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Objective: Heart failure (HF) imposes a substantial burden and the prevalence of HF is high in patients with chronic kidney disease (CKD). HF results in multiple hospital admissions, but whether HF subtypes worsen long-term outcomes and renal function in patients with CKD remains inconclusive.Methods: The study comprised 10 904 patients with CKD aged ≥20 years who underwent echocardiography between 1 January 2011 and 31 December 2018. The patients were stratified into four groups: non-HF, HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF) and HF with preserved ejection fraction (HFpEF). The primary end points were all-cause mortality, major adverse cardiovascular events (MACEs) and adverse renal outcomes.Results: In inverse probability of treatment weighting-adjusted method, the risk of all-cause mortality and MACEs relative to the non-HF group was greatest in the HFrEF group (HR 3.18 (95% CI 2.57 to 3.93) and HR 3.83 (95% CI 3.20 to 4.59)), followed by the HFmrEF (HR 2.75 (95% CI 2.22 to 3.42) and HR 3.08 (95% CI 2.57 to 3.69)) and HFpEF (HR 1.85 (95% CI 1.59 to 2.15) and HR 2.43 (95% CI 2.16 to 2.73) groups. In addition, the HFrEF group had the greatest risks of end-stage renal disease (HR 2.58 (95% CI 1.94 to 3.44)) compared with other groups.Conclusions: HF is associated with subsequent worse clinical outcomes, which may be more pronounced in patients with HFrEF, followed by those with HFmrEF and those with HFpEF relative to non-HF group. [ABSTRACT FROM AUTHOR]

