CRP AND ATHEROSCLEROSIS IN HEMODIALYSIS PATIENTS, A NESTED CROSS-SECTIONAL STUDY

CRP is a recognized marker of systemic inflammation. The degree to which CRP is associated with carotid and/or femoral intima media thickness (IMT), markers of atherosclerosis, may quantify the degree to which inflammation explains cardiovascular disease in patients with end stage renal disease. The purpose of this study was to estimate the association between CRP and both carotid and femoral IMT in hemodialysis (HD) patients. The present cross-sectional study is nested in the Sevelamer hydrochloride and ultrasound-measured femoral and carotid intima media thickness progression in end stage renal disease (SUMMER) clinical trial. Carotid (common, internal and bifurcation) and femoral arteries were visualized in B-mode ultrasonography. CRP was measured in serum. The study cohort included 177 HD patients (39.5% female, mean age 67.8±11.5 years). All measures of both carotid and femoral IMT were significantly, positively associated with CRP. Compared to subjects without, subjects with PVD, coronary revascularization and hypertension had significantly higher CRP levels. Conversely, subjects treated with sevelamer hydrochloride had significantly lower CRP levels than those not exposed to this medication. CRP was significantly, positively associated with serum phosphorus, calcium and PTH, and significantly inversely associated with HDL. In conclusion, CRP is significantly, positively associated with both femoral and carotid IMT and suggests an association between inflammation and atherosclerosis in HD patients

towards harmonization and excellence in training

Nephrology is a young medical specialty that has evolved and expanded during the last 4 decades of the past century, becoming recognized as one of the most innovative and challenging medical specialties. The training of nephrology takes place mainly in public hospitals, and there are important variations in the duration and assessment of training among the European countries. The Union of European Medical Specialties (UEMS) Renal Section and the European Renal Association- European Dialysis and Transplant Association have been working jointly since 2010 to harmonize European nephrology training and more recently to establish the European Certificate in Nephrology (ECN). The first two editions of the ECN were held in early 2017 and 2018. In total, 122 candidates from 26 countries have sat for the exam, with a success rate of 59% (72/ 122). To date, Switzerland has adopted the exam as their national training assessment and we expect that other countries will join Switzerland in the near future. Fostering the development and importance of the ECN requires that member states work to increase the academic and professional profile of the ECN within their countries. The ECN should be considered a 'quality mark' and a sign of high achievement in nephrology training in Europe. If holding the ECN becomes advantageous for employment or improving scientific careers, the number of candidates will increase and the sustainability of the ECN will be guaranteed. A recent, positive development is the pre-agreement between the UEMS Renal Section, UK Renal Association and Royal Colleges of the UK to adopt a unique pan-European exam beginning in 2020. However, any decision to commence the pan-European exam will depend, in part, on strong candidate enrolment for the ECN 2019 edition. Thus support of the national societies is crucial for the sustainability and growth of a European exam, because of their capacities to influence strategic policies in hospitals, universities and medical associations, with a longer-term aim to increase the professional recognition of the European exam.publishersversionpublishe

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Status of Nutrition in Hemodialysis Patients Survey (SNIPS): Nutrition Intake in Obese and Overweight vs. Healthy Weight Patients

Elevated body mass index (BMI) has been associated with improved survival and fewer hospitalizations in hemodialysis patients; however, it is not clear that dietary intake is associated with increased BMI in hemodialysis patients. The present analysis was designed to compare energy and macronutrient intake and distribution, as well as compliance with the International Society of Renal Nutrition and Metabolism (ISRNM) dietary guidelines, by body weight status (overweight/obese vs. normal weight) in hemodialysis patients. The status of nutrition in hemodialysis patients survey (SNIPS) cohort is a cross-sectional study including a representative sample of individuals on hemodialysis treated in hospital dialysis centers throughout Israel. Of the 375 patients eligible for the current analysis, 60.1% had BMI ≥ 25 kg/m2 (overweight/obese). For each participant, the following measures were recorded: dietary intake, blood biochemistry, anthropometric and hemodynamic measures. These were compared by body weight status. Compared to their normal-weight counterparts, overweight/obese hemodialysis patients did not differ by energy and macronutrient intake, distribution of these nutrients in the diet. Regardless of body weight status, hemodialysis patients have poor compliance with ISRNM dietary guidelines

