risk of death in maintenance hemodialysis patients.

Patients with uremia are often immunocompromised and uremia patients undergoing maintenance dialysis are often vulnerable to uncommon infections. We report a 40-year-old man who was undergoing maintenance hemodialysis and was initially diagnosed with monomicrobal necrotizing fasciitis of the lower limbs, based on blood and pus cultures that yielded Escherichia coli. His condition improved after surgical debridement and antibiotic therapy. However, he eventually died of intracranial hemorrhage related to septic emboli. Concurrent infective endocarditis was diagnosed based on an echocardiogram that indicated vegetation in the left ventricular region. Escherichia coli-related necrotizing fasciitis and infective endocarditis is rarely seen in clinical practice. There should be a high index of suspicion for multiple infections when a hemodialysis patient presents with an uncommon infection.

Background Hyperglycemia-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGE) production play major roles in progression of diabetic nephropathy. Anti-RAGE effect of peroxisome proliferator-activated receptor-delta (PPARδ) agonists was shown in previous studies. PPARδ agonists also stimulate glucagon-like peptide-1 (GLP-1) secretion from human intestinal cells. Methods In this study, the individual and synergic anti-inflammatory effects of GLP-1 receptor (exendin-4) and PPARδ (L-165,041) agonists in AGE-treated rat mesangial cells (RMC) were investigated. Results The results showed both exendin-4 and L-165,041 significantly attenuated AGE-induced IL-6 and TNF-α production, RAGE expression, and cell death in RMC. Similar anti-inflammatory potency was seen between 0.3 nM exendin-4 and 1 μM L-165,041. Synergic effect of exendin-4 and L-165,041 was shown in inhibiting cytokines production, but not in inhibiting RAGE expression or cell death. Conclusions These results suggest that both GLP-1 receptor and PPARδ agonists have anti-inflammatory effect on AGE-treated rat mesangial cells.

ObjectivesTo investigate the impact of vascular access flow (Qa) on vascular and all-cause mortality in chronic haemodialysis (HD) patients.DesignObservational cohort study.SettingSingle centre.ParticipantsAdult chronic HD patients at the HD unit of Shin Kong Wu Ho-Su Memorial Hospital between 1 January 2003 and 31 December 2003 were recruited. Patients were excluded if they had arteriovenous fistula or arteriovenous graft failure within 3 months before the date of Qa measurement, were aged InterventionsThe selected patients were evaluated with Qa and cardiac index (CI). They were divided into four groups according to three Qa cut-off points (500, 1000 and 1500 mL/min).Primary and secondary outcome measuresShort-term and long-term vascular (cardiovascular or cerebrovascular) and all-cause mortality.ResultsQa was positively correlated with CI (r=0.48, pConclusionsQa is moderately correlated with cardiac function, and a Qa level of

Wound healing is one of the major complications of diabetes, and problems with wound healing in diabetics often lead to amputation and even death. AMP-activated protein kinase (AMPK) is a protein involved in intracellular metabolism. Activated AMPK can reduce visceral fat and cholesterol synthesis and even inhibit hepatic gluconeogenesis. Activation of AMPK has been widely used in the treatment of type II diabetes. We applied an AMPK activator (Adenine) to human fibroblasts and to the wounds of streptozotocin-induced diabetic mice. We applied Adenine ointment to the wounds on 7 consecutive days and observed the healing status as well as activation of AMPK and angiogenic factors. Based on the appearance of the wounds, the results showed that after 7 days of treatment the wound area was smaller in the Adenine-treated group relative to the control group. The results for tissue protein expression showed that, compared to the control group, angiogenic related protein, PPARδ were increased and receptor for advanced glycation endproducts (RAGE) was decreased in the Adenine-treated group. Our studies indicate that Adenine has the potential to become a useful drug in the treatment of diabetic wound healing.