Background: Decoy receptor 3 (DcR3) belongs to the tumor necrosis factor (TNF) receptor superfamily and neutralizes TNF ligands, including FasL and TRAIL, to prevent T activation during T-cell priming. However, the cellular mechanisms underlying acute cellmediated rejection (ACMR) remain unknown. Methods: We generated DcR3 transgenic (Tg) mice and mice with high DcR3 expression (HDE) to study both in vivo and in vitro. FasR RNA knockdown in immortalized CD4+CD8+ T-cells was used to survey the role of DcR3 on FasR/Fas-associated protein with death domain (FADD)/caspase 8 pathway and its cross-link to TNF receptor-associated factor 1 (TNFR1)-associated death domain protein (TRADD) in suppressing TNFR1. TNF/TRADD knockout mice were used to show the importance of TNF adaptor protein. Results: DcR3.Fc suppressed C57BL/6 female T-cell activation and transformation into CD4+CD69+, CD4+CD44+, and CD4+CD25+Foxp3+ when compared with isotype IgG1 and its co-treatment with FasL/TRAIL after exposing to bone marrow-derived dendritic cells (BMDCs) that carried alloantigen with male H-Y and minor antigenic determinant. Interleukin-17 and interferon-g productions by BMDC-activated T-cells were lowered after co-treating with DcR3.Fc. DcR3.Fc induced effector T-cells (Teffs) and was susceptible to FasR-mediated apoptosis through the FADD/TRADD/caspase 8 pathway. After exposing to DcR3.Fc, TRADD was silenced, likely turning down the inflammatory response. The systemic effects of DcR3 Tg mice and HDE phenotype induced by the promoter of cytomegalovirus not only attenuated ACMR severity but also ameliorated the high serum creatinine and blood urea nitrogen levels even with high T-cell exposure frequencies. Besides this, DcR3 has minor biological effects on both MHC-matched and MHCmismatched models. Conclusions: High DcR3 doses protect renal tubular epithelial cells from acute T-cell attack during the T-cell priming stage via interfering with TNF ligand-mediated reverse signaling and possibly promoting Teff apoptosis through FasR upregulation. Our findings supported that the decoy receptor is involved in T-cell modulation in kidney transplant rejection. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is known to increase the risk of atrial fibrillation (AF) development, but the relationship between AF and subsequent renal function decline in patients with CKD is not well understood. In this study, we explored the role of AF on renal outcomes among patients with CKD.Methods: In a retrospective hospital-based cohort study, we identified patients with CKD aged ≥20 years from 1 January 2008 to 31 December 2018. The patients were divided into AF and non-AF groups. We matched each patient with CKD and AF to two non-AF CKD controls according to propensity scores. The outcomes of interest included estimated glomerular filtration rate (eGFR) decline of ≥20%, ≥30%, ≥40% and ≥50%, and end-stage renal disease (ESRD).Results: After propensity score matching, 6731 patients with AF and 13 462 matched controls were included in the analyses. Compared with the non-AF group, the AF group exhibited greater risks of eGFR decline ≥20% (HR 1.43; 95% CI 1.33 to 1.53), ≥30% (HR 1.50; 95% CI 1.36 to 1.66), ≥40% (HR 1.62; 95% CI 1.41 to 1.85) and ≥50% (HR 1.82; 95% CI 1.50 to 2.20), and ESRD (HR 1.22; 95% CI 1.12 to 1.34). Higher CHA2DS2-VASc scores were associated with greater risks of eGFR decline and ESRD.Conclusions: In patients with CKD, AF was associated with greater risks of subsequent renal function decline. CHA2DS2-VASc scores may be a useful risk stratification scheme for predicting the risk of renal function decline. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI)-related fibrosis is emerging as a major driver of chronic kidney disease (CKD) development. Aberrant kidney recovery after AKI is multifactorial and still poorly understood. The accumulation of indoxyl sulfate (IS), a protein-bound uremic toxin, has been identified as a detrimental factor of renal fibrosis. However, the mechanisms underlying IS-related aberrant kidney recovery after AKI is still unknown. The present study aims to elucidate the effects of IS on tubular damage and its involvement in the pathogenesis of AKI-to-CKD transition. Our results showed that serum IS started to accumulate associated with the downregulation of tubular organic anion transporter but not observed in the small-molecule uremic toxins of the unilateral ischemia-reperfusion injury (UIRI) without a contralateral nephrectomy model. Serum IS is positively correlated with renal fibrosis and binding immunoglobulin protein (BiP) and CAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) expression induction in the UIRI with a contralateral nephrectomy model (UIRI+Nx). To evaluate the effects of IS in the AKI-to-CKD transition, we administered indole, a precursor of IS, at the early stage of UIRI. Our results demonstrated IS potentiates renal fibrosis, senescence-associated secretory phenotype (SASP), and activation of endoplasmic reticulum (ER) stress, which is attenuated by synergistic AST-120 administration. Furthermore, we clearly demonstrated that IS exposure potentiated hypoxia-reperfusion (H/R) induced G2/M cell cycle arrest, epithelial-mesenchymal transition (EMT) and aggravated ER stress induction in vitro. Finally, the ER chemical chaperon, 4-phenylbutyric acid (4-PBA), successfully reversed the above-mentioned AKI-to-CKD transition. Taken together, early IS elimination in the early stage of AKI is likely to be a useful strategy in the prevention and/or treatment of the AKI-to-CKD transition. [ABSTRACT FROM AUTHOR]

