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

Abstract

Background: Evidence suggests hemodialysis (HD) patients with resistance to erythropoiesis-stimulating agents (ESA) have a higher mortality rate. We investigated the association between ESA responsiveness and mortality in our HD population. Methods: A prospective cohort study of chronic HD patients was conducted at Jyoban Hospital in Fukushima, Japan. We collected data on patient demographic factors, comorbidities, dialysis vintage, body weight, ESA dose and hemoglobin concentration, as well as data on known risk factors for ESA hyporesponsiveness. The erythropoietin resistance index (ERI) was calculated by dividing the weekly body-weight-adjusted epoetin dose by the hemoglobin concentration. The association between ESA hyporesponsiveness estimated by the highest tertile of ERI and mortality was investigated by using the Cox proportional hazards model with adjustments for demographic factors, comorbidities, dialysis adequacy and serum biochemical data. Results: A total of 248 patients were included as subjects in the cohort, and their overall 2-year mortality rate was 13.3%. According to the results of the Kaplan-Meier analysis, patients with an ERI in the highest tertile had significantly higher mortality than patients with an ERI in the lower two tertiles (p = 0.0121). The highest ERI tertile was associated with higher all-cause mortality in both the unadjusted hazards model (hazard ratio, HR: 4.429; 95% CI: 1.249-15.704) and the adjusted hazards model (HR: 4.204; 95% CI: 1.173-15.065). Conclusions: A higher degree of resistance to ESA in chronic HD patients is associated with increased mortality.

The Virtual Anemia Trial: An Assessment of Model‐Based In Silico Clinical Trials of Anemia Treatment Algorithms in Patients With Hemodialysis

“…Second, we must better understand our patients’ (patho)physiology, something our modeling approach can deliver. For example, resistance to ESA is a major clinical concern and has been associated with increased patient morbidity and mortality 31. However, ESA resistance is defined solely based on the presence of an ESA requirement above some threshold (several definitions exist in the literature).…”

The HIF System Response to ESA Therapy in CKD‐Anemia

“…According to the KDIGO guidelines [49], CKD patients can present initial or acquired ESA hyporesponsiveness; in primary hyporesponsiveness patients, after one month of treatment with adequate weight-based ESA dose, the target Hb concentration is not achieved; in acquired ESA hyporesponsiveness, after effective treatment with stable ESA dose, achieving the target Hb concentration, the patient requires two consecutive increases (up to 50% beyond the stable dose) in ESA dose. Hyporesponsiveness (also widely referred as resistance) to ESA therapy is associated with a poor outcome, progression of renal disease, sudden death, infectious complications, sudden death and all-cause mortality, mainly due to cardiovascular events in dialysis patients [76][77][78][79]. Several causes are associated with poor response to ESA therapy, including iron deficiency, inflammation, malnutrition and hyperparathyroidism, among others [80][81][82].…”

Relationship between variations in time-dependent response to erythropoiesis-stimulating agents and mortality in hemodialysis patients: a single-center study

“…The conversion ratio adopted in this study was 200 epoetin (EPO):1 darbepoetin-α (DA) [8]. ERI was calculated as the weekly weight-adjusted dose of ESA divided by hemoglobin (Hb) concentration used to evaluate the dose-response effect in ESA treatment as follows [5,6]: ERI (U/kg/week/g per 100 ml) = weekly ESA dose / (weight × Hb). Ascending quartiles of ERI were assessed based on the ERI levels at enrollment, and the ERI quartile groups were as follows: first, <5.1; second, 5.1 to <8.5; third, 8.5 to <13.7; and fourth, ≥ 13.7 U/kg/week/g per 100 ml.…”

“…Lopez-Gomez et al reported finding a relationship between ESA resistance in HD patients and 1-year mortality [4], and ESA resistance remained a significant predictor of mortality in HD patients [5,6]. It appears that resistance to ESA therapy in HD patients could be clinically useful as an index of prognostic marker.…”