Comparative Effectiveness of mRNA-based BNT162b2 Vaccine versus Adenovirus Vector-Based Ad26.COV2.S Vaccine for the Prevention of COVID-19 among Dialysis Patients.

BACKGROUND: Studies have demonstrated that mRNA-based SARS-CoV-2 vaccines are highly effective among patients on dialysis. Because individual vaccines may be differentially available or acceptable to patients, it is important to understand comparative effectiveness relative to other vaccines, such those on the basis of adenovirus technologies. METHODS: In this retrospective study, we compared the clinical effectiveness of adenovirus vector-based Ad26.COV2.S (Janssen/Johnson & Johnson) to mRNA-based BNT162b2 (Pfizer/BioNTech) in a contemporary cohort of patients on dialysis. Patients who received a first BNT162b2 dose were matched 1:1 to Ad26.COV2.S recipients on the basis of date of first vaccine receipt, US state of residence, site of dialysis care (in-center versus home), history of COVID-19, and propensity score. The primary outcome was the comparative rate of COVID-19 diagnoses starting in the 7th week postvaccination. In a subset of consented patients who received Ad26.COV2.S, blood samples were collected ≥28 days after vaccination and anti-SARS-CoV-2 immunoglobulin G antibodies were measured. RESULTS: A total of 2572 matched pairs of patients qualified for analysis. Cumulative incidence rates of COVID-19 did not differ for BNT162b2 versus Ad26.COV2.S. No differences were observed in peri-COVID-19 hospitalizations and deaths among patients receiving BNT162b2 versus Ad26.COV2.S, who were diagnosed with COVID-19 during the at-risk period. Results were similar when excluding patients with a history of COVID-19, in subgroup analyses restricted to patients who completed the two-dose BNT162b2 regimen, and in patients receiving in-center hemodialysis. SARS-CoV-2 antibodies were detected in 59.4% of 244 patients who received Ad26.COV2.S. CONCLUSIONS: In a large real-world cohort of patients on dialysis, no difference was detected in clinical effectiveness of BNT162b2 and Ad26.COV2.S over the first 6 months postvaccination, despite an inconsistent antibody response to the latter.

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.

The effect of altitude on erythropoiesis-stimulating agent dose, hemoglobin level, and mortality in hemodialysis patients.

Residence at higher altitude has been associated with improved anemia parameters and lower mortality rates among end-stage renal disease (ESRD) patients. However, these associations were observed prior to the 2011 shift in erythropoiesis-stimulating agent (ESA) dosing. To determine the impact of altitude on contemporary ESRD patients, a retrospective observational analysis was conducted in which patients were ascribed to one of four altitude categories as of 1 Jan 2012 and outcomes were assessed during 2012. Associations between altitude category and outcomes were estimated using generalized linear mixed models, adjusted for covariates that differed at baseline. Patients at higher altitude were less likely to receive ESA treatment, and dose was 723 U/treatment (95 % confidence interval [CI]: 544, 834) lower in the highest altitude category compared to the lowest category. The proportion of patients using IV iron decreased with increasing altitude category. Patients in the highest two categories had greater mean hemoglobin values (+0.15 and +0.23 g/dL) than the lowest. Mortality was lower for patients in the highest altitude category compared to those in the lowest (incidence rate ratio 0.73; 95 % CI: 0.63, 0.88), although their rate of missed dialysis treatments was slightly higher. This study confirms that, in the context of current anemia management practices, high altitude is associated with higher hemoglobin and lower mortality, despite lower utilization of ESA and IV iron.

Comparative Effectiveness of Dialyzers: A Longitudinal, Propensity Score-Matched Study of Incident Hemodialysis Patients.

Differences in dialyzer design may have consequences for patient outcomes. We evaluated the comparative effectiveness of commonly used dialyzers with respect to measures of dialysis treatment, anemia management, inflammation, and dialyzer clotting. Patients receiving hemodialysis between January 1, 2009, and December 31, 2013, and using polyarylethersulfone-polyvinylpyrrolidone (PAS-PVP; Polyflux Revaclear) or polysulfone (PS; Optiflux 160 or Optiflux 180) dialyzers were followed for 1 year or until end of study or censoring for dialyzer switch, modality change, or loss to follow-up. For each comparison, eligible patients were propensity score-matched 1:1 on a range of baseline characteristics. Outcomes were assessed using generalized linear mixed models. Dialysis adequacy was similar in both dialyzer groups. Erythropoiesis-stimulating agent (ESA) doses were lower for patients using PAS-PVP versus patients using PS-160 (difference range: 75-589 units/treatment; statistically significant in months 1-5 and 7) and for patients using PAS-PVP versus patients using PS-180 (difference range: 27-591 unit/treatment; statistically significant in months 1-9). Intravenous iron doses trended lower for patients using PAS-PVP versus patients using PS, but hemoglobin concentrations were equivalent. In conclusion, use of PAS-PVP versus PS dialyzers was associated with equivalent dialysis adequacy, lower ESA doses, modestly lower Intravenous iron doses, and equivalent hemoglobin concentrations.

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.

Clinical characteristics and outcomes of end-stage renal disease patients with self-reported pruritus symptoms.

One of the most common conditions affecting end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) is pruritus. Studies report that itchy and dry skin, symptoms of pruritus, affect 40%-90% of ESRD patients. Yet, in clinical practice the condition is often underdiagnosed resulting in inadequate management and an underappreciated impact on patient outcomes. Two retrospective analyses were conducted: a preliminary analysis of ESRD patients with pruritus symptoms (n=73,124) undergoing HD or peritoneal dialysis at a large dialysis provider and a subsequent detailed analysis of a homogenous subset of patients undergoing in-center HD (n=38,315). The goal was to better understand the clinical burden of pruritus as it relates to patient characteristics, quality of life, medication use, and HD compliance. This population is commonly burdened by multiple comorbidities and related polypharmaceutical management; identifying the relationship of pruritus to these ailments can help guide future research and resource allocation. The detailed analysis confirmed trends observed in the preliminary analysis: 30% reported being "moderately" to "extremely bothered" by itchiness. The HD patient population with the highest severity of self-reported pruritus also had a consistent trend in overall increased resource utilization - higher monthly doses of erythropoietin-stimulating agents (53,397.1 to 63,405.4 units) and intravenous (IV) iron (237.2 to 247.6 units) and higher use of IV antibiotics (14.1% to 20.7%), as well as poorer quality-of-life measures (25-point reductions in Burden of Disease Score and Effects on Daily Life subscales of the Kidney Disease Quality of Life-36 survey). These results highlight the need to better identify and manage ESRD patients impacted by pruritus, as this symptom is associated with negative clinical outcomes and increased resource utilization. Further studies are needed to evaluate the current economic burden of pruritus in ESRD patients and create possible options for an improved pharmacoeconomic profile in this patient population.