Transcriptional co-activator with PDZ-binding motif (TAZ) is a key downstream effector of the Hippo tumor-suppressor pathway. The functions of TAZ in the kidney, especially in tubular epithelial cells, are not well-known. To elucidate the adaptive expression, protective effects on kidney injury, and signaling pathways of TAZ in response to acute kidney injury (AKI), we used in vitro (hypoxia-treated human renal proximal tubular epithelial cells [RPTECs]) and in vivo (mouse ischemia-reperfusion injury [IRI]) models of ischemic AKI. After ischemic AKI, TAZ was up-regulated in RPTECs and the renal cortex or tubules. Up-regulation of TAZ in RPTECs subjected to hypoxia was controlled by IκB kinase (IKK)/nuclear factor γ-light-chain-enhancer of activated B cell (NF-κB) signaling. TAZ overexpression attenuated hypoxic and oxidative injury, inhibited apoptosis and activation of p38 and c-Jun N-terminal kinase (JNK) proteins, and promoted wound healing in an RPTEC monolayer. However, TAZ knockdown aggravated hypoxic injury, apoptosis, and activation of p38 and JNK signaling, delayed wound closure of an RPTEC monolayer, and promoted G0/G1 phase cell-cycle arrest. Chloroquine and verteporfin treatment produced similar results to TAZ overexpression and knockdown in RPTECs, respectively. Compared with vehicle-treated mice, chloroquine treatment increased TAZ in the renal cortex and tubules, improved renal function, and attenuated tubular injury and tubular apoptosis after renal IRI, whereas TAZ siRNA and verteporfin decreased TAZ in the renal cortex and tubules, deteriorated renal failure and tubular injury, and aggravated tubular apoptosis. Our findings indicate the renoprotective role of tubular TAZ in ischemic AKI. Drugs augmenting (e.g., chloroquine) or suppressing (e.g., verteporfin) TAZ in the kidney might be beneficial or deleterious to patients with AKI. [ABSTRACT FROM AUTHOR]

Objective We compared the incidence and risk of chronic kidney disease (CKD) between subjects with new-onset migraine and matched controls without migraine in this large-scale retrospective cohort study. Design Population-based cohort study. Setting 8880 subjects with migraine and 503 070 subjects without migraine were enrolled between January 1, 2000 and December 31, 2013, all diagnosed to be without kidney disease. All the participants were registered in the National Health Insurance Research Database. Participants Finally, data from 7156 subjects with migraine and 7156 propensity-score-matched control subjects were analysed. Primary outcome measure We used Cox proportional hazards regression to estimate adjusted HRs for incident CKD; subgroup analyses were performed to assess the interactive effects of migraine with demographics, comorbidities and long-term medications. Results The incidence of CKD was higher in the migraine group than in the control group. The risk of developing CKD was significantly higher in subjects with migraine than without migraine (P=0.031). Subjects with migraine aged <65 years (age 40–64 (adjusted HR (aHR) 1.35; 95% CI 1.05 to 1.73); age <40 (aHR 1.55; 95% CI 1.02 to 2.36)), with ≥1 comorbid diseases (1–2 diseases (aHR 1.30; 95% CI 1.01 to 1.68); ≥3 diseases (aHR 1.45; 95% CI 1.01 to 2.07)), and not receiving anti-migraine agents (aHR 1.26; 95% CI 1.04 to 1.54) were at a higher risk of developing CKD compared with the control subjects. The interaction between migraine and comorbidities was not significant; age, male gender and long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) were independent risk factors for CKD in subjects with migraine. Conclusion Migraine may be an independent risk factor for CKD. Young subjects with migraine, and those with comorbid conditions or without medical control, are likely to be at higher risk for CKD. Ageing, male sex and NSAIDs tend to have an association with CKD in subjects with migraine. [ABSTRACT FROM AUTHOR]

