Net Budgetary Impact of Ferric Citrate as a First-Line Phosphate Binder for the Treatment of Hyperphosphatemia: A Markov Microsimulation Model.

Ferric citrate (FC) has demonstrated efficacy as a phosphate binder and reduces the requirements for erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron in dialysis patients. We developed a net budgetary impact model to evaluate FC vs. other phosphate binders from the vantage of a large dialysis provider. We used a Markov microsimulation model to simulate mutually referential longitudinal effects between serum phosphate and phosphate binder dose; categories of these defined health states. Health states probabilistically determined treatment attendance and utilization of ESA and IV iron. We derived model inputs from a retrospective analysis of incident phosphate binder users from a large dialysis organization (January 2011-June 2013) and incorporated treatment effects of FC from a phase III trial. The model was run over a 1-year time horizon. We considered fixed costs of providing dialysis; costs of administering ESA and IV iron; and payment rates for dialysis, ESAs, and IV iron. In the base-case model, FC had a net budgetary impact (savings) of +US$213,223/year per 100 patients treated vs. standard of care. One-way sensitivity analyses showed a net budgetary impact of up to +US$316,296/year per 100 patients treated when higher hemoglobin levels observed with FC translated into a 30% additional ESA dose reduction, and up to +US$223,281/year per 100 patients treated when effects on missed treatment rates were varied. Two-way sensitivity analyses in which acquisition costs for ESA and IV iron were varied showed a net budgetary impact of +US$104,840 to +US$213,223/year per 100 patients treated. FC as a first-line phosphate binder would likely yield substantive savings vs. standard of care under current reimbursement.

Characterization of chronic and acute ESA hyporesponse: a retrospective cohort study of hemodialysis patients.

BACKGROUND: Some patients with chronic kidney disease do not respond adequately to erythropoiesis-stimulating agent (ESA) treatment; these patients are referred to as ESA hyporesponders. There is no widely accepted contemporary definition for chronic ESA hyporesponse. The study objective was to propose and validate an operational definition for chronic ESA hyporesponse. METHODS: This was a retrospective cohort study using electronic health care records. Participants were anemic hemodialysis patients treated during February 2012 and were followed for 15 months. Patients' ESA response (responders) or lack of response (chronic and acute hyporesponders) based on longitudinal patterns of ESA dose and hemoglobin level was assessed. Persistence of hyporesponse, longitudinal iron measures, transfusion rates, and mortality rates were analyzed. Frequency of blood transfusions (monthly) and death rates (quarterly) were calculated. Log normalized serum ferritin concentration was analyzed. RESULTS: Of 97,677 eligible patients, 6632 had acute hyporesponsiveness (ESA responsiveness restituted in ≤ 4 months) and 3086 had chronic hyporesponsiveness (lack of ESA response for > 4 months). Over months 1-4 among chronic hyporesponders, mean serum ferritin (722-785 ng/mL) and transferrin saturation (TSAT; 26.76 %-27.08 %) were constant, while acute hyporesponsive patients experienced increased ferritin (654-760 ng/mL) and TSAT (25.71-30.88 %) levels. Compared to ESA responders (0.19-0.30 %), chronic hyporesponders were transfused 7-times (1.20-2.17 %) more frequently over follow-up. Quarterly mortality was greatest in chronic ESA hyporesponders (2.98-5.48 %), followed by acute ESA hyporesponders (2.17-3.30 %) and ESA responders (1.43-2.49 %). With consistence over the study, chronic hyporesponders died more frequently than patients in the other study cohorts. CONCLUSIONS: Findings indicate that 4 months of continuous ESA hyporesponsiveness can be used to differentiate acute from chronic hyporesponsiveness. This definition of chronic hyporesponsiveness is supported by outcome data showing higher mortality and transfusion rates in chronic hyporesponders compared to acute hyporesponders.

Effects of Crit-Line® monitor use on patient outcomes and epoetin alfa dosing following onset of hemodialysis: a propensity score-matched study.

BACKGROUND: The Crit-Line® monitor (CLM) is a device for monitoring hematocrit, oxygen saturation and change in intravascular blood volume during hemodialysis. Prior studies have evaluated CLM use in dialysis patients, but not specifically in those new to dialysis. METHODS: In this retrospective analysis, 199 patients initiating dialysis at 8 facilities routinely using CLM were compared with 796 propensity score-matched non-CLM patients initiating dialysis at facilities not using CLM. Outcomes were considered over the first 180 days on dialysis. RESULTS: Overall, the CLM group had higher StdKt/V (p = 0.06) and received lower doses of intravenous iron than the non-CLM group (p < 0.001). Erythropoiesis-stimulating agent doses were lower in the CLM group in months 1-5. Serum iron and transferrin saturation levels were higher overall for the CLM group than the non-CLM group (p = 0.004 and 0.01, respectively). Hemoglobin levels and time to first hospitalization were similar for both groups. CONCLUSION: Use of CLM is associated with lower erythropoiesis-stimulating agent and iron use in incident hemodialysis patients.

