Predictors of iron versus erythropoietin responsiveness in anemic hemodialysis patients

Abstract

Anemia protocols for hemodialysis patients usually titrate erythropoietin (ESA) according to hemoglobin and iron according to a threshold of ferritin, with variable response seen. A universally optimum threshold for ferritin may be incorrect, and another view is that ESA and iron are alternative anemia treatments, which should be selected based on the likely response to each. Hemodialysis patients developing moderate anemia were randomised to treatment with either an increase in ESA or a course of intravenous iron. Over 2423 patient-months in 197 patients, there were 133 anemia episodes with randomized treatment. Treatment failure was seen in 20/66 patients treated with ESA and 20/67 patients treated with iron (30.3 vs. 29.9%, p = 1.0). Successful ESA treatment was associated with lower C-reactive protein (13.5 vs. 28.6 mg/L, p = 0.038) and lower previous ESA dose (6621 vs. 9273 μg/week, p = 0.097). Successful iron treatment was associated with lower reticulocyte hemoglobin (33.8 vs. 35.5 pg, p = 0.047), lower hepcidin (91.4 vs. 131.0 μg/ml, p = 0.021), and higher C-reactive protein (29.5 vs. 12.6 mg/L, p = 0.085). A four-variable iron preference score was developed to indicate the more favorable treatment, which in a retrospective analysis reduced treatment failure to 17%. Increased ESA and iron are equally effective, though treatment failure occurs in almost 30%. Baseline variables including hepcidin can predict treatment response, and a four-variable score shows promise in allowing directed treatment with improved response rates.

Keywords: anemia; hemodialysis; hepcidin; iron.

FIGURE 1

Patient flow through the study. The number of participants is provided at each stage and reasons for exclusion from analysis

FIGURE 2

Hemoglobin response by randomization group. Participants continuing in the study, with inadequate response at 2 months, received crossover treatment, and are represented in months 2–4

FIGURE 3

Baseline predictors in responders and non‐responders. Erythropoietin responders had lower baseline CRP and EPO dose, whereas iron responders had lower hepcidin, Tsat and Ret‐Hb, and higher CRP

FIGURE 4

Response observed by threshold of iron score. Higher iron score predicts a more favorable response to iron than erythropoietin. In this model, iron is given to those with iron score > = threshold, erythropoietin is given otherwise, with outcomes estimated by retrospective analysis of the group. At a low threshold (left of the chart) almost all receive iron with around 30% non‐response. Moving to the right as threshold increases, iron is given to smaller proportion of patients but the non‐response rate is reduced. The same is true for erythropoietin moving from right to left of the chart. Using a threshold of 6, overall non‐response (middle two categories) was seen in 12.4%