Objectives To investigate the impact of vascular access flow (Qa) on vascular and all-cause mortality in chronic haemodialysis (HD) patients. Design Observational cohort study. Setting Single centre. Participants Adult 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 <18 years and had Qa levels of ≥2000mL/min. A total of 378 adult chronic HD patients were eventually enrolled for the study. Interventions The 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 measures Short-term and long-term vascular (cardiovascular or cerebrovascular) and all-cause mortality. Results Qa was positively correlated with CI (r=0.48, p<0.001). A Qa level of <1000 mL/min was independently associated with 1-year all-cause mortality (adjusted OR, 6.04; 95% CI 1.64 to 22.16; p=0.007). Kaplan-Meier analysis revealed that the cumulative incidence rates of all-cause and vascular mortality were significantly higher in the patients with a Qa level of <1000 mL/min (log-rank test; all p<0.01). Furthermore, a Qa level of <1000 mL/min was independently associated with long-term all-cause mortality (adjusted HR, 1.62; 95% CI 1.11 to 2.37; p=0.013); however, the risk of vascular mortality did not significantly increase after adjustment for confounders. Conclusions Qa is moderately correlated with cardiac function, and a Qa level of <1000 mL/min is an independent risk factor for both short-term and long-term all-cause mortality in chronic HD patients. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) have an increased risk of vascular disease, which is associated with considerable health care costs. Vascular disease in CKD differs clinically and pathobiologically from that in patients with normal renal function. Besides the traditional risk factors, retention of uremic toxins contributes to the pathogenesis of vascular disease in patients with CKD. Indoxyl sulfate is a protein-bound uremic toxin and is inefficiently removed by conventional dialysis. Accumulating evidence suggests that indoxyl sulfate is a vascular toxin involved in atherosclerosis, arteriosclerosis, vascular calcification and vascular repair. Clinically, indoxyl sulfate is associated with total and cardiovascular mortality in patients with CKD. Recent studies have indicated that in addition to coronary and cerebral arteries, indoxyl sulfate plays a role in peripheral artery disease (PAD) and dialysis graft thrombosis. Emerging evidence suggests that indoxyl sulfate is implicated via novel mechanisms, including progenitor cell-related neovascularization and tissue factor-related hypercoagulability. These findings raise the possibility that strategies targeting serum indoxyl sulfate may have the potential to improve the outcomes of PAD and dialysis vascular access in patients with CKD. [ABSTRACT FROM AUTHOR]

High uric acid (UA) can act as a pro-oxidant in normal physiological conditions; however, emerging evidence is still debatablewith regard to the association between highUAand poor outcomes among chronic hemodialysis (HD) patients. In the present study, 27,229 stable prevalent HD patients were enrolled and divided into four groups according to the quartiles of baseline UA concentration, and 5737 died during a median follow-up of 38 months. Multivariate Cox regression analysis showed that a UA level of <6.1 mg/dL was associated with a higher risk of all-cause mortality compared with a UA level of >8.1 mg/dL [HR, 1.20, 95% CI (1.10-1.31)] adjusting for baseline demographic and biochemical parameters. Moreover, a UA level of <6.1 mg/dL was associated with greater risks of cardiovascular mortality [HR, 1.26, 95% CI (1.13-1.41)] and stroke-related mortality [HR, 1.59, 95% CI (1.12-2.25)], respectively. In vitro experiments further showed an increase in oxidative stress and an inhibition nitric oxide synthesis by indoxyl sulfate (IS) in human aortic endothelial cells, which were significantly attenuated by UA in a dose-dependent manner. We concluded that higher UA in serum was associated with lower risk of all-cause and cardiovascular mortality among HD patients probably through its antioxidant property in ameliorating the IS-related vascular toxicity. [ABSTRACT FROM AUTHOR]

Catheter-related blood stream infection (CRBSI) is a major complication in hemodialysis patients. We assessed the efficacy of systemic daptomycin (DPT) plus DPT antibiotic lock therapy (DPT-ALT) for catheter salvage in patients with Gram-positive CRBSIs. This is a retrospective study of hemodialysis patients with tunneled and cuffed hemodialysis catheters. All patients were from a single institution in Taipei and received systemic DPT plus DPT-ALT for the treatment of Gram-positive CRBSI. Successful resolution of CRBSI was implemented. Resolution of fever within 48 hours, negative result of repeated blood cultures after resolution of fever, no clinical evidence of CRBSI relapse and no need for catheter removal were measured. Fifteen hemodialysis patients received DPT-ALT for CRBSI, nine with coagulase-negative Staphylococcus (CONS), two with methicillin-resistant Staphylococcus aureus (MRSA), three with methicillin-sensitive Staphylococcus aureus (MSSA) and one with polymicrobial infections. Systemic DPT plus DPT-ALT cured 11 patients (73.3%). Treatment failed in all three MRSA cases (two with MRSA and one with MRSA + Enterococcus faecalis). Retrospective design and small sample size were the limitations of this study. Systemic DPT plus DPT-ALT appears to be a promising treatment for CRBSI from CONS and MSSA, but not for MRSA CRBSI. Systemic DPT plus DPT-ALT should be considered for patients with CRBSIs caused by certain species. [ABSTRACT FROM AUTHOR]