The cardiothoracic ratio (CTR) and serum aluminum levels are both associated with mortality in hemodialysis patients. However, limited data regarding the association between serum aluminum levels and the CTR have been published to date. Therefore, we aimed to elucidate this association in patients on chronic hemodialysis (CHD). We investigated the association between the serum aluminum level and the CTR in CHD in a retrospective cross-sectional study of 547 Taiwanese patients on CHD. The mean age of patients was 62.5±13.2 years, with a mean hemodialysis time of 7.1±5.2 years. Among the patients, 36.9% were diabetic and 47.9% were male. After natural logarithmic transformation (ln(aluminum)), the serum aluminum level exhibited an independent and linear relationship with the CTR (β: 1.40, 95% confidence interval (CI), 0.6-2.2). A high serum aluminum level (≥6 ng/dL) was significantly associated with a CTR >0.5 in the crude analysis (odds ratio (OR): 2.15, 95% CI, 1.52-3.04) and remained significant after multivariable adjustment (OR: 2.45, 95% CI, 1.63-3.67). Moreover, the ln(aluminum) value was significantly associated with a CTR >0.5 (OR: 1.71, 95%CI, 1.28-2.29) in multivariable analysis, indicating a dose effect of aluminum on cardiomegaly. In conclusion, the serum aluminum level was independently associated with cardiac remodeling (elevated CTR) in patients on CHD.

The ankle-brachial index (ABI) is associated with peripheral vascular atherosclerosis, adverse cardiovascular outcomes, and all-cause mortality. However, there were limited data available on studying the effect of interleg ABI difference.We investigated the association of the interleg ABI difference with overall and cardiovascular mortality in chronic hemodialysis in a retrospective observational cohort of 369 Taiwanese patients undergoing chronic hemodialysis.An interleg ABI difference of ≥0.15 in hemodialysis patients had significant predictive power for all-cause and cardiovascular mortality in crude analysis. The hazard ratio (HR) for all-cause mortality was 3.00 [95% confidence interval (CI), 1.91-4.71]; the HR for cardiovascular mortality was 3.13 (95% CI, 1.82-5.38). After adjustment for confounding variables, this difference continued to have significant predictive power for all-cause mortality but lost its predictive power for fatal cardiac outcome. ABI0.9 and high brachial-ankle pulse wave velocity were independently associated with an interleg ABI difference of ≥0.15 in hemodialysis patients. Moreover, in the subgroup analysis, we found that this difference was an independent factor for overall and cardiovascular mortality, particularly in elder patients, female patients, or those with ABI0.9.Detection of an interleg ABI difference of ≥0.15 was an independent risk factor for overall mortality in hemodialysis patients but it may affect cardiovascular mortality through the effect of peripheral vascular disease.

Diabetic nephropathy is the leading cause of end-stage renal disease in the most developed countries of the world. Hyperglycemia-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGE) production, pro-inflammatory cytokine secretion, and oxidative stress activation play major roles in kidney cell injury and apoptosis. Peroxisome proliferator-activated receptor-gamma (PPARγ) agonists are used clinically as insulin sensitizers. This study evaluated the renoprotective effect of PPARγ (troglitazone) and PPARδ (L-165,041) agonists on human embryonic kidney 293 (HEK) and mesangial cells. Troglitazone (10 μM) and L-165,041 (1 μM) significantly inhibited high glucose (25mM)-induced interleukin-6 and TNF-α production, RAGE expression and NF-κB translocation in HEK cells. Furthermore, Troglitazone (10 μM) and L-165,041(1 μM) significantly increased SOD expression and attenuated apoptosis in HEK and mesangial cells. The inhibitory effect between 1 μM L-165,041 and 10 μM troglitazone showed no difference. Furthermore L-165,041 and troglitazone together did not increase the effects. These results provide important information for future application of PPAR agonists in diabetic nephropathy treatment.

The cardiothoracic ratio (CTR) and peripheral arterial occlusive disease (PAOD) are related to mortality in hemodialysis patients. However, data on the association between PAOD and CTR are limited. In this study, we aim to elucidate this relationship in patients on chronic hemodialysis. Using a retrospective cross-sectional study of 622 Taiwanese patients, we investigated the association of PAOD and CTR. PAOD was significantly associated with CTR in the crude analysis. The odds ratio (OR) for CTR >0.5 was 1.77 [95% confidence interval (CI), 1.32–2.37], and the odds ratio for CTR >0.6 was 2.18 [95% CI, 1.44–3.30]. After adjusting for confounding variables, this difference continued to exhibit significant predictive power for CTR >0.6 (OR, 1.88; 95% CI, 1.14–3.11), but the predictive power for CTR >0.5 was attenuated (OR, 1.41; 95% CI, 0.98–2.03). In the subgroup analysis, PAOD was an independent factor for CTR >0.6, particularly in elderly and female patients or patients with hemoglobin >10 mg/dl and with no history of cardiovascular disease. In this research, we showed that the detection of PAOD was independently associated with CTR >0.6 in patients on chronic hemodialysis.

