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. METHODS: We prospectively enrolled adult patients who were receiving hemodialysis through an arteriovenous access and who had a risk score ⩽3 (low-risk) or ⩾8 (high-risk). We compared the occurrence of access stenosis (>50% on ultrasonography or angiography) between low-risk and high-risk groups and assessed clinical monitoring results for each group. RESULTS: Of the 38 patients analyzed (18 low-risk; 20 high-risk), 16 (42%) had significant stenosis. Clinical monitoring results were positive in 39% of the low-risk and 60% of the high-risk group (p = 0.19). The high-risk group had significantly higher occurrence of stenosis than the low-risk group (65% vs 17%; p = 0.003). Sensitivity and specificity of a high score for identifying stenosis were 81% and 68%, respectively. The positive predictive value of a high-risk score was 65%, and the negative predictive value was 80%. Only 11 (58%) of 19 subjects with positive clinical monitoring had significant stenosis. In a multivariable model, the high-risk group had seven-fold higher odds of stenosis than the low-risk group (aOR = 7.38; 95% CI, 1.44-37.82; p = 0.02). Positive clinical monitoring results and previous stenotic history were not associated with stenosis. Every unit increase in the score was associated with 34% higher odds of stenosis (aOR = 1.34; 95% CI, 1.05-1.70; p = 0.02). CONCLUSIONS: A calculated risk score may help predict the development of hemodialysis vascular access stenosis and may provide a simple and reliable objective measure for risk stratification.

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. METHODS: Measurement of five factors over the preceding 28 days from 1.46 million hemodialysis treatments (6163 patients) were used to develop a score associated with interventions over the subsequent 60 days. The score was validated in a separate dataset of 298,620 treatments (2641 patients). RESULTS: Interventions in arteriovenous fistulae (AVF; n = 4125) were much more common in those with the highest score (36.2%) than in those with the lowest score (11.0). The score also was strongly associated with interventions in patients with an arteriovenous graft (AVG; n = 2,038; 43.2% vs. 21.1%). There was excellent agreement in the Validation datasets for AVF (OR = 2.67 comparing the highest to lowest score) and good agreement for AVG (OR = 1.92). CONCLUSIONS: This simple risk score based on surveillance data may be useful for prioritizing patients for physical examination and potentially early referral for intervention.

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. Patients were initially dosed thrice weekly; dose was titrated to achieve a hemoglobin level ≥11.0 g/dl, followed by titration for maintenance. The primary endpoints were change in hemoglobin (weeks 28-52) and proportion of patients achieving a hemoglobin response (hemoglobin ≥11.0 g/dl and increase ≥1.0 g/dl [baseline >8.0 g/dl], or increase ≥2.0 g/dl [baseline ≤8.0 g/dl]) (week 24). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were recorded. RESULTS: In roxadustat (n = 616) and placebo (n = 306) groups, hemoglobin mean (SD) change from baseline over weeks 28-52 was significantly larger for roxadustat (2.00 [0.95]) versus placebo (0.16 [0.90]), corresponding to least-squares mean difference of 1.85 g/dl (95% confidence interval [CI] 1.74-1.97; P < 0.0001). The proportion of patients achieving a response at week 24 was larger for roxadustat (86.0%; 95% CI 83.0%-88.7%) versus placebo (6.6%; 95% CI 4.1%-9.9%; P < 0.0001). The proportion of patients receiving rescue therapy at week 52 was smaller for roxadustat (8.9%) versus placebo (28.9%); hazard ratio, 0.19 (95% CI 0.14-0.28; P < .0001). The incidences of TEAEs and TESAEs were comparable. CONCLUSION: This study showed that roxadustat corrected and maintained hemoglobin and was well tolerated in patients with CKD-related anemia not on dialysis (ClinicalTrials.gov NCT01750190).