Background: Fibrillary glomerulonephritis (FGN) is a rare primary glomerular disease that seldom coexists with other diseases. Membranoproliferative glomerulonephritis is a pathologic finding of renal lesions associated with IgM-secreting monoclonal proliferations. We present a case study of a patient with unusual simultaneous FGN and IgM-related renal disorder in nonmalignant monoclonal IgM gammopathy.Case Presentation: A 63-year-old male presented with nephrotic syndrome and elevated serum creatinine levels. Laboratory examination revealed elevated levels of serum IgM and low C3 levels. Serum and urine immunofixation electrophoresis showed a monoclonal IgM with a kappa light chain. A bone marrow biopsy revealed less than 5 % bone marrow infiltration by lymphoplasmacytic lymphoma, and a renal biopsy revealed mesangiocapillary glomerulonephritis on light microscopy. Immunofluorescent and immunohistochemical staining indicated granular deposits of immunoglobulin G in the mesangium and granular deposits of immunoglobulin M and κ light chains along the capillary wall. Electron microscopy revealed randomly arranged nonbranching fibrils of approximately 15 nm in diameter in the glomerular mesangium and subendothelial electron-dense deposits. According to these results, we confirmed FGN and membranoproliferative glomerulonephritis, which were attributed to monoclonal IgM deposits.Conclusion: To the best of our knowledge, this is the first report of simultaneous FGN and membranoproliferative glomerulonephritis in nonmalignant IgM monoclonal gammopathy. [ABSTRACT FROM AUTHOR]

Background: Recent studies concluded that dipeptidyl peptidase-4 (DPP-4) inhibitors provide glycemic control but also raised concerns about the risk for heart failure in patients with type 2 diabetes mellitus (T2DM). However, large-scale studies of the effects on cardiovascular outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy remain scarce.Objective: To compare clinical outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy in patients with T2DM.Design: Nationwide study using Taiwan's National Health Insurance Research Database.Setting: Taiwan.Patients: All patients with T2DM aged 20 years or older between 2009 and 2012. A total of 10,089 propensity score-matched pairs of DPP-4 inhibitor users and sulfonylurea users were examined.Measurements: Cox models with exposure to sulfonylureas and DPP-4 inhibitors included as time-varying covariates were used to compare outcomes. The following outcomes were considered: all-cause mortality, major adverse cardiovascular events (MACEs) (including ischemic stroke and myocardial infarction), hospitalization for heart failure, and hypoglycemia. Patients were followed until death or 31 December 2013.Results: DPP-4 inhibitors were associated with lower risks for all-cause death (hazard ratio [HR], 0.63 [95% CI, 0.55 to 0.72]), MACEs (HR, 0.68 [CI, 0.55 to 0.83]), ischemic stroke (HR, 0.64 [CI, 0.51 to 0.81]), and hypoglycemia (HR, 0.43 [CI, 0.33 to 0.56]) compared with sulfonylureas as add-on therapy to metformin but had no effect on risks for myocardial infarction and hospitalization for heart failure.Limitation: Observational study design.Conclusion: Compared with sulfonylureas, DPP-4 inhibitors were associated with lower risks for all-cause death, MACEs, ischemic stroke, and hypoglycemia when used as add-ons to metformin therapy.Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

