Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Temporal Trends in Hemoglobin, Use of Erythropoiesis Stimulating Agents, and Major Clinical Outcomes in Incident Dialysis Patients in Canada.

ABSTRACT:

Introduction

Several jurisdictions have adopted a more conservative approach to anemia in patients receiving dialysis amid safety concerns from target hemoglobin studies. It is largely unknown if this has contributed to a change in clinical outcomes.

Methods

A national registry was used to identify 35,945 adult patients who initiated and were maintained on dialysis for ≥90 days in Canada from January 2007 to December 2015. Outcomes were ascertained until March 2017 via linkage with hospital discharge diagnoses. Cox proportional hazards models were used to investigate the association between the era of dialysis initiation and the primary composite outcome (acute myocardial infarction [AMI], stroke, or mortality).

Results

The mean hemoglobin at dialysis initiation decreased from 102.9 g/l in 2007 to 95.5 g/l in 2015, corresponding with a higher prevalence of hemoglobin <80 g/l (8% to 17%) and a reduction in erythropoiesis stimulating agent (ESA) use (49% to 44%). After multivariable adjustment, Era 3 (2013-2015) was associated with an 8% relative risk reduction in the primary outcome compared with Era 1 (2007-2009) (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.88-0.96), a 10% relative reduction in mortality (HR 0.90, 95% CI 0.85-0.94) but no significant change in AMI or stroke. In a model without era, neither hemoglobin nor ESA use was an independent predictor of outcome.

Conclusion

There have been modest declines in average hemoglobin values and ESA use among incident dialysis patients in Canada with no change in major cardiovascular outcomes. Patient survival has improved over time, likely for reasons other than anemia management.

SUBMITTER: Canney M

PROVIDER: S-EPMC8071619 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Effect of erythropoiesis-stimulating agents on blood pressure in pre-dialysis patients.

Project description:INTRODUCTION: Erythropoiesis-Stimulating Agents (ESA) are hypothesized to increase cardiovascular mortality in patients with chronic kidney disease. One of the proposed mechanisms is the elevation of blood pressure (BP) by ESA. Therefore, we aimed to determine whether the use of ESA was associated with antihypertensive treatment and higher BP. MATERIALS AND METHODS: In this cohort 502 incident pre-dialysis patients were included who started specialized pre-dialysis care in 25 clinics in the Netherlands. Data on medication including ESA use and dose, co-morbidities and BP were routinely collected every 6 months. Antihypertensive treatment and BP were compared for patients with and without ESA at baseline. Differences in antihypertensive medication and BP during pre-dialysis care were estimated with linear mixed models adjusted for age, sex, body mass index, cardiovascular disease, diabetes mellitus and estimated glomerular filtration rate. RESULTS: At baseline, 95.6% of patients with ESA were treated with antihypertensive medication and 73.1% of patients without ESA. No relevant difference in BP was found. During pre-dialysis care patients with ESA used 0.77 (95% CI 0.63;0.91) more classes of antihypertensive drugs. The adjusted difference in systolic blood pressure (SBP) was -0.3 (95% CI -2.7;2.0) mmHg and in diastolic blood pressure (DBP) was -1.0 (95% CI -2.1;0.3) mmHg for patients with ESA compared to patients without ESA. Adjusted SBP was 3.7 (95% CI -1.6;9.0) mmHg higher in patients with a high ESA dose compared to patients with a low ESA dose. CONCLUSIONS: Our study confirms the hypertensive effect of ESA, since ESA treated patients received more antihypertensive agents. However, no relevant difference in BP was found between patients with and without ESA, thus the increase in BP seems to be controlled for by antihypertensive medication.

| S-EPMC3877353 | biostudies-literature

Effect of Medicare dialysis payment reform on use of erythropoiesis stimulating agents.

