Epoetin requirements predict mortality in hemodialysis patients

Zhang, Yi; Thamer, Mae; Stefanik, Kevin; Kaufman, James S.; Cotter, Dennis J.

doi:10.1016/s0272-6386(04)01086-8

Cited by 168 publications

(109 citation statements)

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“…ESA-sensitive patients derive survival benefits from the full correction of anemia, whereas patients with ESA resistance (which is a predictor of poor survival) may be harmed by the high doses of ESA prescribed in the attempt to increase Hb levels [44, 45]; however, this is still under debate [46]. Although higher Hb targets have been suggested to reduce the need for transfusions and have beneficial effects on the quality of life of patients [9–11], disadvantages have also been reported [12–14].…”

Section: Discussionmentioning

confidence: 99%

Relationship between Hemoglobin Levels Corrected by Interdialytic Weight Gain and Mortality in Japanese Hemodialysis Patients: Miyazaki Dialysis Cohort Study

et al. 2017

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BackgroundAlthough hemoglobin (Hb) levels are affected by a change in the body fluid status, the relationship between Hb levels and mortality while taking interdialytic weight gain (IDWG) at blood sampling into account has not yet been examined in hemodialysis patients.Study designCohort study.Setting, ParticipantsData from the Miyazaki Dialysis cohort study, including 1375 prevalent hemodialysis patients (median age (interquartile range), 69 (60–77) years, 42.3% female).PredictorPatients were divided into 5 categories according to baseline Hb levels and two groups based on the median value of IDWG rates at blood sampling at pre-HD on the first dialysis session of the week.OutcomesAll-cause and cardiovascular mortalities during a 3-year follow-up.MeasurementsHazard ratios were estimated using a Cox model for the relationship between Hb categories and mortality, and adjusted for potential confounders such as age, sex, dialysis duration, erythropoiesis-stimulating agent dosage, Kt/V, comorbid conditions, anti-hypertensive drug use, serum albumin, serum C-reactive protein, serum ferritin, and serum intact parathyroid hormone. Patients with Hb levels of 9–9.9 g/dL were set as our reference category.ResultsA total of 246 patients (18%) died of all-cause mortality, including 112 cardiovascular deaths. Lower Hb levels (<9.0g/dL) were associated with all-cause mortality (adjusted HRs 2.043 [95% CI, 1.347–3.009]), while Hb levels were not associated with cardiovascular mortality. When patients were divided into two groups using the median value of IDWG rates (high IDWG, ≥5.4% and low IDWG, <5.4%), the correlation between lower Hb levels and all-cause mortality disappeared in high IDWG patients, but was maintained in low IDWG patients (adjusted HRs 3.058 [95% CI,1.575–5.934]). On the other hand, higher Hb levels (≥12g/dL) were associated with cardiovascular mortality in high IDWG patients (adjusted HRs 2.724 [95% CI, 1.010–7.349]), but not in low IDWG patients.ConclusionIn hemodialysis patients, target Hb levels may need to be selected in consideration of IDWG at blood sampling.

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Section: Discussionmentioning

confidence: 99%

Relationship between Hemoglobin Levels Corrected by Interdialytic Weight Gain and Mortality in Japanese Hemodialysis Patients: Miyazaki Dialysis Cohort Study

et al. 2017

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“…Randomized trials have shown increased mortality 1 or no beneficial clinical effects 2 among those assigned to normal Hct targets, and observational studies 3,4 have found no survival benefits among hemodialysis patients receiving high ESA doses.…”

Section: Introductionmentioning

confidence: 99%

High doses of epoetin do not lower mortality and cardiovascular risk among elderly hemodialysis patients with diabetes