Background. A risk/benefit analysis of iron supplementation in pre-dialysis advanced chronic kidney disease (CKD) patients has not been conducted. We aim to assess the effectiveness and the safety of iron supplementation in patients with CKD Stage 5 who have not yet received dialysis (CKD 5 ND). Methods. A prospective cohort study was conducted based on the Taiwan National Health Insurance Research Database. From 1 January 2000 to 30 June 2009, we enrolled 31 971 adult patients who had a serum creatinine >6 mg/dL and a haematocrit <28% and who were treated with erythropoiesis- stimulating agents (ESAs). All patients were further divided into two groups with or without iron supplementation within 90 days after starting ESA therapy. Patient follow-up took place until dialysis, death before initiation of dialysis or 31 December 2009. The primary outcomes were death before initiating dialysis, hospitalization before death or long-term dialysis. Results. After propensity score matching, the patients who received iron supplementation were associated with a lower risk of all-cause death [hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.80-0.90] compared with non-users. The survival benefit of iron use was consistent across the majority of dosage groups, except for those who were treated with monthly IV iron >200 mg. Moreover, compared with the non-users, the iron users were associated with a lower risk of hospitalizations (HR, 0.97; 95% CI, 0.94-0.99) but with a higher risk of faster progression to end-stage renal disease (HR, 1.05; 95% CI, 1.01-1.08). Conclusions. Iron supplementation is associated with 15% risk reduction in death among CKD 5NDpatients who received ESA treatment. Randomized studies are needed to validate this association. [ABSTRACT FROM AUTHOR]

Background: Older patients with advanced chronic kidney disease (CKD) face the decision of whether to undergo dialysis. Currently available data on this issue are limited because they were generated by small, short-term studies with statistical drawbacks. Further research is urgently needed to provide objective information for dialysis decision making in older patients with advanced CKD. Methods: This nationwide population-based cohort study was conducted using Taiwanfs National Health Insurance Research Database. Data from 2000 to 2010 were extracted. A total of 8,341 patients ≥70 years old with advanced CKD and serum creatinine levels >6 mg/dl, who had been treated with erythropoiesis-stimulating agents were included. Cox proportional hazard models in which initiation of chronic dialysis was defined as the time-dependent covariate were used to calculate adjusted hazard ratios for mortality. The endpoint was all-cause mortality. Results: During a median follow-up period of 2.7 years, 6,292 (75.4%) older patients chose dialysis therapy and 2,049 (24.6%) received conservative care. Dialysis was initiated to treat kidney failure a median of 6.4 months after enrollment. Dialysis was associated with a 1.4-fold increased risk of mortality compared with conservative care (adjusted hazard ratio 1.39, 95% confidence interval 1.30 to 1.49). In subgroup analyses, the risk of mortality remained consistently increased, independent of age, sex and comorbidities. Conclusions: In older patients, dialysis may be associated with increased mortality risk and healthcare cost compared with conservative care. For patients who are ≥70 years old with advanced CKD, decision making about whether to undergo dialysis should be weighted by consideration of risks and benefits. [ABSTRACT FROM AUTHOR]

Background: The association between intravenous (IV) iron administration and outcomes in hemodialysis (HD) patients is still debated. Therefore, this study was aimed to assess the relationship between the IV administration of ferric chloride hexahydrate (Atofen®) and cardiovascular (CV) outcome and the interaction between iron-induced oxidative stress and endothelial dysfunction in chronic HD patients. Methodology/Principal Findings: A cohort of 1239 chronic HD patients was recruited. In a follow-up of 12 months, Kaplan- Meier survival curves showed that higher doses of IV Atofen associated with higher risks for CV events and deaths in HD patients. In multivariate Cox models, compared to no iron supplementation, IV Atofen administration was an independent predictor for CV events and overall mortality. However, the nature of the observational cohort study possibly bears selection bias. We further found that IV Atofen enhanced the superoxide production of mononuclear cells (MNCs), the levels of circulating soluble adhesion molecules, and the adhesion of MNCs to human aortic endothelial cells (HAECs). In vitro experiments showed that Atofen increased the expression of intracellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 in HAECs and aggravated the endothelial adhesiveness in a dose-dependent manner. These ironinduced changes were significantly attenuated by the co-treatment of HAECs with N-acetylcysteine and inhibitors of NADPH oxidase, nuclear factor κB, and activator protein-1. Conclusion: A cumulative dose of IV Atofen >800 mg within 6 months was associated with an adverse CV outcome and a higher mortality among chronic HD patients. The detrimental effects of IV iron supplementation were partly due to the increased oxidative stress and induction of MNC adhesion to endothelial cells, a pivotal index of early atherogenesis. [ABSTRACT FROM AUTHOR]

