DENVER—Hemodialysis (HD) patients may be receiving excessive intravenous (IV) iron that could contribute to iron overload and toxicity in the long term, new data suggest.

A team led by Ajay K. Singh, MD, of Brigham and Women’s Hospital in Boston, evaluated whether withholding iron in HD patients for up to 26 weeks while keeping the ESA dose nearly constant leads to iron-restricted erythropoiesis. The study included 26 patients (mean age of 58 years) who were in the placebo arm of a double-blind, randomized study of soluble ferric pyrophosphate, an investigational, physiologic, soluble, non-carbohydrate iron salt that donates iron to transferrin via dialysate, bypassing the reticuloendothelial system. Twenty-one patients treated with mean weekly ESA doses of 12,510 U/week epoetin or 59 µg/week darbepoetin had all oral and IV iron discontinued. Ferritin levels decreased from an average of 503 µg/L at baseline to 394 µg/L at the end of the study, a statistically significant decrease of 22% that suggests mobilization of iron from iron stores. The study revealed no significant change in transferrin saturation, hemoglobin (Hb), or cellular Hb in reticulocytes, suggesting that stored iron was sufficient to maintain erythropoiesis, the researchers concluded.

HD-related iron loss is about 5-7 mg per dialysis session (or about 1 gram per year).  Most HD patients receive regular IV iron in excess of actual iron losses (median dose 4.2 grams per year, according to data from the U.S. Renal Data System). The investigators explain that IV iron stimulates hepcidin, which blocks release of iron from the reticuloendothelial system, limiting iron availability to the erythron and causing progressive buildup of iron in tissue stores.

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The clinical trial data heightens the concern raised by the Kidney Disease Outcome Quality Initiative that a mean ferritin level of 500 µg/L may in fact represent a state of tissue iron excess, Dr. Singh said. Consequently, he and his colleagues believe that a therapeutic strategy liberalizing IV iron administration and targeting higher serum ferritin levels to reduce ESA utilization may further aggravate the state of iron overload.