Topical applications of antioxidant agents in cutaneous wounds have attracted much attention. Gold nanoparticles (AuNPs), epigallocatechin gallate (EGCG), and α-lipoic acid (ALA) were shown to have antioxidative effects and could be helpful in wound healing. Their effects in Hs68 and HaCaT cell proliferation and in mouse cutaneous wound healing were studied. Both the mixture of EGCG + ALA (EA) and AuNPs + EGCG + ALA (AuEA) significantly increased Hs68 and HaCaT proliferation and migration. Topical AuEA application accelerated wound healing on mouse skin. Immunoblotting of wound tissue showed significant increase of vascular endothelial cell growth factor and angiopoietin-1 protein expression, but no change of angiopoietin-2 or CD31 after 7 days. After AuEA treatment, CD68 protein expression decreased and Cu/Zn superoxide dismutase increased significantly in the wound area. In conclusion, AuEA significantly accelerated mouse cutaneous wound healing through anti-inflammatory and antioxidation effects. This study may support future studies using other antioxidant agents in the treatment of cutaneous wounds. From the Clinical Editor In this study, topically applied gold nanoparticles with epigallocatechin gallate and alpha-lipoic acid were studied regarding their effects in wound healing in cell cultures. Significant acceleration was demonstrated in wound healing in a murine model.

Iliopsoas abscess is a rare complication in hemodialysis patients that is mainly due to adjacent catheterization, local acupuncture, discitis, and bacteremia. Herein, we report a 47-year-old woman undergoing regular hemodialysis via a catheter in the internal jugular vein who presented with low back pain and dyspnea. A heart murmur suggested the presence of catheter-related endocarditis, and this was confirmed by an echocardiogram and a blood culture of methicillin-resistant Staphylococcus aureus. A computed tomography indicated a pulmonary embolism and an incidental finding of iliopsoas abscess. Following surgical intervention and intravenous daptomycin, the patient experienced full recovery and a return to usual activities. This case indicates that an iliopsoas abscess can be related to a jugular vein catheter, which is apparently facilitated by infective endocarditis. The possibility of iliopsoas abscess should be considered when a hemodialysis patient presents with severe low back pain, even when there is no history of adjacent mechanical intervention.

Background Inflammation associated with endothelial cell dysfunction is a key step of atherogenesis. C-reactive protein (CRP), used to serve as a nonspecific clinical inflammation marker, has now emerged as a new marker for cardiovascular diseases. Recently, PPARδ has revealed benefits for dealing with inflammation. The relationship between CRP-induced inflammation and PPARδ agonist remains unclear. Methods Human umbilical vein endothelial cells (HUVECs) were separated into the following groups: 25 μg CRP alone for 15 hours; CRP-treated with 1 μM PPARδ(L-165041) or 10 μM PPARγ(troglitazone) agonists, and untreated HUVECs. This research focused on the CRP underlying signaling pathways and the effects of PPAR agonists on monocyte attachment to endothelial cells. Results Levels of interleukin-6 (IL-6) and IL-8 increased by CRP were both significantly attenuated by pretreatment with PPARδ or PPARγ agonists, but the needed dose of PPARδ to reach the same effect was less than PPARγ agonist. After incubation with CRP, immunoblotting showed a significant increase in NF-κB activation and CD32 receptor. These changes were associated with a significant increase of MCP-1 and VCAM-1 expression. PPARδ treatment not only decreased these pro-inflammatory effects in HUVECs but also significantly attenuated monocyte adhesion to endothelial cells in less dosage than PPARγ. Conclusions The results suggest that PPARδ attenuated CRP-induced pro-inflammatory effects may through CD32 and NF-κB pathway. PPARδ may serve as a more potent therapeutic target than PPARγ in atherosclerosis or inflammatory therapy.