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) ≤10.0 g/dL. Primary endpoints were mean Hb (g/dL) change from baseline averaged over Weeks 28-52 regardless of rescue therapy [non-inferiority criterion: lower limit of 95% confidence interval (CI) for treatment difference >-0.75] and percentage of patients achieving an Hb response between Weeks 1 and 24 censored for rescue therapy (non-inferiority margin for between-group difference -15%). Adverse events were monitored. RESULTS: The intent-to-treat population included patients randomized to roxadustat (n = 522) or epoetin alfa (n = 521). Mean (standard deviation) Hb changes from baseline averaged over Weeks 28-52 were 2.57 (1.27) and 2.36 (1.21) in the roxadustat and epoetin alfa groups. Roxadustat was non-inferior [least squares mean difference: 0.18 (95% CI 0.08, 0.29)] to epoetin alfa. Percentages of patients with an Hb response were 88.2% and 84.4% in the roxadustat and epoetin alfa groups, respectively. Roxadustat was non-inferior to epoetin alfa [treatment-group difference 3.5% (95% CI -0.7%, 7.7%)]. Adverse event rates were comparable between treatment groups. CONCLUSIONS: Roxadustat was efficacious for correcting and maintaining Hb levels compared with epoetin alfa. Roxadustat had an acceptable safety profile.

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. It invokes changes in iron metabolism that are the exact opposite of those occurring during pure iron deficiency. As a result, transferrin saturation (TSAT) becomes a poorer index of iron availability to the bone marrow and serum ferritin no longer represents iron that can be used during erythropoiesis. We argue that serum iron may provide more information to guide iron therapy than TSAT. In other words, the emphasis on TSAT is misplaced. With the development of a number of hypoxia-inducible factor prolyl hydroxylase inhibitors, which restore iron metabolism toward the 'physiologic state', the iron indices indicating sufficient iron availability to avoid functional iron deficiency during therapy of CKD-associated anemia are likely to change. We summarize these changes in the section 'A peek into things to come!', citing the available data.

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. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The retrospective study included all vascular access procedures at one institution from March 2014 to June 2016. Data included demographics, comorbidities, vascular access features, %ΔVAPR = ((Pre-Post)/Pre] × 100% assessed within the first 2 weeks post-percutaneous transluminal balloon angioplasty, time-to-next procedure, and patency. The log-rank test compared the area under the curve, receiver operating curve, Kaplan-Meier arteriovenous graft and arteriovenous fistula survival curves. A multivariable Cox proportional hazard (CP) model was used to determine the association of %ΔVAPR with access patency. RESULTS: Analysis of 138 subjects (females 51%; Black 87%) included 64 arteriovenous fistulas with 104 angioplasties and 74 arteriovenous grafts with 134 angioplasties. The area under the receiver operating characteristic curve for fistula failure at 3 months was 0.59, with optimal screening characteristics of 33.3%, sensitivity of 56.1%, and specificity of 63.2%. Arteriovenous fistula with <33.3% decline compared to >33.3% required earlier subsequent procedure (136 vs 231 days), lower survival on Kaplan-Meier analysis (P = 0.01), and twofold greater risk of failure (P = .006). Area under the receiver operating characteristic for arteriovenous graft failure at 3 months had a sensitivity of 52.3% and specificity of 67.4%. Arteriovenous graft with a post-intervention vascular access pressure ratio decline of <28.8% also required earlier subsequent procedure (144 vs 189 days), lower survival on Kaplan-Meier (P = 0.04), and a 59% higher risk for failure. The area under the receiver operating characteristic curve for combined access failure (arteriovenous fistula + arteriovenous graft) at 3 months had an optimal cut-point value of 31.2%, a sensitivity of 54.6%, and a specificity of 63.1%. Access with a <31.2% drop had a 62% increase in the risk of failure (hazard ratio 1.62; confidence interval 1.16, 2.27; P = 0.005). CONCLUSION: The magnitude of post-intervention reduction in vascular access pressure ratio provides a novel predictive measure of access outcomes.

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. The National Institutes of Health consortium demonstrated the difficulty in attaining a functional AVF in hemodialysis patients. Recognition of flaws in AVF and the quest to reduce catheter use bring to the fore the benefits of arteriovenous grafts (AVG). Advances in catheter technologies, flow, care, and antibiotic locks have resulted in significant improvement in catheter-related infections. However, widespread recognition of catheter-related complications like central vein stenosis, metastatic infections, and exhaustion of venous access sites preclude their being a viable alternative to AVF, furthering the need to explore AVG as a substitute. Placement of "early cannulation" AVG is a catheter sparing option in patients who are likely to have inadequate fistula maturation. Advances in biohybrid technology and tissue-engineered grafts are providing a robust opportunity to develop biocompatible graft materials with minimal tissue reactivity and thrombogenicity. Xenografts (bovine carotid artery grafts) are proving to be comparable and, in many cases, better than conventional polytetrafluoroethylene material. Older age, dialysis dependence, and smaller vein size are related to the appropriateness of AVG creation. An individualized approach in selecting optimal upper extremity vascular access option using patient-specific factors while incorporating the benefits of an AVG would greatly aid in achieving low catheter usage in the dialysis population.

