Title: Moderately high serum ferritin concentration is not a sign of iron overload in dialysis patients
Abstract: To the Editor: The review of Eschbach and Adamson1.Eschbach J.W. Adamson J.W. Iron overload in renal failure patients: changes since the introduction of erythropoietin therapy.Kidney Int. 1999; 55: S-35-S-43Google Scholar maintained that increased serum ferritin concentration is a sign of iron overload and a risk factor for infection in dialysis patients. Whereas a low serum ferritin level is reported to be highly specific in diagnosing iron deficiency2.Kalantar-Zadeh K. Hoffken B. Wunsch H. Fink H. Kleiner M. Luft F.C. Diagnosis of iron deficiency anemia in renal failure patients during the post-erythropoietin era.Am J Kidney Dis. 1995; 26: 292-299Abstract Full Text PDF PubMed Scopus (167) Google Scholar, the accuracy of a high serum ferritin level to diagnose iron overload has been questioned. In a previous study2.Kalantar-Zadeh K. Hoffken B. Wunsch H. Fink H. Kleiner M. Luft F.C. Diagnosis of iron deficiency anemia in renal failure patients during the post-erythropoietin era.Am J Kidney Dis. 1995; 26: 292-299Abstract Full Text PDF PubMed Scopus (167) Google Scholar, we examined bone marrow iron stores (scored 0 to 4+) in 24 uremic patients and showed that serum ferritin values were significantly lower only in patients with completely depleted bone marrow (score zero), while four other groups had similar ferritin levels Figure 1a. The average bone marrow iron scores in four ferritin “quartiles” were exceptionally low in the lowest quartile but no difference was observed among the other three higher quartiles Figure 1b. Pearson correlation coefficients of log ferritin and transferrin, albumin, and C-reactive protein (CRP) were -0.72, -0.54 and +0.41, respectively (P < 0.05). These results denote that a high serum ferritin is not a reliable indicator of iron overload, but may instead represent an acute phase reactant as reflected by increased CRP. Recently, Gunnell et al showed that erythropoietin resistance occurred in the context of high ferritin and low transferrin levels, the pattern expected in the acute-phase response, not in iron overload3.Gunnell J. Yeun J.Y. Depner T.A. Kaysen G.A. Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients.Am J Kidney Dis. 1999; 33: 63-72Abstract Full Text Full Text PDF PubMed Scopus (282) Google Scholar. We showed that sick, malnourished, dialysis patients had an increased serum ferritin and decreased transferrin levels and required higher doses of erythropoietin4.Kalantar-Zadeh K. Kleiner M. Dunne E. Ahern K. Nelson M. Koslowe R. Loft F.C. Total iron-binding capacity-estimated transferrin correlates with the nutritional subjective global assessment in hemodialysis patients.Am J Kidney Dis. 1998; 31: 263-272Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar. More recently, we found that increased serum ferritin is a predictor of mortality in dialysis patients and has a relative risk of death of 1.80 (95% CI: 1.04–3.11) (abstract; Kalantar-Zadeh K et al., Am J Kidney Dis 33:A30, 1997. Thus, the impression that an increased serum ferritin is a risk factor for infection might be flawed and based on cross-sectional observations that confirm a strong “association” between serum ferritin and the degree of “sickness” without any proof of a “cause-effect” relationship. Therefore, iron stores should not be evaluated solely on the basis of serum ferritin and abnormally high serum ferritin concentrations may not be a reliable indication for withholding iron administration in uremic patients.