Background Diabetic nephropathy has attracted many researchers' attention. Because of the emerging evidence about the effects of advanced glycation end products (AGEs) and receptor of AGE (RAGE) on the progression of diabetic nephropathy, a number of different therapies to inhibit AGE or RAGE are under investigation. The purpose of the present study was to examine whether peroxisome proliferator-activated receptor δ (PPARδ) agonist (L-165041) or epigallocatechin gallate (EGCG) alters AGE-induced pro-inflammatory gene expression and apoptosis in human embryonic kidney cells (HEK293) and human mesangial cells (HMCs). Methods The HEK cells and HMC were separated into the following groups: 100 µg/mL AGE alone for 18 h; AGE treated with 1 µM L-165041 or 10 µM EGCG, and untreated cells. Inflammatory cytokines, nuclear factor-κB pathway, RAGE expression, superoxide dismutase and cell apoptosis were determined. Results AGE significantly increased tumour necrosis factor-α (TNF-α), a major pro-inflammatory cytokine. The mRNA and protein expression of RAGE were up-regulated. These effects were significantly attenuated by pre-treatment with L-165041 or EGCG. AGE-induced nuclear factor-κB pathway activation and both cells apoptosis were also inhibited by L-165041 or EGCG. Furthermore, both L-165041 and EGCG increased superoxide dismutase levels in AGE-treated HEK cells and HMC. Conclusions This study demonstrated that PPARδ agonist and EGCG decreased the AGE-induced kidney cell inflammation and apoptosis. This study provides important insights into the molecular mechanisms of EGCG and PPARδ agonist in attenuation of kidney cell inflammation and may serve as a therapeutic modality to treat patients with diabetic nephropathy. Copyright © 2010 John Wiley & Sons, Ltd.

Multidisciplinary predialysis education and team care (MDC) may slow the decline in renal function in patients with chronic kidney disease (CKD). However, associations between unexpected return during MDC and progression of renal dysfunction have not been characterized in patients with CKD. Our study aimed to determine the association between exacerbation of renal dysfunction and the frequency of unexpected return during follow-up. A total of 437 patients with CKD receiving multidisciplinary care between January 2009 and June 2013 at the Shin-Kong Wu Ho-Su Memorial Hospital were included in this retrospective observational cohort study, and multiple imputations were performed for missing data. The predictor was the frequency of unexpected return for follow-up during the first year after entering MDC. Main outcome was monthly declines in estimated glomerular filtration rates (eGFR). Moreover, the demographic data, comorbidities, history of medication, and routine laboratory data for patients with CKD were collected. Among all patients, 59.7% were male, the mean age at initiation of MDC was 69.4 ± 13.2 years, and the duration of follow-up was 21.4 ± 3.3 months. The subjects were divided into 2 groups according to frequencies of follow-up (≤4 and > 4 visits) during the 1st year of MDC. The patients with CKD were regularly followed up every 3 months as a part of MDC in our hospital, and patients who returned for more than 4 follow-up visits were included in the unexpected return group. In crude regression analyses, unexpected return was significantly associated with higher monthly declines of eGFR (β = 0.092, 95% confidence interval, 0.014–0.170). This association remained after adjustments for multiple variables, and subgroup analyses of unexpected return showed that male gender, older age, CKD stage 1 to 3, hypertension, history of coronary artery disease, and use of renin–angiotensin system blockade were significantly associated with declines in renal function. In conclusion, unexpected return for follow-up during the 1st year of MDC was significantly associated with the deterioration of renal function.

Patients with uremia are often immunocompromised and uremia patients undergoing maintenance dialysis are often vulnerable to uncommon infections. We report a 40-year-old man who was undergoing maintenance hemodialysis and was initially diagnosed with monomicrobal necrotizing fasciitis of the lower limbs, based on blood and pus cultures that yielded Escherichia coli. His condition improved after surgical debridement and antibiotic therapy. However, he eventually died of intracranial hemorrhage related to septic emboli. Concurrent infective endocarditis was diagnosed based on an echocardiogram that indicated vegetation in the left ventricular region. Escherichia coli-related necrotizing fasciitis and infective endocarditis is rarely seen in clinical practice. There should be a high index of suspicion for multiple infections when a hemodialysis patient presents with an uncommon infection.