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 (1.1-1.75 mg/kg) or high (1.50-2.25 mg/kg) FG-4592 starting doses or to placebo. In the DD study, 87 were enrolled to low (1.1-1.8 mg/kg), medium (1.5-2.3 mg/kg) and high (1.7-2.3 mg/kg) starting FG-4592 doses or to continuation of epoetin alfa. In both studies, only oral iron supplementation was allowed. RESULTS: In the NDD study, hemoglobin (Hb) increase ≥1 g/dL from baseline was achieved in 80.0% of subjects in the low-dose cohort and 87.1% in the high-dose cohort, versus 23.3% in the placebo arm (P < 0.0001, both). In the DD study, 59.1%, 88.9% (P = 0.008) and 100% (P = 0.0003) of the low-, medium- and high-dose subjects maintained their Hb levels after 5- and 6-weeks versus 50% of the epoetin alfa-treated subjects. In both studies, significant reductions in cholesterol were noted in FG-4592-treated subjects, with stability or increases in serum iron, total iron-binding capacity (TIBC) and transferrin (without intravenous iron administration). In the NDD study, hepcidin levels were significantly reduced across all FG-4592-treated arms as compared with no change in the placebo arm. In the DD study, hepcidin levels were also reduced in a statistically significant dose-dependent manner in the highest dose group as compared with the epoetin alfa-treated group. Adverse events were similar for FG-4592-treated and control subjects. CONCLUSIONS: FG-4592 may prove an effective alternative for managing anemia of CKD. It is currently being investigated in a pivotal global Phase 3 program.

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. Treatment duration was 16 or 24 weeks. Intravenous iron was prohibited. The primary end point was the proportion of patients achieving hemoglobin increase of ≥1.0 g/dl from baseline and hemoglobin of ≥11.0 g/dl by week 17 (16 weeks of treatment). Secondary analyses included mean hemoglobin change from baseline, iron utilization, and serum lipids. Safety was evaluated by frequency/severity of adverse events. RESULTS: Of the 145 patients enrolled, 143 were evaluable for efficacy. Overall, 92% of patients achieved hemoglobin response. Higher compared with lower starting doses led to earlier achievement of hemoglobin response. Roxadustat-induced hemoglobin increases were independent of baseline C-reactive protein levels and iron repletion status. Overall, over the first 16 treatment weeks, hepcidin levels decreased by 16.9% (P=0.004), reticulocyte hemoglobin content was maintained, and hemoglobin increased by a mean (±SD) of 1.83 (±0.09) g/dl (P<0.001). Overall mean total cholesterol level was reduced by a mean (±SD) of 26 (±30) mg/dl (P<0.001) after 8 weeks of therapy, independent of the use of statins or other lipid-lowering agents. No drug-related serious adverse events were reported. CONCLUSIONS: In patients with nondialysis CKD who were anemic, various starting dose regimens of roxadustat were well tolerated and achieved anemia correction with reduced serum hepcidin levels. After anemia correction, hemoglobin was maintained by roxadustat at various dose frequencies without intravenous iron supplementation.

