Collins A, Ebben J, Ma J
Frequent IV iron dosing is associated with higher infectious deaths.
ASN 30th Annual Meeting, San Antonio
J Am Soc Nephrol (Sep) 8:190A 1997

In non-uremic patients, high serum iron levels and iron therapy have been associated with increased susceptibility to infections, and iron is a pro-oxidant, which theoretically may increase lipid peroxidation and atherosclerosis. With the new aggressive approach to parenteral iron therapy that is currently being advocated, the importance of understanding potential problems associated with IV iron therapy cannot be underemphasized, thus the value of this retrospective analysis of a large number (33,120) of US hemodialysis patients.

This study examined of death rates, based on frequency of IV iron administration (1-3 months vs 4-6 months). The actual manner in which patients were divided into the low and high groups is not specified in the abstract. Contrary to expectations, the study revealed an 8% higher all cause death rate in the patients being given frequent iron dosing, and a 35% higher infectious cause death rate.

Comment: The main problem with this study is, that it did not capture the reasons why patients were receiving high frequency iron dosing. Presumably, patients with prior lower hematocrit or more refractory anemia were likely to have received more IV iron. Such patients may have had other conditions which could have predisposed them to higher infection and death rates. Specific causes of infection (peripheral vascular disease, pneumonia, vascular access, etc.) may have variable clinical relationship to IV iron therapy, but were not discussed. (Rick L. Latos, M.D., Wheeling, WV)

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ASN 30th Annual Meeting, San Antonio
CRF by problem area : Anemia/Erythropoietin/Iron
CRF by problem area : Infections (other than hepatitis, peritonitis)

The associations of IV iron frequency and infectious mortality, as pointed out by Dr. Latos, cannot distinguish between those who have infectious complications and subsequently receive high frequency iron and the more causal association of patients receiving high frequency iron, which leads to a higher rate of infectious death. The recent article in JASN, May 1998, identifies dialysis catheters as the largest risk for bacteremic episodes in hemodialysis patients. In addition, prior histories of bacteremic episodes are associated with future episodes of bacteremia. Since these important areas of infectious complications, and are identifiable in the claims data, we recently adjusted our analysis to identify hemodialysis patients with dialysis catheter interventions and a history of hospitalization for bacteremia or sepsis. In addition, we not only evaluated the frequency of administration, but looked at the total number of IV iron vials given in the 6 month entry period. We evaluated all-cause, infectious, and cardiac death, as well as the risk of being hospitalized for bacteremia or sepsis. The findings still show that frequent administration (>17 vials delivered over 5 to 6 months) was associated with increased infectious death and increased risk of future hospitalizations for bacteremia and sepsis. In the next phase of our research we will attempt to evaluate only patients who have no infectious comlications in the 6 month entry period. This will require us to identify the other areas outlined by Dr. Latos. In addition, the issues of excessive iron use are still relevant. The recent article in JASN, April 1998, showed that white cell function and bacterial killing was significantly impaired when the ferritin was >650 in patients with an iron saturation <20%. Therefore, continuous dosing of IV iron requires monitoring of serum ferritin levels to maximize the benefit and reduce the risks. Patients with persistent anemia, iron saturations <20%, and ferritins >650 pose a significant challenge. Recent data from Japan has shown that IV vitamin C, at 300 mg 3 times/week over a 4 to 8 week period, has reduced the ferritin levels, and increased the iron saturation and hematocrit levels without a change in EPO dose. This protocol obviously raises concerns about oxalate levels from the vitamin C metabolism. Given the short course of therapy, the oxalate levels did not increase in the Japanese study (Nephrology, 1997). The vitamin C appears to be changing the binding of iron on a tissue level.
Allan Collins, M.D. (acollins@nephrology.org)
Minneapolis, MN - Monday, June 15, 1998 at 07:22:28 (PDT)