Background The ankle—brachial blood pressure (BP) index (ABI) not only indicates the presence of peripheral artery occlusive disease (PAOD) but predicts mortality in patients undergoing hemodialysis (HD). However, whether the site of PAOD can provide additional contribution to predicting mortality have not been investigated yet. Our primary objective was to determine the associations between the site of PAOD and all-cause and cardiovascular mortality in chronic HD (CHD) patients. Methods A retrospective cohort study was conducted to evaluate 444 Taiwanese CHD patients between December 2006 and June 2013. The site of PAOD together with other explanatory variables such as demographic data, body mass index, a history of cardiovascular diseases, HD vintage, biochemical data, and cardiothoracic ratio (CTR) were assessed by the Cox proportional hazards regression model. Results The frequency of PAOD was 14.6% in both legs, 4.9% in the right side only, and 5.1% in the left side only. During the study period, 127 all-cause and 93 cardiovascular deaths occurred. PAOD site was found to have significant predictive power for all-cause mortality with the order of 3.04 (95% CI: 1.56–5.90) hazard ratio on the right side, 2.48 (95% CI: 1.27–4.82) on the left side, and 4.11 (95% CI: 2.76–6.13) on both sides. The corresponding figures for cardiovascular mortality were 3.81 (95% CI: 1.87–7.76) on the right side, 2.76 (95% CI: 1.30–5.82) on the left side, and 3.95 (95% CI: 2.45–6.36) on both sides. After adjustment for other explanatory variables, only right-sided PAOD still remained to have significant predictive power for all-cause and cardiovascular mortality and bilateral PAOD kept the significant association with all-cause mortality. Conclusions The site of PAOD revealed various predictive powers for all-cause and cardiovascular mortality in CHD patients and only right-sided PAOD remained an independent predictor for both types of mortality making allowance for relevant confounding factors.

Modulation of Tie2 receptor activity by angiopoietin ligands is crucial for angiogenesis, blood vessel maturation, and vascular endothelium integrity. The role of the angiopoietin (Ang) and Tie system in myocardial infarction is not well understood. To investigate the participation of the Ang/Tie in myocardial infarction, adult Sprague-Dawley rats with ligation of the left anterior descending coronary artery to induce myocardial infarction were studied. Ang1, Ang2, Tie1, and Tie2 were measured immediately after ligation of the coronary artery, and at 6 h, 1 and 3 days, and 1, 2, 3 and 4 weeks after ligation by Northern blotting, Western blotting, and immunohistochemical staining. Ang2 mRNA significantly increased from 2 weeks (2.1-fold) to 4 weeks (2.9-fold) after the infarction in the left ventricular free wall. Tie2 mRNA increased significantly from 1 week (2.1-fold) to 4 weeks (3.8-fold) after the infarction. Ang2 protein also significantly increased from 3 days (1.9-fold) to 4 weeks (3-fold) after the infarction in the left ventricular free wall. Tie2 protein increased 2.4-fold at 3 weeks and 2.8-fold at 4 weeks after the infarction. Neither Ang1 nor Tie1 mRNA or protein showed any significant change at any time point after the infarction. The ratio of Ang2/Ang1 mRNA and protein in the study group was higher than that in the control group. Ang2 and Tie2 expression in nonischemic myocardium showed no significant change. Immunohistochemical study also showed increased immunoreactivity of Ang2 and Tie2 at the infarct border. In conclusion, Ang2 and Tie2 expressions significantly increased both spatial and temporal patterns after myocardial infarction in the rat ventricular myocardium, while Ang1 and Tie1 receptor expression did not.

Iliopsoas abscess is a rare complication in hemodialysis patients that is mainly due to adjacent catheterization, local acupuncture, discitis, and bacteremia. Herein, we report a 47-year-old woman undergoing regular hemodialysis via a catheter in the internal jugular vein who presented with low back pain and dyspnea. A heart murmur suggested the presence of catheter-related endocarditis, and this was confirmed by an echocardiogram and a blood culture of methicillin-resistant Staphylococcus aureus. A computed tomography indicated a pulmonary embolism and an incidental finding of iliopsoas abscess. Following surgical intervention and intravenous daptomycin, the patient experienced full recovery and a return to usual activities. This case indicates that an iliopsoas abscess can be related to a jugular vein catheter, which is apparently facilitated by infective endocarditis. The possibility of iliopsoas abscess should be considered when a hemodialysis patient presents with severe low back pain, even when there is no history of adjacent mechanical intervention.

