The Importance of Iron in Long-Term Survival of Maintenance Hemodialysis Patients Treated With Epoetin-Alpha and Intravenous Iron: Analysis of 9.5 Years of Prospectively Collected Data

Victor E. Pollak; Jonathan A. Lorch; Rakesh Shukla; Supriya Satwah

Disclosures

BMC Nephrology 

In This Article

Abstract and Background

Abstract

Background: In patients treated by maintenance hemodialysis the relationship to survival of hemoglobin level and administered epoetin-alfa and intravenous iron is controversial. The study aim was to determine effects on patient survival of administered epoetin-alfa and intravenous iron, and of hemoglobin and variables related to iron status.
Methods: The patients were 1774 treated by maintenance hemodialysis in 3 dialysis units in New York, NY from January 1998 to June, 2007. A patient-centered, coded, electronic patient record used in patient care enabled retrospective analysis of data collected prospectively. For survival analysis, patients were censored when transplanted, transferred to hemodialysis at home or elsewhere, peritoneal dialysis. Univariate Kaplan-Meier analysis was followed by multivariate analysis with Cox's regression, using as variables age, race, gender, major co-morbid conditions, epoetin-alfa and intravenous iron administered, and 15 laboratory tests.
Results: Median age was 59 years, epoetin-alfa (interquartile range) 18,162 (12,099, 27,741) units/week, intravenous iron 301 (202, 455) mg/month, survival 789 (354, 1489) days. Median hemoglobin was 116 (110, 120)g/L, transferrin saturation 29.7 (24.9, 35.1)%, serum ferritin 526 (247, 833) μg/L, serum albumin 39.0 (36.3, 41.5) g/L. Survival was better the higher the hemoglobin, best with > 120 g/L. Epoetin-alfa effect on survival was weak but had statistically significant interaction with intravenous iron. For intravenous iron, survival was best with 1–202 mg/month, slightly worse with 202–455 mg/month; it was worst with no intravenous iron, only slightly better with > 455 mg/month. Survival was worst with transferrin saturation ≤ 16%, serum ferritin ≤ 100 μg/L, best with transferrin saturation > 25%, serum ferritin > 600 μg/L The effects of each of hemoglobin, intravenous iron, transferrin saturation, and serum ferritin on survival were independently significant and not mediated by other predictors in the model.
Conclusion: Long term survival of maintenance hemodialysis patients was favorably affected by a relatively high hemoglobin level, by moderate intravenous iron administration, and by indicators of iron sufficiency. It was unfavorably influenced by a low hemoglobin level, and by indicators of iron deficiency.

Background

Deficiencies of erythropoietin and iron play a role in genesis of the anemia of Chronic Kidney Disease (CKD) and End Stage Renal Disease (ESRD) patients treated by hemodialysis (HD). Both are correctible. Although treatment with epoetin-alfa (EPO) and newer erythrocyte stimulating agents (ESA) has mitigated its severity, some recent studies have reported adverse outcomes of effective anemia correction with EPO and other ESAs.[1,2,3]

Iron deficiency anemia is prevalent in 2–8% of adult women,[4] latent iron deficiency (i.e., without anemia) may be twice as frequent.[5] In a complex, stratified random US population sample of 15,387 subjects, anemia (hemoglobin < 110 g/L in women, < 120 g/L in men) was found in 569 (3.9%), in 179 of whom creatinine clearance was < 50 ml/min. Of these, < 33% were iron sufficient (TSAT ≥ 20%, serum ferritin ≥ 100 μg/L).[6] Thus iron deficiency and iron deficiency anemia are highly prevalent in renal insufficiency even before dialysis is required. Recent studies have confirmed this,[2,7,8,9,10,11] and intravenous (IV) iron replenishment slowed deterioration of renal function in CKD.[7,8]

Possible adverse effects of raising hemoglobin (Hb) concentration to > 120 g/L on patient survival have attracted wide attention recently, and have resulted in warnings about the practice. The importance of adequate iron availability was stressed in the earliest EPO studies in HD patients,[12] yet few reports on the effects of EPO and newer ESAs have explicitly addressed the need of patients for adequate iron,[2,3,10] and ESA effects have been tested in CKD patients at least 25–30% of whom had evidence of iron deficiency at study start before the ESA was given.[2,3,10] Also, widely publicized guidelines suggesting adverse effects of serum ferritin levels > 500–1,000 μg/L[13,14,15,16] have cautioned about IV iron usage.

We recently reported the effect of a particular patient-centered electronic patient record (EPR) on mortality in 1,790 patients treated by in-center HD in 3 dialysis units over 7–9 years.[17] That analysis was limited in at least two respects. First, patient mortality was the measured outcome; second, the effect of various prognostic factors on mortality was assessed one predictor at a time. Here, we apply univariate and multivariate methods to examine the effects of various factors, including EPO and IV iron administration, on patient survival. The data analyzed were those collected prospectively during patient care, using the EPR, from 1998 onward. We report on long-term survival of these patients in relation to anemia and its management with EPO and IV iron.

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