Zhang

Thamer

Kaufman

et al. 2011

Kidney International

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Summary Background Whether exposure to high erythropoiesis-stimulating agents (ESA) doses results in adverse cardiovascular outcomes in hemodialysis patients based on the presence of diabetes has been suggested by an earlier randomized trial but remains inconclusive. Methods Data from the US Renal Data System were used to identify 35,593 Medicare patients on hemodialysis: 19,034 (53%) were diabetic. We fit a pooled logistic model to estimate the probability of mortality and a composite cardiovascular end point at each month using inverse probability (IP) weighting to adjust for time-dependent confounding by indication. IP weights were estimated separately for diabetic and nondiabetic cohorts. Findings The adjusted 9-month mortality risk difference between an ESA dose of 45,000 U/wk and 15,000 U/wk was 13% among diabetics and 5% among nondiabetics (p value = 0.002). Compared with a dose of 20,000 – 30,000 U/wk, the hazard ratio of mortality was 1.32 (95% CI 1.11, 1.58) and the hazard ratio of a composite endpoint of death and cardiovascular events was 1.26 (95% CI 1.07, 1.50) among diabetic patients exposed to the highest ESA doses (>40,000 U/wk). The corresponding hazard ratios in non-diabetic patients were 1.06 (95% CI 0.88, 1.28) and 1.10 (95% CI 0.92, 1.32), respectively. Interpretation Using higher ESA doses as usually necessary to achieve higher hemoglobins appears to be not beneficial, and possibly harmful, to diabetic patients. Little effect of dose was found in nondiabetic patients. Our study findings support the FDA’s recent advisories recommending that the lowest possible ESA dose be used when treating hemodialysis patients.

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“…Additionally, primary outcomes for both trials were composites (including death, myocardial infarction or stroke in CHOIR, death or cardiovascular event including stroke in TREAT) [7, 10]. Other observational studies in adults have shown that ESA dose requirement is a predictor of mortality in adults on HD, independent of hematocrit level [19]. An advantage of examining the association between ESA dose and mortality in a pediatric dialysis cohort is that the prevalence of advanced cardiovascular disease in these patients is comparatively low, and thus we are able to characterize the association without the significantly increased risk conferred to older adults.…”

Section: Discussionmentioning

confidence: 99%

Association of higher erythropoiesis stimulating agent dose and mortality in children on dialysis

2014

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Background Higher doses of erythropoiesis-stimulating agents (ESA) have been associated with an increased risk of adverse outcomes in adults with chronic kidney disease (CKD) and end-stage kidney disease (ESRD), but to our knowledge no trials have been performed in children. We examined the association between ESA dose and all-cause mortality in a prevalent pediatric dialysis population. Methods Retrospective cohort study utilizing national data on all prevalent dialysis patients aged <18 years from the Centers for Medicare and Medicaid Services’ 2005 ESRD Clinical Performance Measures (CPM) project, linked to 18-month mortality records from the United States Renal Data System. Multivariate Cox proportional hazards regression was performed to determine the risk of mortality by mean weekly ESA dose. Results Eight-hundred and twenty-nine children were included in the analysis; 7 % died during follow-up. A higher proportion of patients receiving ESA doses in the highest category (erythropoietin ≥350 units/kg/week or darbepoetin ≥1.5 units/kg/week) died (50 % vs 28 %, p=0.002), and also demonstrated a trend toward lower hemoglobin (11.0 vs 11.4 g/dL, p=0.05). In multivariate analysis, patients receiving the highest dose of ESA demonstrated an increased risk of mortality (hazard ratio 3.37; p value <0.01). Conclusion Higher ESA dose is independently associated with mortality in children on chronic dialysis.

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Epoetin requirements predict mortality in hemodialysis patients

Cited by 168 publications

References 0 publications

Relationship between Hemoglobin Levels Corrected by Interdialytic Weight Gain and Mortality in Japanese Hemodialysis Patients: Miyazaki Dialysis Cohort Study

Relationship between Hemoglobin Levels Corrected by Interdialytic Weight Gain and Mortality in Japanese Hemodialysis Patients: Miyazaki Dialysis Cohort Study

High doses of epoetin do not lower mortality and cardiovascular risk among elderly hemodialysis patients with diabetes

Association of higher erythropoiesis stimulating agent dose and mortality in children on dialysis

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