Adult dialysis patients with angina pectoris refractory to medical treatment or revascularization are not uncommon. Enhanced external counterpulsation (EECP) has been proven to be effective in reducing myocardial ischemia and refractory angina. The objective of this study was to assess the immediate and 1-year effects of EECP treatment in dialysis patients with refractory angina. Thirty-six consecutive dialysis patients were treated with EECP, and a follow-up was conducted after 1 year. The Canadian Cardiovascular Society (CCS) Angina Grading Scale was used to measure angina severity. Medications were recorded before EECP treatment, at the end of treatment, and at 1-year follow-up. Adverse events and risk factors of cardiovascular disease were recorded and analyzed. At 1-year follow-up, data from patients improving by at least one CCS class after treatment were compared with data from patients showing no improvement. The improvement rates in CCS class were 85% immediately after EECP and 66% at 1-year follow-up. Thallium-201 myocardial perfusion imaging demonstrated a reversible resolution of 40% and improvement of 25% immediately after EECP treatment. Diabetes mellitus and high serum phosphate levels were risk factors affecting whether the beneficial effects of EECP treatment could be sustained (p < 0.05). Major adverse events were rare. EECP shows potential for refractory angina in dialysis patients. The beneficial effects were sustained for more than 1 year in 66% patients. Diabetes mellitus and high serum phosphate levels were major factors impacting the sustained effectiveness of EECP treatment. Nonetheless, adequately powered future studies are necessary to assess safety and efficacy of this procedure.

The anti-oxidant effects of epigallocatechin gallate (EGCG) and alpha lipoic acid (ALA) have been demonstrated in previous studies. The kidney protection effects of EGCG and ALA in patients with kidney injury are still under investigation. The purpose of this study is to investigate the anti-inflammatory and anti-oxidant effects of EGCG and ALA on high glucose-induced human kidney cell damage. EGCG inhibited high glucose(HG)-induced TNF-α and IL-6 production in human embryonic kidney (HEK) cells. Both EGCG and ALA decreased HG-induced receptor of advanced glycation end products (RAGE) mRNA and protein expressions in HEK cells. EGCG and ALA also recovered HG-inhibited superoxide dismutase production and decreased ROS expressions in HEK cells. The synergism of EGCG and ALA was also studied. The effect of EGCG combined with ALA is greater than the effect of EGCG alone in all anti-inflammation and anti-oxidant experiments. Our studies provide a potential therapeutic application of EGCG and ALA in preventing progression of diabetic nephropathy.Os efeitos antioxidantes de galato de epigalocatequina (EGCG) e ácido alfa lipóico (ALA) foram demonstrados em estudos anteriores. Os efeitos renais da proteção de EGCG e ALA em pacientes com lesão renal ainda estão sob investigação. A finalidade deste estudo é investigar os efeitos anti-inflamatórios e antioxidantes de EGCG e ALA em lesão de células de rim humano induzida pela alta glicose. EGCG inibiu a produção de TNF-α e IL-6 induzida por HG em células de rim embrionário humano (HEK). Ambos EGCG e ALA diminuíram o mRNA do receptor de produtos finais de glicação avançada (RAGE) induzida por HG e a expressão de proteínas em células HEK. EGCG e ALA também recuperaram a produção de superóxido dismutase inibida por HG e diminuíram a expressão de ROS em células HEK. O sinergismo de EGCG e ALA também foi estudado. O efeito de EGCG combinado com ALA é maior do que o efeito de EGCG sozinho em todos os experimentos anti-inflamatórios e antioxidantes. Os nossos estudos fornecem uma potencial aplicação terapêutica do EGCG e ALA na prevenção da progressão de nefropatia diabética.