Care of undocumented-uninsured immigrants in a large urban dialysis unit

Abstract Background: Medical, ethical and financial dilemmas may arise in treating undocumented-uninsured patients with end-stage renal disease (ESRD). Hereby we describe the 10-year experience of treating undocumented-uninsured ESRD patients in a large public dialysis-unit

Vascular Endothelial Growth Factor Augments Arginine Transport and Nitric Oxide Generation via a KDR Receptor Signaling Pathway

Background/Aims: Vascular endothelial growth factor (VEGF) is an endothelium-specific peptide that stimulates angiogenesis via two receptor tyrosine kinases, Flt-1 and KDR. Endothelial nitric oxide synthase (eNOS) plays a major role in VEGF signaling. Delivery of arginine to membrane bound eNOS by the cationic amino acid transporter-1 (CAT-1) has been shown to modulate eNOS activity. The current studies were designed to test the hypothesis that VEGF enhances eNOS activity via modulation of arginine transport by CAT-1. Methods: Using radio-labeled arginine, {[3H] L-arginine} uptake was determined in human umbilical vein endothelial cells (HUVEC) following incubation with VEGF with and without silencing the VEGF receptors Flt-1 or KDR. Subsequently, western blotting for CAT-1, PKCα, ERK 1/2, JNK, and their phosphorylated forms were performed. NO generation was measured by the Griess reaction. Results: VEGF (50 and 100 ng/ml) significantly augmented endothelial arginine transport in a time dependent manner, an effect which was prevented by Sunitinib (2 µM), a multi targeted receptor tyrosine kinase inhibitor. The increase in arginine transport velocities by VEGF was not affected by silencing Flt-1 while silencing KDR abrogated VEGF effect. Furthermore, incubating cells with 50 and 100 ng of VEGF for 30 minutes significantly augmented CAT-1 abundance. The expression of PKC-α, JNK, and ERK1/2 and their phosphorylated forms were unchanged following incubation of HUVEC with VEGF. The concentration of NO2/NO3 following incubation with VEGF was significantly higher than from untreated cells. This increase was significantly attenuated by silencing KDR. Conclusions: VEGF increases arginine transport via modulation of CAT-1 in endothelial cells. This effect is exclusively dependent on KDR rather than Flt-1

Elevated urine heparanase levels are associated with proteinuria and decreased renal allograft function.

Heparanase is an endo-β-glucuronidase that cleaves heparan sulfate side chains, leading to structural modifications that loosen the extracellular matrix barrier and associated with tumor metastasis, inflammation and angiogenesis. In addition, the highly sulfated heparan sulfate proteoglycans are important constituents of the glomerular basement membrane and its permselective properties. Recent studies suggest a role for heparanase in several experimental and human glomerular diseases associated with proteinuria such as diabetes, minimal change disease, and membranous nephropathy. Here, we quantified blood and urine heparanase levels in renal transplant recipients and patients with chronic kidney disease (CKD), and assessed whether alterations in heparanase levels correlate with proteinuria and renal function. We report that in transplanted patients, urinary heparanase was markedly elevated, inversely associated with estimated glomerular filtration rate (eGFR), suggesting a relationship between heparanase and graft function. In CKD patients, urinary heparanase was markedly elevated and associated with proteinuria, but not with eGFR. In addition, urinary heparanase correlated significantly with plasma heparanase in transplanted patients. Such a systemic spread of heparanase may lead to damage of cells and tissues alongside the kidney.The newly described association between heparanase, proteinuria and decreased renal function is expected to pave the way for new therapeutic options aimed at attenuating chronic renal allograft nephropathy, leading to improved graft survival and patient outcome