Use of the Tego needlefree connector is associated with reduced incidence of catheter-related bloodstream infections in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Catheter-related bloodstream infections (CRBSIs) are common in hemodialysis patients using central venous catheters, and catheter occlusion also occurs frequently. The Tego needlefree connector was developed to reduce the incidence of these complications; however, existing studies of its effectiveness and safety are limited. MATERIALS AND METHODS: This retrospective analysis compared outcomes among patients of a large dialysis organization receiving in-center hemodialysis using a central venous catheter with either the Tego connector or standard catheter caps between October 1 and June 30, 2013. Incidence rates for intravenous (IV) antibiotic starts, receipt of an IV antibiotic course, positive blood cultures, mortality, and missed dialysis treatments were calculated, and incidence-rate ratios (IRRs) were estimated using Poisson regression models. Utilization of erythropoiesis-stimulating agents (ESAs) and thrombolytics was described for each patient-month and compared using mixed linear models. Models were run without adjustment, adjusted for covariates that were imbalanced between cohorts, or fully adjusted for all potential confounders. RESULTS: The analysis comprised 10,652 Tego patients and 6,493 controls. Tego use was independently associated with decreased risk of CRBSI, defined by initiation of IV antibiotics (adjusted IRR 0.92, 95% confidence interval [CI] 0.87-0.97) or initiation of IV antibiotic course (adjusted IRR 0.89, 95% CI 0.84-0.95). Tego use was independently associated with decreased rate of missed dialysis treatments (adjusted IRR 0.98, 95% CI 0.97-1.00); no significant difference between Tego and control cohorts was observed with respect to mortality. Tego use was associated with decreased likelihood of thrombolytic use (adjusted per-month probability of 5.6% versus 6.2% for controls) and lower utilization of ESAs in study months 7-9. CONCLUSION: Use of the Tego connector may reduce the risk of CRBSI and result in lower utilization of thrombolytics, antibiotics, and ESAs, as well as fewer missed dialysis treatments.

RGS6 variants are associated with dietary fat intake in Hispanics: the IRAS Family Study.

Recently, a genome-wide association scan was completed in the IRAS (Insulin Resistance Atherosclerosis Study) Family Study (IRASFS) Hispanic-American cohort. Multiple single-nucleotide polymorphisms (SNPs) in the G-protein signaling 6 (RGS6) gene were found to be associated with adiposity phenotypes. RGS6 has shown downstream antagonistic interplay with opioid receptors, targets of fatty/sugary food agonists. The possibility that RGS6 promotes tolerance and tachyphylaxis among the opioid receptor is a plausible pathway for overconsuming fat/sugar-laden food. Therefore, we hypothesized that RGS6 variants are associated with intake of fatty/sugary foods. In 932 Hispanics from San Antonio and San Luis Valley, CO, the following dietary intake variables were assessed using the Block Brief 2000 food frequency questionnaire: total calories, total fat, % calories from fat, % calories from saturated fat, protein, % calories from protein, carbohydrates, % calories from carbohydrates, and daily frequency of servings of fats/oils/sweets. We tested for association between 23 SNPs in RGS6 and dietary intake using a variance components measured genotype approach. All models were adjusted for gender, recruitment site, admixture, BMI, and age. Using an additive genetic model, rs1402064 was associated with higher intake of fats/oils/sweets, total calories, total fat and saturated fat (P = 0.0007, 0.026, 0.023, and 0.024). SNPs rs847330 and rs847354 were associated with higher intake of fats/oils/sweets (P = 0.002 and 0.018), total fat (P = 0.040 and 0.048) and saturated fat (P = 0.044 and 0.041). Finally, rs769148 was associated with higher intake of fats/oils/sweets (P = 0.002). RGS6 is a new candidate gene for adiposity traits that may be associated with a behavioral tendency toward fat-laden food intake.

Variant in the 3' region of the IkappaBalpha gene associated with insulin resistance in Hispanic Americans: The IRAS Family Study.

The IKKbeta/NF-kappaB pathway is known to play an important role in inflammatory response and has also recently been implicated in the process of insulin resistance. We hypothesized that one or more variants in the IkappaBalpha gene (NFKBIA) or surrounding untranslated regions would be associated with insulin sensitivity (S(I)) in Hispanic-American families. We tested for association between 25 single-nucleotide polymorphisms (SNPs) in and near NFKBIA and S(I) in 981 individuals in 90 Hispanic-American families from the Insulin Resistance Atherosclerosis (IRAS) Family Study. SNP rs1951276 in the 3' flanking region of NFKBIA was associated with S(I) in the San Antonio (SA) sample after adjusting for age, gender, and admixture (uncorrected P = 1.69 x 10(-5); conservative Bonferroni correction P = 3.38 x 10(-4)). Subjects with at least one A allele for NFKBIA rs1951276 had approximately 29% lower S(I) compared to individuals homozygous for the G allele in the SA sample. Although not statistically significant, the effect was in the same direction in the San Luis Valley (SLV) sample alone (P = 0.348) and was significant in the combined SA and SLV samples (P = 5.37 x 10(-4); presence of A allele associated with approximately 20% lower S(I)). In SA, when adjusted for subcutaneous adipose tissue area (SAT, cm(2)), the association was modestly attenuated (P = 1.25 x 10(-3)), but the association remained highly significant after adjustment for visceral adipose tissue area (VAT, cm(2); P = 4.41 x 10(-6)). These results provide corroborating evidence that the NF-kappaB/IKKbeta pathway may mediate obesity-induced insulin resistance in humans.