Background Acute thrombosis of a transplanted renal artery is a serious vascular complication following renal allograft transplantation, which usually occurs within the first month after transplantation and often results in graft loss. It rarely occurs beyond the first month, except in a rejected kidney or in a kidney with high-grade transplant renal artery stenosis. Result A 65-year-old male with a history of type 2 diabetes mellitus, hypertension, pulmonary tuberculosis, and end-stage renal disease was previously treated with hemodialysis (HD). He received a kidney transplant and had a well-functioning graft for 2 years. He presented to our emergency department with gastric ulcer bleeding and received treatment involving an endoscopic submucosal epinephrine injection, a proton pump inhibitor, and blood transfusions. Nine days later, he complained of sudden lower abdominal pain and had acute anuric kidney failure. Renal ultrasonography revealed an absence of blood flow to the allograft kidney. Renal artery angiogram demonstrated complete occlusion of the transplanted renal artery. After thrombectomy and percutaneous transluminal angioplasty (PTA) with stent placement, 60% stenosis of the proximal renal artery with distal perfusion was noted. However, his graft function did not improve, and he received HD again. Histopathology of the transplanted kidney revealed ischemic tubular nephropathy with focal infarction without rejection. Conclusion This is the first case of acute thrombosis of the transplanted renal artery following gastric ulcer bleeding in a patient with a long-term well-functioning graft kidney.

Taxol, originally extracted from the bark of the western yew, Taxus brevifolia, is reportedly the first of a new class of anti-cancer agents. It acts by promoting and irreversibly stabilizing microtubule assembly, thus interfering with the dynamic processes required for cell viability and multiplication. With the aim of using immunological techniques to study the mechanism of action of taxol, a monoclonal anti-idiotypic antibody that mimics taxol was prepared, using an auto-anti-idiotypic strategy. It and its Fab fragment inhibited the binding of [3H]taxol to microtubules. Moreover, like taxol, both promoted the assembly of tubulin into microtubules. These findings provide an example of an anti-idiotypic antibody capable of assembling an organized supramolecular structure from soluble cellular components. In addition, it further establishes the ability of anti-idiotypic antibodies to be functional mimics of ligand molecules bearing no structural similarity to immunoglobulins. The variable regions of the antibody have been sequenced. With the exception of the complementarity-determining region 3, the sequence of the heavy chain variable region is strikingly similar to that of an anti-idiotypic antibody raised to anti-insulin. The finding that a polypeptide can mimic taxol raises the possibility that taxol acts as a peptidomimetic compound that interferes with the function of an endogenous polypeptide.

The renoprotective effect and safety of an angiotensin II receptor blocker, losartan, were studied in 11 diabetic and 14 nondiabetic patients with a daily urinary protein excretion >500 mg. Once-daily losartan was administered to all patients for 16 weeks without diuretics or other antihypertensive agents. A daily dose of 50 mg was given to those patients with a sitting systolic blood pressure of between 130 and 170 mm Hg; 25 mg was given to patients with a systolic blood pressure of between 110 and 130 mm Hg. Sixteen patients (6 diabetic and 10 nondiabetic patients) had a more than 25% decrease of their daily urinary protein excretion (response rate 64%). The mean decrease in these 16 patients was 57 ± 17% (p < 0.05). Two patients (1 diabetic and 1 nondiabetic) had more than a 25% increase of their urinary protein excretion. The trough sitting systolic blood pressure of all patients (n = 25) decreased from 142 ± 17 to 125 ± 13 mm Hg (p < 0.05) and the trough sitting diastolic blood pressure from 87 ± 11 to 78 ± 11 mm Hg (p < 0.05). Serum uric acid was measured in 16 patients; a decrease from 7.3 ± 1.6 to 6.6 ± 1.4 mg/dl (a 9.6% decrease, p < 0.05) was found after 16 weeks. Our study showed that in both diabetic and nondiabetic proteinuric patients once-daily losartan, given as monotherapy at doses of 25 or 50 mg, was effective in reducing blood pressure, serum uric acid levels, and daily urinary protein excretions.