Background: The renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of chronic kidney disease (CKD). Although dual RAAS inhibition results in worse renal outcomes than monotherapy in high risk type 2 diabetes patients, the effect of dual RAAS inhibition in patients with non-DM CKD is unclear. The aim of this study was to evaluate the potential renoprotective effect of add-on direct renin inhibitor in non-DM CKD patients. Methods: We retrospectively enrolled 189 non-DM CKD patients who had been taking angiotensin II receptor blockers (ARBs) for more than six months. Patients were divided into an add-on aliskiren group and an ARB monotherapy group. The primary outcomes were a decline in glomerular filtration rate (GFR) and a reduction in urinary protein-to-creatinine ratio at six months. Results: The baseline characteristics of the two groups were similar. Aliskiren 150 mg daily reduced the urinary protein-to-creatinine ratio by 26% (95% confidence interval, 15 to 37%; p < 0.001). The decline in GFR was smaller in the add-on aliskiren group (-2.1 vs. -4.0 ml/min, p = 0.038). Add-on aliskiren had a neutral effect on serum potassium in the non-DM CKD patients. In subgroup analysis, the proteinuria-reducing effect of aliskiren was more prominent in patients with a GFR less than 60 ml/min, and in patients with a urinary protein-to-creatinine ratio greater than 1.8. The effect of aliskiren in retarding the decline in GFR was more prominent in patients with hypertensive nephropathy than in those with glomerulonephritis. Conclusion: Add-on direct renin inhibitor aliskiren (150 mg daily) safely reduced proteinuria and attenuated the decline in GFR in the non-DM CKD patients who were receiving ARBs. [ABSTRACT FROM AUTHOR]