Project description:ObjectiveIn 2011, the Centers for Medicare and Medicaid Services (CMS) replaced fee-for-service reimbursement for erythropoiesis stimulating agents (ESAs) with a fixed-sum bundled payment for all dialysis-related care and pay-for-performance incentives to discourage maintaining patients' hematocrits above 36 percent. We examined the impact of the new payment policy on the use of ESAs.Data sourcesCMS's Renal Information Management System.Study designRegression discontinuity design assessing the use of ESAs by hematocrit level before and after the implementation of the payment policy change.Data extractionSecondary data from 424,163 patients receiving hemodialysis treatment between January 2009 and June 2011.Principal findingsThe introduction of bundled payments with pay-for-performance initiatives was associated with an immediate and substantial decline in the use of ESAs among patients with hematocrit >36 percent and little change in the use of ESAs among patients with hematocrit ≤36 percent. In the first two quarters of 2011, the use of ESAs during dialysis fell by about 7-9 percentage points among patients with hematocrit levels >36 percent. No statistically significant differences in ESA use were observed at the thresholds of 30 or 33 percent.ConclusionsCMS's payment reform for dialysis care reduced the use of ESAs in patients who may not benefit from these agents.

| S-EPMC4450930 | biostudies-literature

Association of dialysis facility-level hemoglobin measurement and erythropoiesis-stimulating agent dose adjustment frequencies with dialysis facility-level hemoglobin variation: a retrospective analysis.

Project description:BackgroundA key goal of anemia management in dialysis patients is to maintain patients' hemoglobin (Hb) levels consistently within a target range. Our aim in this study was to assess the association of facility-level practice patterns representing Hb measurement and erythropoiesis-stimulating agent (ESA) dose adjustment frequencies with facility-level Hb variation.MethodsThis was a retrospective observational database analysis of patients in dialysis facilities affiliated with large dialysis organizations as of July 01, 2006, covering a follow-up period from July 01, 2006 to June 30, 2009. A total of 2,763 facilities representing 436,442 unique patients were included. The predictors evaluated were facility-level Hb measurement and ESA dose adjustment frequencies, and the outcome measured was facility-level Hb variation.ResultsFirst to 99th percentile ranges for facility-level Hb measurement and ESA dose adjustment frequencies were approximately once per month to once per week and approximately once per 3 months to once per 3 weeks, respectively. Facility-level Hb measurement and ESA dose adjustment frequencies were inversely associated with Hb variation. Modeling results suggested that a more frequent Hb measurement (once per week rather than once per month) was associated with approximately 7% to 9% and 6% to 8% gains in the proportion of patients with Hb levels within a ±1 and ±2 g/dL range around the mean, respectively. Similarly, more frequent ESA dose adjustment (once per 2 weeks rather than once per 3 months) was associated with approximately 6% to 9% and 5% to 7% gains in the proportion of patients in these respective Hb ranges.ConclusionsFrequent Hb measurements and timely ESA dose adjustments in dialysis patients are associated with lower facility-level Hb variation and an increase in proportion of patients within ±1 and ±2 g/dL ranges around the facility-level Hb mean.

| S-EPMC3123272 | biostudies-literature

Mortality associated with dose response of erythropoiesis-stimulating agents in hemodialysis versus peritoneal dialysis patients.

Project description:BackgroundSeveral studies have shown an association between erythropoietin-stimulating agent (ESA) responsiveness and mortality in chronic kidney disease (CKD) patients. In our present study, we examined the association between prescribed ESA dose and mortality in peritoneal dialysis (PD) and hemodialysis (HD) patients. We hypothesized that PD patients received lower ESA dose for the same achieved hemoglobin compared to HD patients and that ESA dose-mortality associations were different between PD and HD patients.MethodsWe compared the prescribed doses of ESA between 139,103 HD and 10,527 PD patients treated in DaVita dialysis clinics from 7/2001 through 6/2006 using adjusted Poisson regression and examined mortality-predictability of prescribed ESA dose and ESA responsiveness index (ESA/hemoglobin) in PD and HD with follow-up through 6/2007 using Cox regression models.ResultsPoisson adjusted ratio of ESA dose of HD to PD was 3.6 (95% CI 3.5-3.7). In PD patients, adjusted all-cause death hazard ratios (HR) for ESA doses of 3,000-5,999, 6,000-8,999 and ?9,000 U/week (reference <3,000 U/week) were 0.97 (0.87-1.07), 0.85 (0.76-0.95) and 1.08 (0.98-1.18), respectively; whereas in HD patients across commensurate ESA dose increments of 10,000-19,999, 20,000-29,999 and ?30,000 U/week (reference <10,000 U/week) were 1.14 (1.11-1.17), 1.54 (1.50-1.58) and 2.15 (2.10-2.21), respectively. In PD and HD patients, the adjusted death HR of the 4th to 1st quartile of ESA responsiveness index were 1.14 (1.04-1.26) and 2.37 (2.31-2.43), respectively.ConclusionsBetween 2001 and 2006, most PD patients received substantially lower ESA dose for same achieved hemoglobin levels, and low ESA responsiveness was associated with higher mortality in both HD and PD patients.

| S-EPMC3326284 | biostudies-literature

Pharmacovigilance in practice: erythropoiesis-stimulating agents.