C-reactive protein (CRP) has emerged as a new marker for cardiovascular diseases. Activation of peroxisome proliferator-activated receptor delta (PPARdelta) plays beneficial roles in cardiac disorders. However, the relationship between CRP and PPARdelta in cardiac cells remains unclear. This study focused on the underlying molecular mechanisms of CRP and PPARdeltaagonists. Cardiomyocytes and cardiomyoblast cell line (H9c2) were used in different groups: Untreated; 15 microg/ml CRP with or without 1 microM PPARdelta agonists (L-165041). CRP increased PPARdelta and interleukin-6 expression in cardiomyocytes and H9c2 cardiomyoblasts. NF-kappaB inducing kinase (NIK) and NF-kappaB pathway also activated by CRP stimulation. These changes could be inhibited by L-165041 through p38MAPK and c-JNK pathways. However, transfection with siRNA of CD32 CRP receptor did not decrease CRP signaling or reverse the effects of L-165041 in CRP-treated cardiomyocytes and H9c2. Pretreatment with L-165041 attenuated apoptosis induced by hypoxia with or without CRP in H9c2 cardiomyoblasts. CRP up-regulated PPARdelta expression in cardiomyocytes and H9c2. L-165041 attenuated CRP-induced pro-inflammatory signaling through p38MAPK and c-JNK in H9c2 cardiomyoblasts. However, PPARdelta activation attenuated CRP-induced NF-kappaB pathway may be independent of CD32. These results may provide new evidence of PPARdelta beneficial effects for inflammatory cardiomyopathy.

Thyrotoxic periodic paralysis (TPP) is characterized by the presence of muscle paralysis, hypokalemia, and hyperthyroidism. We report the case of a young man with paralysis of the lower extremities, severe hypokalemia, and concurrent hyperthyroidism. TPP was suspected; therefore, treatment consisting of judicious potassium (K+) repletion and β-blocker administration was initiated. However, urinary K+ excretion rate, as well as refractoriness to treatment, was inconsistent with TPP. Chronic alcoholism was considered as an alternative cause of hypokalemia, and serum K+ was restored through vigorous K+ repletion and the addition of K+-sparing diuretics. The presence of thyrotoxicosis and hypokalemia does not always indicate a diagnosis of TPP. Exclusion of TPP can be accomplished by immediate evaluation of urinary K+ excretion, acid-base status, and the amount of potassium chloride required to correct hypokalemia at presentation.

A 44-year-old uremic woman presented with a 2-week history of painless hematuria. This oliguric patient has been under regular hemodialysis for 2 years as a result of Chinese herb nephropathy. Atypical cells were found in urine cytologic examinations. Ultrasound findings only suggested both kidneys were not visible. PET/CT scan revealed bilateral contracted kidneys and a focal increased uptake of 18-fluoro-2-deoxyglucose (FDG) in the upper portion of the left kidney. No obvious accumulation of FDG was found in other portions of the urinary tract. Coregistration CT scan also revealed a soft tissue lesion in the upper pole of the left kidney. Ten days after the PET/CT scan, MRI images revealed that both kidneys were severely contracted with loss of normal corticomedullary differentiation. An ill-defined heterogeneously enhancing mass in the upper pole of the left kidney corresponded to the PET findings. The patient received a left nephroureterectomy and bladder cuff excision. A protruding renal pelvic tumor, 1 cm in diameter, was found. Microscopic pathologic examination showed a WHO grade 3 transitional cell carcinoma. No malignancy was noted in the left ureter or urinary bladder cuff.

Objective: Serotonin via serotonin 2B receptors (SR2BR) regulates cardiac embryonic development and adult heart functions. However, the role of SR2BR in the failing heart due to pressure overload is not well understood. Methods: Wistar rats of aortic banding and neonatal cardiomyocyte with mechanical stretch were used as cardiomyopathy models. Results: After two weeks of aortic banding surgery, serum serotonin, mRNA and protein expression of SR2BR increased significantly. The selective SR2BR antagonist, SB215505 (SB), significantly reduced the increase in heart weight, decreased heart wall thickness, left ventricular mass and the expression of the brain natriuretic peptide (BNP) but did not attenuate the up-regulation of SR2BR protein expression in rats after aortic banding for three weeks. After following in vitro mechanical stretch of cardiomyocytes and incubation with serotonin 1 μM, the level of SR2BR and BNP protein increased time-dependently. When transfected by specific siRNA of SR2BR or pretreated with caffeic acid phenethyl ester in cardiomyocytes, the increase of nuclear factor-κB (NF-κB) translocation and BNP protein induced by serotonin incubation plus mechanical stretch were both reversed. Conclusions: SR2BR expression is involved in pressure-induced cardiomyopathy and its downstream signaling may involve NF-κB to modulate BNP expression in cardiomyocyte.