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. INTERVENTION: Part 1: 6-week dose-ranging study in 54 individuals of thrice-weekly oral roxadustat doses versus continuation of intravenous epoetin alfa. Part 2: 19-week treatment in 90 individuals in 6 cohorts with various starting doses and adjustment rules (1.0-2.0mg/kg or tiered weight based) in individuals with a range of epoetin alfa responsiveness. Intravenous iron was prohibited. OUTCOMES: Primary end point was Hb level response, defined as end-of-treatment Hb level change (ΔHb) of -0.5g/dL or greater from baseline (part 1) and as mean Hb level ≥ 11.0g/dL during the last 4 treatment weeks (part 2). MEASUREMENTS: Hepcidin, iron parameters, cholesterol, and plasma erythropoietin (the latter in a subset). RESULTS: Baseline epoetin alfa doses were 138.3±51.3 (SD) and 136.3±47.7U/kg/wk in part 1 and 152.8±80.6 and 173.4±83.7U/kg/wk in part 2, in individuals randomly assigned to roxadustat and epoetin alfa, respectively. Hb level responder rates in part 1 were 79% in pooled roxadustat 1.5 to 2.0mg/kg compared to 33% in the epoetin alfa control arm (P=0.03). Hepcidin level reduction was greater at roxadustat 2.0mg/kg versus epoetin alfa (P<0.05). In part 2, the average roxadustat dose requirement for Hb level maintenance was ∼1.7mg/kg. The least-squares-mean ΔHb in roxadustat-treated individuals was comparable to that in epoetin alfa-treated individuals (about -0.5g/dL) and the least-squares-mean difference in ΔHb between both treatment arms was -0.03 (95% CI, -0.39 to 0.33) g/dL (mixed effect model-repeated measure). Roxadustat significantly reduced mean total cholesterol levels, not observed with epoetin alfa. No safety concerns were raised. LIMITATIONS: Short treatment duration and small sample size. CONCLUSIONS: In this phase 2 study of anemia therapy in patients with end-stage renal disease on maintenance hemodialysis therapy, roxadustat was well tolerated and effectively maintained Hb levels.

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≤10.0 g/dl) patients incident to hemodialysis (HD) or peritoneal dialysis (PD). Sixty patients received no iron, oral iron, or IV iron while treated with roxadustat for 12 weeks. Mean±SD baseline Hb was 8.3±1.0 g/dl in enrolled patients. Roxadustat at titrated doses increased mean Hb by ≥2.0 g/dl within 7 weeks regardless of baseline iron repletion status, C-reactive protein level, iron regimen, or dialysis modality. Mean±SEM maximal change in Hb from baseline (ΔHb(max)), the primary endpoint, was 3.1±0.2 g/dl over 12 weeks in efficacy-evaluable patients (n=55). In groups receiving oral or IV iron, ΔHb(max) was similar and larger than in the no-iron group. Hb response (increase in Hb of ≥1.0 g/dl from baseline) was achieved in 96% of efficacy-evaluable patients. Mean serum hepcidin decreased significantly 4 weeks into study: by 80% in HD patients receiving no iron (n=22), 52% in HD and PD patients receiving oral iron (n=21), and 41% in HD patients receiving IV iron (n=9). In summary, roxadustat was well tolerated and corrected anemia in incident HD and PD patients, regardless of baseline iron repletion status or C-reactive protein level and with oral or IV iron supplementation; it also reduced serum hepcidin levels.

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) ≤11.0 g/dL were sequentially enrolled into four dose cohorts and randomized to roxadustat or placebo two times weekly (BIW) or three times weekly (TIW) for 4 weeks, in an approximate roxadustat:placebo ratio of 3:1. Efficacy was assessed by (i) mean Hb change (ΔHb) from baseline (BL) and (ii) proportion of Hb responders (ΔHb ≥ 1.0 g/dL). Pharmacodynamic evaluation was performed in a subset of subjects. Safety was evaluated by adverse event frequency/severity. RESULTS: Of 116 subjects receiving treatment, 104 completed 4 weeks of dosing and 96 were evaluable for efficacy. BL characteristics for roxadustat and placebo groups were comparable. In roxadustat-treated subjects, Hb levels increased from BL in a dose-related manner in the 0.7, 1.0, 1.5 and 2.0 mg/kg groups. Maximum ΔHb within the first 6 weeks was significantly higher in the 1.5 and 2.0 mg/kg groups than in the placebo subjects. Hb responder rates were dose dependent and ranged from 30% in the 0.7 mg/kg BIW group to 100% in the 2.0 mg/kg BIW and TIW groups versus 13% in placebo. CONCLUSIONS: Roxadustat transiently and moderately increased endogenous erythropoietin and reduced hepcidin. Adverse events were similar in the roxadustat and placebo groups. Roxadustat produced dose-dependent increases in blood Hb among anemic NDD-CKD patients in a placebo-controlled trial. CLINICAL TRIALS REGISTRATION: Clintrials.gov #NCT00761657.

