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Combined High Serum Ferritin and Low Iron Saturation in Hemodialysis Patients: The Role of Inflammation

Mehdi Rambod^*,, Csaba P. Kovesdy, and Kamyar Kalantar-Zadeh^*,

^* Harold Simmons Center for Kidney Disease Research and Epidemiology and Division of Nephrology and Hypertension, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California; and Salem Veterans Affairs Medical Center, Salem, Virginia

Correspondence: Dr. Kamyar Kalantar-Zadeh, Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, C1-Annex, Torrance, CA 90502. Phone: 310-222-3891; Fax: 310-782-1837; E-mail: kamkal{at}ucla.edu

Background: Serum ferritin, frequently used as a marker of iron status in individuals with chronic kidney disease, is also an inflammatory marker. The concurrent combination of high serum ferritin and low iron saturation ratio (ISAT) usually poses a diagnostic dilemma. We hypothesized that serum ferritin 500 ng/ml, especially in the seemingly paradoxical presence of ISAT level <25%, is more strongly associated with inflammation than with iron in maintenance hemodialysis (MHD) patients.

Design, setting, and participants: In 789 MHD patients in the Los Angeles area, the association of serum ferritin 500 ng/ml with inflammatory markers, including IL-6 (IL-6) and C-reactive protein levels, and malnutrition-inflammation score (MIS) was examined.

Results: After multivariate adjustment for case-mix and other measures of malnutrition-inflammation complex, MHD patients with serum ferritin 500 ng/ml and ISAT <25% had higher odds ratio for serum C-reactive protein 10 mg/L. The area under the receiver operating characteristic curves for the continuum of ISAT and IL-6 in detecting a serum ferritin 500 ng/ml were identical (0.57 versus 0.56, P = 0.7). The combination of IL-6 with ISAT yielded a higher area under the receiver operating characteristic curve (0.61) than either ISAT or IL-6 alone (P = 0.03 and P = 0.02, respectively).

Conclusion: In MHD patients, ferritin values above 500 ng/ml, especially in paradoxical conjunction with low ISAT, are associated with inflammation. Strategies to dissociate inflammation from iron metabolism to mitigate the confounding impact of inflammation on iron and to improve iron treatment responsiveness may improve anemia management in chronic kidney disease.

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