Higher Doses of Erythropoietin-Stimulating Agents and Hyporesponsiveness to Their Effects Are Associated with Increased Mortality among Prevalent Hemodialysis Patients

Abstract

Background: Attempts to achieve near-normal hemoglobin levels have been associated with higher mortality among chronic kidney disease patients. Evidence suggests a higher mortality rate for those with resistance to erythropoietin-stimulating agents (ESA). We investigated the association between responsiveness to ESA, dose of ESA and mortality in our hemodialysis population. Methods: A retrospective cohort study of chronic hemodialysis patients receiving dialysis was conducted at the University of Virginia facilities. We collected data on patient demographics, comorbidities, dialysis vintage, vascular access type, body weight, ESA dose and hemoglobin, as well as data on known risk factors for ESA hyporesponsiveness. Vital status was determined 30 months later. The association between ESA responsiveness and mortality was investigated by using the Cox proportional hazard model adjusting for demographics, comorbidities, access type, dialysis adequacy, serum albumin, serum parathyroid hormone and ferritin concentrations. Results: A total of 606 patients were included. The overall 30-month mortality was 35.8%. Compared to those in the lowest tertile of ESA hyporesponsiveness, patients in the middle and upper tertiles had significantly higher mortality (hazard ratio, HR: 1.64, 95% CI: 1.14-2.37, and HR: 2.08, 95% CI: 1.46-2.97, respectively). In the Cox proportional hazard model each unit increment in the ESA resistance index was associated with an HR of 2.27 (95% CI: 1.60-3.23) for mortality. In this model each 1-unit increment in ESA dose/kg or each 100-μg increment in absolute darbepoetin alfa dose were associated with a 9% increased risk of mortality (HR: 1.09, 95% CI: 1.04-1.13, and HR: 1.09, 95% CI: 1.03-1.15, respectively). Conclusions: Among prevalent hemodialysis patients, a higher degree of resistance to and higher doses of ESA are associated with increased mortality.

Minor Elevation in C-Reactive Protein Levels Predicts Incidence of Erythropoiesis-Stimulating Agent Hyporesponsiveness among Hemodialysis Patients

“…However, about 5-10% of patients exhibit suboptimal responses to ESAs, despite receiving a high dose [1] and are dubbed to be hyporesponsive to ESAs. Given that ESA hyporesponsiveness subsequently leads to exacerbation of morbidity and mortality [2,3], this issue must be dealt with promptly. Several risk factors for ESA hyporesponsiveness have been identified [4], including inadequate iron administration [5], malnutrition [6,7], malignancy, vitamin deficiency [8] and administration of certain drug types, such as renin-angiotensin system inhibitors [9].…”

Erythropoietin Resistance Index and the All-Cause Mortality of Chronic Hemodialysis Patients

“…Fukuma et al [24] recently reported finding an association between ESA hyporesponsiveness and mortality in a large cohort of Japanese HD patients. More recently, Nishio et al [25] have shown associations of both higher degree of ESA resistance and higher doses of ESA with increased mortality among prevalent HD patients.…”

The Complete Study of the Switch from Iron-Sucrose Originator to Iron- Sucrose Similar and Vice Versa in Hemodialysis Patients

“…The followup period was adequate for analyzing the effects of the treatment on anemia parameters, but it was not valid for evaluating the long-term outcomes associated with each formulation. Further to above specified potential iron accumulation in tissues such as liver, heart and kidney, high doses of ESAs [43,44] and/or IV iron [45,46] have been linked to increased mortality in HD patients. In this study the use of iron sucrose similar is associated with higher ESA doses and higher IV iron doses, than with the IV iron original formulation.…”