Elevated levels of serum pancreatic enzymes are frequently observed in hemodialysis (HD) patients. The complex hemodynamic, biochemical, and physiological alterations in uremia were speculated to cause excessive release of pancreatic enzymes beyond decreased renal clearance. However, hemodynamic factors are seldom explored in this aspect. We performed the study to evaluate the association between intradialytic hemodynamic change and elevated serum pancreatic amylase (SPA). Eighty-three prevalent HD patients without any clinical evidence of acute pancreatitis underwent pre-HD and post-HD blood sampling for serum pancreatic enzyme levels. Demographic, biochemical, and hematological data were collected from patient record review. Hemodialysis information including intradialytic blood pressure changes and ultrafiltration (UF) amount were collected and averaged for 1 month before the blood sampling day. Patients with elevated SPA during the HD session had greater mean systolic blood pressure and mean arterial pressure reduction, greater UF volume, greater pre-HD blood urea nitrogen and serum creatinine, higher serum phosphorus, lower pre-HD serum total CO, and lower left ventricle ejection fraction (LVEF). Using multivariate linear and logistic regression analysis, the independent predictors of elevated SPA were determined to be mean arterial pressure reduction during HD, mean UF amount, pre-HD serum total CO, and LVEF. Greater blood pressure reduction during HD, greater UF volume, lower pre-HD serum total CO, and lower LVEF were significantly associated with elevated SPA during HD. This suggests that hemodynamic factors contribute to elevated serum pancreatic enzymes in HD patients. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) have been employed as immunosuppressive agents for many years. However, it is still unclear how GCs instantly uncouple T cells from acute stressful inflammatory. In terms of time scale, the genomic activity of the classic GC receptor cannot fulfill this role under crisis; but a rapid non-genomic response can. In a previous study, intracellular acidification was found to be due to a rapid non-genomic inhibition of Na+/H+-exchange 1 (NHE1) and this event led to the immunosuppression of T cell proliferation by progesterone. The aim of this study was to examine whether there is a rapid acidification response caused by an inhibition of NHE1 activity and to explore the differential non-genomic effect on immunosuppression of hydrocortisone and dexamethasone. The IC50 values for NHE1-dependent pHi recovery by hydrocortisone and dexamethasone are 250 and 1 nM, respectively. Co-stimulation of GCs with phytohemagglutinin (PHA) is able to inhibit PHA-induced IL-2 secretion, IL-4 secretion, and T-cell proliferation. Furthermore, apoptosis in PHA-activated T cells is not induced by hydrocortisone but by dexamethasone. The mechanism of immunosuppression on proliferation by dexamethasone was found to be different of hydrocortisone and seems to involve cytotoxicity against T cells. Moreover, apoptosis induced by dexamethasone and impermeable dexamethasone–bovine serum albumin suggests that the apoptotic immunosuppression occurs through both the plasma membrane and cytoplasmic sites. The rapid inhibitory responses triggered by GCs would seem to release T cells instantly when an acute stress-related response is needed. Nonetheless, the apoptotic immunosuppression by dexamethasone is attributable to its severe cytotoxicity. J. Cell. Physiol. 223:679–686, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background: A reliable temporary vascular access is always required for hemodialysis when a permanent vascular access is not available. However, techniques for creating temporary vascular accesses remain imperfect. This study utilized the ‘SiteRite’ ultrasound device to improve both success and complication rates of jugular venous cannulation for temporary access. Methods: This prospective, comparative study recruited 104 uremic patients receiving ultrasound-guided and 86 patients undergoing landmark-guided percutaneous internal jugular venous cannulation of dual-lumen dialysis catheters. Success rate, number of puncture attempts, access time, and the complication rate of the ultrasound technique, in comparison with the landmark-guided technique, were studied. Results: The ultrasound-guided cannulation was superior to the external landmark-guided cannulation in overall success rate (99.0 vs. 86.0%, p < 0.01), success rate of the first puncture attempt (80.8 vs. 34.9%, p < 0.01), average puncture (access) times (15.8 vs. 43.7 s, p < 0.01), puncture trials (1.39 vs. 2.58, p < 0.01), and traumatic complication rate (1.9 vs. 11.6%, p = 0.015). The incidence of infective complications for the ultrasound group was not different from that of the landmark-guided groups (2.9 vs. 2.3%, p = 0.589). Conclusion: The ultrasound-guided technique offers both safety and convenience in inserting jugular venous dialysis catheters. It represents a valuable technique in creating temporary dialysis hemoaccesses. [ABSTRACT FROM AUTHOR]

Two cases of lipoprotein glomerulopathy with a new apolipoprotein E (Apo E) genotype, ε3/ε4, were diagnosed recently. These 2 cases, together with other cases documented in English literature made a total of 6 common isoforms of Apo E encountered in lipoprotein glomerulopathy. Although the calculated allele frequency of ε2 is relative high in cases with lipoprotein glomerulopathy as compared with that in the general population (39.3 vs. 6.4–11.4%), the gradual emergence of Apo E isoforms other than E2/E3 in lipoprotein glomerulopathy implicates that the genetic susceptibility of certain Apo E isoforms may not be a crucial factor. An alteration in the local environment of glomerular capillaries may be more important in the pathogenesis of lipoprotein glomerulopathy. [ABSTRACT FROM AUTHOR]

The article discusses the case of a 73-year-old man who developed giant pyohydronephrosis. It notes that the patient had been receiving regular haemodialysis via arteriovenous fistula. No evidence of vegetation was seen in echocardiography. Meanwhile, a giant left hydronephoris and hydroureter were revealed in the computed tomography of the abdomen. It cites the major causes of giant hydronephrosis including congenital ureteral narrowing and ureteropelvic tumours.