Longitudinal trends in serum ferritin levels and associated factors in a national incident hemodialysis cohort.

Taehee Kim,Elani Streja,Steven M. Brunelli,Connie M. Rhee,Yoshitsugu Obi,Kamyar Kalantar-Zadeh,Csaba P. Kovesdy

doi:10.1093/ndt/gfw012

Abstract

The rise in serum ferritin levels among US maintenance hemodialysis patients has been attributed to higher intravenous iron administration and other changes in practice. We examined ferritin trends over time in hemodialysis patients and whether iron utilization patterns and other factors [erythropoietin-stimulating agent (ESA) prescribing patterns, inflammatory markers] were associated with ferritin trajectory. In a 5-year (January 2007–December 2011) cohort of 81 864 incident US hemodialysis patients, we examined changes in ferritin averaged over 3-month intervals using linear mixed effects models adjusted for intravenous iron dose, malnutrition and inflammatory markers. We then examined ferritin trends across strata of baseline ferritin level, dialysis initiation year, cumulative iron and ESA use in the first dialysis year and baseline hemoglobin level. In models adjusted for iron dose, malnutrition and inflammation, mean ferritin levels increased over time in the overall cohort and across the three lower baseline ferritin strata. Among patients initiating dialysis in 2007, mean ferritin levels increased sharply in the first versus second year of dialysis and again abruptly increased in the fifth year independent of iron dose, malnutrition and inflammatory markers; similar trends were observed among patients who initiated dialysis in 2008 and 2009. In analyses stratified by cumulative iron use, mean ferritin increased among groups receiving iron, but decreased in the no iron group. In analyses stratified by cumulative ESA dose and baseline hemoglobin, mean ferritin increased over time. While ferritin trends correlated with patterns of iron use, increases in ferritin over time persisted independent of intravenous iron and ESA exposure, malnutrition and inflammation.

Highlights

As the main storage molecule for iron [1, 2], serum ferritin is a protein related to both iron and oxygen metabolism [3], and it is widely used as a parameter to screen for iron deficiency and overload in chronic kidney disease (CKD) patients [4].Intravenous (IV) iron is one of the most important pharmacotherapies used to treat anemia in CKD patients, and studies have shown that its utilization has substantially increased in most countries over time [5,6,7]
Across the four categories of baseline serum ferritin, ferritin levels increased in parallel over time in models adjusted for case-mix þ malnutrition-inflammation-cachexia syndrome (MICS) covariates as well as those incrementally adjusted for IV iron (Figure 1) and erythropoietin-stimulating agent (ESA) dose (Supplementary data, Appendix Figure S2)
Among a contemporary cohort of >80 000 incident HD patients who were followed for up to 5 years, we found that serum ferritin levels increased sharply in the first year of dialysis treatment followed by more gradual increases from the second year of HD onwards

Summary

Introduction

As the main storage molecule for iron [1, 2], serum ferritin is a protein related to both iron and oxygen metabolism [3], and it is widely used as a parameter to screen for iron deficiency and overload in chronic kidney disease (CKD) patients [4].Intravenous (IV) iron is one of the most important pharmacotherapies used to treat anemia in CKD patients, and studies have shown that its utilization has substantially increased in most countries over time [5,6,7]. In 2012, the Kidney Disease Improving Global Outcomes (KDIGO) group issued updated guidelines on anemia management incorporating some of these changes, which includes consideration of hemoglobin levels when determining the dose of IV iron administration [4]. In parallel with these changes, the United States Renal Data System (USRDS) Annual Data Report showed that mean serum ferritin levels remained stable at $600 ng/mL from 2001 to 2006, but rose to 800 ng/mL in 2011 in prevalent maintenance hemodialysis (HD) patients [9, 10].

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Conclusion