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. The FPC group received dialysate containing 2 µmol/l of iron. The placebo group received standard dialysate. A blinded central anemia management group facilitated ESA dose adjustments. Intravenous iron was administered according to the approved indication when ferritin levels fell below 200 µg/l. The primary end point was the percentage change from baseline in prescribed ESA dose at end of treatment. Secondary end points included intravenous iron use and safety. At the end of treatment, there was a significant 35% reduction in prescribed ESA dose in FPC-treated patients compared with placebo. The FPC patients used 51% less intravenous iron than placebo. Adverse and serious adverse events were similar in both groups. Thus, FPC delivered via dialysate significantly reduces the prescribed ESA dose and the amount of intravenous iron needed to maintain hemoglobin in chronic hemodialysis patients.

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. The primary end-point was change in platelet count 60 days post infusion of LMWID in those with and without concomitant darbepoetin administration. Secondary end-points were the correlations between changes in platelet count and iron indices. RESULTS: A total of 108 patients met inclusion and exclusion criteria. The decrease in platelet counts in response to iron repletion was statistically significant (305.72 ± 108.86 vs 255.58 ± 78.97, P = < .0001). The decrease in platelet count was independent of concomitant darbepoetin use. Bivariate regression analysis between baseline platelet count and transferrin saturation by iron (TSAT) showed a negative association (ßTSAT = -5.82, P = .0007) and moderate correlation (R = 0.32). Following iron treatment, the within individual changes in platelet count in 60 days were not related to changes in TSAT (ßΔTSAT = -0.41, P = .399) and demonstrated a poor correlation (R = 0.10). CONCLUSIONS: Parenteral iron treatment by LMWID is associated with reduction in platelet counts in iron deficient anemic ND-CKD patients. However, ESA use in the majority of patients prior to intravenous iron administration could have altered platelet production through bone marrow competition.

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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This prospective, multicenter, observational cohort study compared the effectiveness of two catheter locking solutions (gentamicin/citrate versus heparin) in 555 hemodialysis patients dialyzing with a tunneled cuffed catheter between 2008 and 2011. The groups were not mutually exclusive. Rates of catheter-related bloodstream infection and mortality hazards were compared between groups. RESULTS: The study population (n=555 and 1350 catheters) had a median age of 62 years (interquartile range=41-83 years), with 50% men and 71% black. There were 427 patients evaluable in the heparin period (84,326 days) and 322 patients evaluable in the antibiotic lock period (71,192 days). Catheter-related bloodstream infection in the antibiotic lock period (0.45/1000 catheter days) was 73% lower than the heparin period (1.68/1000 catheter days; P=0.001). Antibiotic lock use was associated with a decreased risk of catheter-related bloodstream infection compared with heparin (risk ratio, 0.23; 95% confidence interval, 0.13 to 0.38 after multivariate adjustment). Cox proportional hazards modeling found that antibiotic lock was associated with a reduction in mortality (hazard ratio, 0.36; 95% confidence interval, 0.22 to 0.58 in unadjusted analyses; hazard ratio, 0.32; 95% confidence interval, 0.14 to 0.75 after multivariate adjustment). The rate of gentamicin-resistant organisms decreased (0.40/1000 person-years to 0.22/1000 person-years) in the antibiotic lock period (P=0.01). CONCLUSIONS: The results of this study show that the use of a prophylactic, gentamicin/citrate lock was associated with a substantial reduction in catheter-related bloodstream infection and is the first to report a survival advantage of antibiotic lock in a population at high risk of infection-related morbidity 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. Efficacy data was obtained by retrospective chart review of 150 consecutively enrolled patients. Patients were assigned per protocol to oral or IV iron, with IV iron given to those with lower iron stores and/or hemoglobin. Iron and darbepoetin were administered to achieve and maintain hemoglobin at 10-12 g/dL. Efficacy endpoints were mean hemoglobin and change in iron indices approximately 30 and 60 days after enrollment. Safety data was obtained by retrospective review of reported adverse drug events (ADEs) following 1699 infusions of LMWID (0.5-1.0 g). Results. Mean hemoglobin, iron saturation, and ferritin increased significantly from baseline to 60 days in patients assigned to LMWID (hemoglobin: 11.3 versus 9.4 g/dL; iron saturation: 24% versus 12.9%; ferritin: 294.7 versus 134.7 ng/mL; all P values < 0.0001). Iron stores and hemoglobin were maintained in the group assigned to oral iron. Of 1699 iron dextran infusions, three ADEs occurred. Conclusions. Treatment of anemia in CKD stages 3 and 4 with LMWID and darbepoetin is efficacious. The serious ADE rate was 0.06% per infusion.