Project description:Pharmacovigilance (PV) is the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or other problems related to medical products after they have been licensed for marketing. The purpose of PV is to advance the safe use of marketed medical products. Regulatory agencies and license holders collaborate to collect data reported by health care providers, patients, and the public as well as data from systematic reviews, meta-analyses, and individual clinical and nonclinical studies. They validate and analyze the data to determine whether safety signals exist, and if warranted, develop an action plan to mitigate the identified risk. Erythropoiesis-stimulating agents (ESAs) provide an example of how PV is applied in reality. Among other approved indications, ESAs may be used to treat anemia in patients with chemotherapy-induced anemia. ESAs increase hemoglobin levels and reduce the need for transfusions; they are also associated with a known increased risk of thromboembolic events. Starting in 2003, emerging data suggested that ESAs might reduce survival. As a result of PV activities by regulatory agencies and license holders, labeling for ESAs addresses these risks. Meta-analyses and individual clinical studies have confirmed that ESAs increase the risk of thromboembolic events, but when used as indicated, ESAs have not been shown to have a significant effect on survival or disease progression. Ongoing safety studies will provide additional data in the coming years to further clarify the risks and benefits of ESAs.

| S-EPMC4302692 | biostudies-other

Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents.

Project description:BackgroundVadadustat, an inhibitor of hypoxia-inducible factor prolyl-4-hydroxylase domain dioxygenases, is an oral investigational agent in development for the treatment of anemia secondary to chronic kidney disease.MethodsIn this open-label Phase 2 trial, vadadustat was evaluated in 94 subjects receiving hemodialysis, previously maintained on epoetin alfa. Subjects were sequentially assigned to one of three vadadustat dose cohorts by starting dose: 300 mg once daily (QD), 450 mg QD or 450 mg thrice weekly (TIW). The primary endpoint was mean hemoglobin (Hb) change from pre-baseline average to midtrial (Weeks 7-8) and end-of-trial (Weeks 15-16) and was analyzed using available data (no imputation).ResultsOverall, 80, 73 and 68% of subjects in the 300 mg QD, 450 mg QD, and 450 mg TIW dose cohorts respectively, completed the study. For all dose cohorts no statistically significant mean change in Hb from pre-baseline average was observed, and mean Hb concentrations-analyzed using available data-remained stable at mid- and end-of-trial. There was one subject with an Hb excursion >13 g/dL. Overall, 83% of subjects experienced an adverse event (AE); the proportion of subjects who experienced at least one AE was similar among the three dose cohorts. The most frequently reported AEs were nausea (11.7%), diarrhea (10.6%) and vomiting (9.6%). No deaths occurred during the study. No serious AEs were attributed to vadadustat.ConclusionsVadadustat maintained mean Hb concentrations in subjects on hemodialysis previously receiving epoetin. These data support further investigation of vadadustat to assess its long-term safety and efficacy in subjects on hemodialysis.

| S-EPMC6322440 | biostudies-literature

Serum trace metal association with response to erythropoiesis stimulating agents in incident and prevalent hemodialysis patients.

Project description:Alterations in hemodialysis patients' serum trace metals have been documented. Early studies addressing associations levels of serum trace metals with erythropoietic responses and/or hematocrit generated mixed results. These studies were conducted prior to current approaches for erythropoiesis stimulating agent (ESA) drug dosing guidelines or without consideration of inflammation markers (e.g. hepcidin) important for regulation of iron availability. This study sought to determine if the serum trace metal concentrations of incident or chronic hemodialysis patients associated with the observed ESA response variability and with consideration to ESA dose response, hepcidin, and high sensitivity C-reactive protein levels. Inductively-coupled plasma-mass spectrometry was used to measure 14 serum trace metals in 29 incident and 79 prevalent dialysis patients recruited prospectively. We compared these data to three measures of ESA dose response, sex, and dialysis incidence versus dialysis prevalence. Hemoglobin was negatively associated with ESA dose and cadmium while positively associated with antimony, arsenic and lead. ESA dose was negatively associated with achieved hemoglobin and vanadium while positively associated with arsenic. ESA response was positively associated with arsenic. Vanadium, nickel, cadmium, and tin were increased in prevalent patients. Manganese was increased in incident patients. Vanadium, nickel, and arsenic increased with time on dialysis while manganese decreased. Changes in vanadium and manganese were largest and appeared to have some effect on anemia. Incident and prevalent patients' chromium and antimony levels exceeded established accepted upper limits of normal.

| S-EPMC7677396 | biostudies-literature

Treatment of renal anemia: Erythropoiesis stimulating agents and beyond.

