Hemodialysis Vascular Access: A Historical Perspective on Access Promotion, Barriers, and Lessons for the Future.

This review describes the history of vascular access for hemodialysis (HD) over the past 8 decades. Reliable, repeatable vascular access for outpatient HD began in the 1960s with the Quinton-Scribner shunt. This was followed by the autologous Brecia-Cimino radial-cephalic arteriovenous fistula (AVF), which dominated HD vascular access for the next 20 years.

Association of risk stratification score with dialysis vascular access stenosis.

Backgrounds: Clinical monitoring is the recommended standard for identifying dialysis access dysfunction; however, clinical monitoring requires skill and training, which is challenging for understaffed clinics and overburdened healthcare personnel. A vascular access risk stratification score was recently proposed to assist in detecting dialysis access dysfunction.

Purpose: Our objective was to evaluate the utility of using vascular access risk scores to assess venous stenosis in hemodialysis vascular accesses.

Development and validation of a risk score to prioritize patients for evaluation of access stenosis.

Background: Access flow dysfunction, often associated with stenosis, is a common problem in hemodialysis access and may result in progression to thrombosis. Timely identification of accesses in need of evaluation is critical to preserving a functioning access. We hypothesized that a risk score using measurements obtained from the Vasc-Alert surveillance device could be used to predict subsequent interventions.

Roxadustat for CKD-related Anemia in Non-dialysis Patients.

Introduction: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and improves iron metabolism. We assessed the efficacy and tolerability of roxadustat in patients with chronic kidney disease (CKD)-related anemia not on dialysis.

Methods: ANDES was a global Phase 3 randomized study in which adults with stage 3-5 CKD not on dialysis received roxadustat or placebo.

Roxadustat for anemia in patients with end-stage renal disease incident to dialysis.

Background: We evaluated the efficacy and safety of roxadustat versus epoetin alfa for the treatment of chronic kidney disease-related anemia in patients new to dialysis.

Methods: HIMALAYAS was a Phase 3, open-label, epoetin alfa-controlled trial. Eligible adults were incident to hemodialysis/peritoneal dialysis for 2 weeks to ≤4 months prior to randomization and had mean hemoglobin (Hb) ≤10.

The problem with transferrin saturation as an indicator of iron 'sufficiency' in chronic kidney disease.

After a brief review of physiological iron metabolism, we describe diagnostic tests for iron status and iron deficiency anemia in patients without chronic kidney disease (CKD) or inflammation. Thereafter we review the dysregulation of iron metabolism in CKD. Specific emphasis is placed on the role of the 'inflammatory' state that develops with the progression of CKD.

Sentinel vascular access monitoring after endovascular intervention predicts access outcome.

Background And Objectives: The vascular access pressure ratio test identifies dialysis vascular access dysfunction when three consecutive vascular access pressure ratios are >0.55. We tested whether the magnitude of the decline in vascular access pressure ratio 1-week post-intervention could alert of subsequent access failure.

How arteriovenous grafts could help to optimize vascular access management.

A one-size-fits-all approach to vascular access for dialysis may be prejudicial. Arteriovenous fistulae (AVF) have high primary failure, failure to mature rate, and late-stage complications making them unsuitable choice for many patients. Aging of population with chronic kidney disease (CKD) coupled with venous injury during CKD stages depletes suitable superficial veins for AVF creation.

Characteristics of enzyme-linked immunosorbent assay for detection of IgG antibodies specific to Сhlamydia trachomatis heat shock protein (HSP-60).

The goal of this work was to study sensitivity and specificity of the developed ELISA set for the identification of IgG antibodies against Chlamydia trachomatis HSP-60 (using biotinylated tyramine-based signal amplification system). The study was conducted using a panel of characterized sera, as well as two reference ELISA sets of similar purpose. According to the results of ELISA informative value parameters, the ELISA we have developed showed the highest specificity and sensitivity parameters (no false negative or false positive results were registered).

Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China.

Background: FG-4592 (roxadustat) is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (HIF-PHI) promoting coordinated erythropoiesis through the transcription factor HIF. Two Phase 2 studies were conducted in China to explore the safety and efficacy of FG-4592 (USAN name: roxadustat, CDAN name: ), a HIF-PHI, in patients with anemia of chronic kidney disease (CKD), both patients who were dialysis-dependent (DD) and patients who were not dialysis-dependent (NDD).

Methods: In the NDD study, 91 participants were randomized to low (1.

Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD.

Background And Objectives: Roxadustat (FG-4592), an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis, regulates iron metabolism, and reduces hepcidin, was evaluated in this phase 2b study for safety, efficacy, optimal dose, and dose frequency in patients with nondialysis CKD.

