Combination Treatment with Sodium Nitrite and Isoquercetin on Endothelial Dysfunction among Patients with CKD: A Randomized Phase 2 Pilot Trial.

BACKGROUND AND OBJECTIVES: Endothelial dysfunction is common among patients with CKD. We tested the efficacy and safety of combination treatment with sodium nitrite and isoquercetin on biomarkers of endothelial dysfunction in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This randomized, double-blind, placebo-controlled phase 2 pilot trial enrolled 70 patients with predialysis CKD. Thirty-five were randomly assigned to combination treatment with sodium nitrite (40 mg twice daily) and isoquercetin (225 mg once daily) for 12 weeks, and 35 were randomly assigned to placebo. The primary outcome was mean change in flow-mediated vasodilation over the 12-week intervention. Secondary and safety outcomes included biomarkers of endothelial dysfunction, inflammation, and oxidative stress as well as kidney function, methemoglobin, and adverse events. Intention-to-treat analysis was conducted. RESULTS: Baseline characteristics, including age, sex, race, cigarette smoking, history of hypertension and diabetes, use of renin-angiotensin system blockers, BP, fasting glucose, lipid profile, kidney function, urine albumin-creatinine ratio, and endothelial biomarkers, were comparable between groups. Over the 12-week intervention, flow-mediated vasodilation increased 1.1% (95% confidence interval, -0.1 to 2.3) in the treatment group and 0.3% (95% confidence interval, -0.9 to 1.5) in the placebo group, and net change was 0.8% (95% confidence interval, -0.9 to 2.5). In addition, changes in biomarkers of endothelial dysfunction (vascular adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, vWf, endostatin, and asymmetric dimethylarginine), inflammation (TNF-α, IL-6, C-reactive protein, IL-1 receptor antagonist, and monocyte chemoattractant protein-1), and oxidative stress (oxidized LDL and nitrotyrosines) were not significantly different between the two groups. Furthermore, changes in eGFR, urine albumin-creatinine ratio, methemoglobin, and adverse events were not significantly different between groups. CONCLUSIONS: This randomized phase 2 pilot trial suggests that combination treatment with sodium nitrite and isoquercetin did not significantly improve flow-mediated vasodilation or other endothelial function biomarkers but also did not increase adverse events compared with placebo among patients with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Nitrite, Isoquercetin, and Endothelial Dysfunction (NICE), NCT02552888.

Pseudohyperkalemia: Look before you treat.

Pseudohyperkalemia is defined as a reported rise in serum potassium concentration along with a normal effective plasma potassium concentration. We present a case report of a 57-year-old gentleman with a history of chronic lymphocytic leukemia, who presented with an elevation in serum potassium along with a normal plasma potassium concentration. Through an exploration of the literature, we demonstrate that pseudohyperkalemia is an important phenomenon to watch for as it may sometimes lead to unnecessary and potentially dangerous treatment.

Prevalence and Prognostic Significance of Apparent Treatment Resistant Hypertension in Chronic Kidney Disease: Report From the Chronic Renal Insufficiency Cohort Study.

The association between apparent treatment resistant hypertension (ATRH) and clinical outcomes is not well studied in chronic kidney disease. We analyzed data on 3367 hypertensive participants in the Chronic Renal Insufficiency Cohort (CRIC) to determine prevalence, associations, and clinical outcomes of ATRH in nondialysis chronic kidney disease patients. ATRH was defined as blood pressure ≥140/90 mm Hg on ≥3 antihypertensives, or use of ≥4 antihypertensives with blood pressure at goal at baseline visit. Prevalence of ATRH was 40.4%. Older age, male sex, black race, diabetes mellitus, and higher body mass index were independently associated with higher odds of having ATRH. Participants with ATRH had a higher risk of clinical events than participants without ATRH-composite of myocardial infarction, stroke, peripheral arterial disease, congestive heart failure (CHF), and all-cause mortality (hazard ratio [95% confidence interval], 1.38 [1.22-1.56]); renal events (1.28 [1.11-1.46]); CHF (1.66 [1.38-2.00]); and all-cause mortality (1.24 [1.06-1.45]). The subset of participants with ATRH and blood pressure at goal on ≥4 medications also had higher risk for composite of myocardial infarction, stroke, peripheral arterial disease, CHF, and all-cause mortality (hazard ratio [95% confidence interval], (1.30 [1.12-1.51]) and CHF (1.59 [1.28-1.99]) than those without ATRH. ATRH was associated with significantly higher risk for CHF and renal events only among those with estimated glomerular filtration rate ≥30 mL/min per 1.73 m(2). Our findings show that ATRH is common and associated with high risk of adverse outcomes in a cohort of patients with chronic kidney disease. This underscores the need for early identification and management of patients with ATRH and chronic kidney disease.

Comparison of Cutting Balloon Angioplasty and Percutaneous Balloon Angioplasty of Arteriovenous Fistula Stenosis: A Meta-Analysis and Systematic Review of Randomized Clinical Trials.

BACKGROUND: Hemodialysis (HD) access failure is a common cause of increased morbidity and healthcare cost in patients with end stage renal disease (ESRD). Percutaneous balloon angioplasty has been used to treat hemodialysis access stenosis but is complicated by a high rate of restenosis. Percutaneous cutting balloon (PCB) angioplasty is an alternative approach that has shown to reduce restenosis. OBJECTIVES: The aim of the study is to assess the safety and efficacy of PCB angioplasty in comparison with conventional and high-pressure balloon angioplasty in the treatment of hemodialysis access site stenosis. METHODS: We searched PubMed, EMBASE and the Cochrane Central register of controlled trials (CENTRAL) databases through August 2014 and selected studies using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. We included all randomized clinical trials with a head-to-head comparison between PCB and conventional or high-pressure balloon angioplasty RESULTS: Three studies with 1034 participants (age 60.7 (±12.9) years and 50.1% males) with 525 in PCB and 509 in control arm were included in the analysis. The immediate procedural success rate was not significantly different in the PCB angioplasty and control arm respectively, (87.2% vs. 83.7% RD -0.02; 95%CI -0.06 to 0.01; P = 0.38). The six-month target lesion patency was significantly higher in the PCB angioplasty arm (67.2% vs. 55.6% RD 0.12; 95%CI 0.05-0.19; P < 0.05) with number needed to treat (NNT) of 9. The device related complications were not statistically significant between groups (RD 0.03; 95%CI -0.02 to 0.07; P = 0.26). CONCLUSIONS: PCB angioplasty is effective in treatment of hemodialysis access stenosis, with significantly higher six-month patency compared to balloon angioplasty.