Project description:Anemia, complicating the course of chronic kidney disease, is a significant parameter, whether interpreted as subjective impairment or an objective prognostic marker. Renal anemia is predominantly due to relative erythropoietin (EPO) deficiency. EPO inhibits apoptosis of erythrocyte precursors. Studies using EPO substitution have shown that increasing hemoglobin (Hb) levels up to 10-11 g/dL is associated with clinical improvement. However, it has not been unequivocally proven that further intensification of erythropoiesis stimulating agent (ESA) therapy actually leads to a comprehensive benefit for the patient, especially as ESAs are potentially associated with increased cerebro-cardiovascular events. Recently, new developments offer interesting options not only via stimulating erythropoeisis but also by employing additional mechanisms. The inhibition of activin, a member of the transforming growth factor superfamily, has the potential to correct anemia by stimulating liberation of mature erythrocyte forms and also to mitigate disturbed mineral and bone metabolism as well. Hypoxia-inducible factor prolyl hydroxylase inhibitors also show pleiotropic effects, which are at the focus of present research and have the potential of reducing mortality. However, conventional ESAs offer an extensive body of safety evidence, against which the newer substances should be measured. Carbamylated EPO is devoid of Hb augmenting effects whilst exerting promising tissue protective properties. Additionally, the role of hepcidin antagonists is discussed. An innovative new hemodialysis blood tube system, reducing blood contact with air, conveys a totally different and innocuous option to improve renal anemia by reducing mechanical hemolysis.

| S-EPMC5592888 | biostudies-other

Quantitative assessment of minimal effective concentration of erythropoiesis-stimulating agents.

Project description:Minimal effective concentration (MEC) was proposed to explain why subcutaneous (SC) administration of erythropoietin (EPO) induces a higher hemoglobin (HGB) increase than intravenous (IV) administration. It has been further used to explain the paradox that erythropoiesis-stimulating agent (ESA) with lower receptor binding affinity may have higher in vivo activity. We have developed a pharmacokinetic and pharmacodynamic (PK/PD) model with incorporation of the operational model of agonism to characterize the data from two clinical trials. By using model-based simulations, we demonstrate that SC route is more efficacious than IV route and explain the paradoxical behavior of ESAs. We determined that MEC can be quantified by C50, which represents the concentration of an ESA producing its half-maximal effect of stimulating the proliferation of erythroid precursor cells. The model used may allow joint PK/PD modeling of data from different ESAs, and provide a platform for dosing regimen optimizations and future clinical study designs.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e62; doi:10.1038/psp.2013.39; published online 7 August 2013.

| S-EPMC3828003 | biostudies-literature

Erythropoiesis-stimulating agents and other methods to enhance oxygen transport.

Project description:Oxygen is essential for life, and the body has developed an exquisite method to collect oxygen in the lungs and transport it to the tissues. Hb contained within red blood cells (RBCs), is the key oxygen-carrying component in blood, and levels of RBCs are tightly controlled according to demand for oxygen. The availability of oxygen plays a critical role in athletic performance, and agents that enhance oxygen delivery to tissues increase aerobic power. Early methods to increase oxygen delivery included training at altitude, and later, transfusion of packed RBCs. A breakthrough in understanding how RBC formation is controlled included the discovery of erythropoietin (Epo) and cloning of the EPO gene. Cloning of the EPO gene was followed by commercial development of recombinant human Epo (rHuEpo). Legitimate use of this and other agents that affect oxygen delivery is important in the treatment of anaemia (low Hb levels) in patients with chronic kidney disease or in cancer patients with chemotherapy-induced anaemia. However, competitive sports was affected by illicit use of rHuEpo to enhance performance. Testing methods for these agents resulted in a cat-and-mouse game, with testing labs attempting to detect the use of a drug or blood product to improve athletic performance (doping) and certain athletes developing methods to use the agents without being detected. This article examines the current methods to enhance aerobic performance and the methods to detect illicit use.

| S-EPMC2439521 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data