Design, Setting, Participants, & Measurements: The 145 patients with nondialysis CKD and hemoglobin ≤10.5 g/dl were randomized into one of six cohorts of approximately 24 patients each with varying roxadustat starting doses (tiered weight and fixed amounts) and frequencies (two and three times weekly) followed by hemoglobin maintenance with roxadustat one to three times weekly.

Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study.

Background: Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin.

Study Design: Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study.

Setting & Participants: Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with epoetin alfa.

Roxadustat (FG-4592): Correction of Anemia in Incident Dialysis Patients.

Safety concerns with erythropoietin analogues and intravenous (IV) iron for treatment of anemia in CKD necessitate development of safer therapies. Roxadustat (FG-4592) is an orally bioavailable hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that promotes coordinated erythropoiesis through HIF-mediated transcription. We performed an open-label, randomized hemoglobin (Hb) correction study in anemic (Hb≤10.

Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients.

Background: Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis. This Phase 2a study tested efficacy (Hb response) and safety of roxadustat in anemic nondialysis-dependent chronic kidney disease (NDD-CKD) subjects.

Methods: NDD-CKD subjects with hemoglobin (Hb) ≤11.

Ferric pyrophosphate citrate administered via dialysate reduces erythropoiesis-stimulating agent use and maintains hemoglobin in hemodialysis patients.

Ferric pyrophosphate citrate (FPC) is a water-soluble iron salt administered via dialysate to supply iron directly to transferrin. The PRIME study tested whether treatment with FPC could reduce prescribed erythropoiesis-stimulating agent (ESA) use and maintain hemoglobin in hemodialysis patients. This 9-month, randomized, placebo-controlled, double-blind, multicenter clinical study included 103 patients undergoing hemodialysis 3-4 times weekly.

Vascular access cannulation practices and outcomes.

Vascular access cannulation practices such as the dialysis prescription for blood pump flow and dialysis duration vary significantly among countries. Choice of needle gauge and cannulation practice with the needle in terms of direction relative to the flow stream and rotation after insertion are dictated in part by practicalities but appear to be mostly the result of 'cultural' practices within dialysis centers. Prospective studies of cannulation are needed to improve access outcomes.

Iron repletion is associated with reduction in platelet counts in non-dialysis chronic kidney disease patients independent of erythropoiesis-stimulating agent use: a retrospective cohort study.

Background: Iron deficiency is common in non-dialysis chronic kidney disease (ND-CKD) patients and, on occasion, requires parenteral iron therapy. We investigated the effect of intravenous iron repletion on platelet counts in ND-CKD patients with and without concomitant darbepoetin administration.

Methods: We conducted a retrospective analysis of ND-CKD patients with iron deficiency anemia treated with low molecular weight iron dextran (LMWID) between 2005 and 2009 at our CKD clinic.

Comparative effectiveness of two catheter locking solutions to reduce catheter-related bloodstream infection in hemodialysis patients.

Background And Objectives: Infection is the second leading cause of death in hemodialysis patients. Catheter-related bloodstream infection and infection-related mortality have not improved in this population over the past two decades. This study evaluated the impact of a prophylactic antibiotic lock solution on the incidence of catheter-related bloodstream infection and mortality.

Intravenous iron dextran as a component of anemia management in chronic kidney disease: a report of safety and efficacy.

Objective. We aimed to demonstrate safety and efficacy of intravenous (IV) low molecular weight iron dextran (LMWID) during treatment of anemic stage 3 and 4 chronic kidney disease (CKD) patients. Methods.

Peginesatide in patients with anemia undergoing hemodialysis.

Background: Peginesatide, a synthetic peptide-based erythropoiesis-stimulating agent (ESA), is a potential therapy for anemia in patients with advanced chronic kidney disease.

Methods: We conducted two randomized, controlled, open-label studies (EMERALD 1 and EMERALD 2) involving patients undergoing hemodialysis. Cardiovascular safety was evaluated by analysis of an adjudicated composite safety end point--death from any cause, stroke, myocardial infarction, or serious adverse events of congestive heart failure, unstable angina, or arrhythmia--with the use of pooled data from the two EMERALD studies and two studies involving patients not undergoing dialysis.

An open-label, sequential, dose-finding study of peginesatide for the maintenance treatment of anemia in chronic hemodialysis patients.

Background: Peginesatide is a peptide-based erythropoiesis-stimulating agent that was designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. The primary objective of this phase 2 dose-finding study was to determine the once-monthly peginesatide dosing strategy that would maintain hemoglobin within ±1.0 g/dL of baseline values after conversion from epoetin alfa; the safety of peginesatide was evaluated concurrently.