Spikes in serum ferritin within the first 6 months of starting maintenance hemodialysis (HD) are associated with worse all-cause mortality, a new study finds.

Kamyar Kalantar-Zadeh, MD, MPH, PhD, of the University of California-Irvine School of Medicine in Orange, California, and colleagues used 2007–2011 data from an administrative database to study the change in serum ferritin in quintiles from the first to second quarter after HD initiation for 93,979 outpatients. Compared with patients who had relatively stable serum ferritin (100 ng/mL decrease to less than 100 ng/mL increase per quarter), patients who experienced an abrupt rise of 400 ng/mL per quarter or more had a 7%, 17%, 26%, and 49% higher risk of all-cause mortality when baseline serum ferritin levels were less than 200, 200 to less than 500, 500 to less than 800, and 800 ng/mL or greater, respectively.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2012 clinical practice guidelines for anemia recommend intravenous (IV) iron administration in HD patients with serum ferritin levels at or below 500 ng/mL. “These findings suggest that a more cautious approach in selecting patients needing IV iron treatment may be appropriate,” Dr Kalantar-Zadeh and his team stated in the American Journal of Nephrology (2017;46:120-130).

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The investigators explained that serum ferritin, which reflects body iron storage, is influenced by inflammatory conditions in addition to oral or IV iron dose and dietary iron. Other unknown factors may also affect ferritin.

The mortality risk associated with a rise in serum ferritin was “robust” regardless of IV iron dose. Iron saturation, a marker of iron deficiency or overloading, also appeared to have no independent effect on mortality. An increase of serum ferritin of 100 ng/mL/quarter or more was associated with early death, whether iron saturation rose or fell.

Using multivariable models, the team adjusted for malnutrition-inflammation cachexia syndrome (MICS), IV iron, erythropoiesis-stimulating agent (ESA) doses, as well as sociodemographic factors. They lacked data on C-reactive protein and interleukin-6, however. Only a small proportion of HD patients avoided IV iron, limiting comparative analyses. Future studies exploring possible mechanisms between rising ferritin, IV iron, and mortality are needed.

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Kim T, Streja E, Soohoo M, et al. Serum Ferritin Variations and Mortality in Incident Hemodialysis Patients. Am J Nephrol 2017;46:120–130. doi: 10.1159/000478735