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Association of Markers of Iron Stores with Outcomes in Patients with Nondialysis-Dependent Chronic Kidney Disease

Csaba P. Kovesdy^*,, Wilber Estrada, Shahram Ahmadzadeh^*,, and Kamyar Kalantar-Zadeh^,||

^* Division of Nephrology, Salem Veterans Affairs Medical Center, Salem, Virginia; Department of Medicine, University of Virginia, Charlottesville, Virginia; Department of Medicine, Carilion Clinic, Roanoke, Virginia; Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California; ^|| David Geffen School of Medicine at UCLA, Los Angeles, California

Correspondence: Dr. Csaba P Kovesdy, FASN, CPIm, Division of Nephrology, Salem Veteran Affairs Medical Center, 1970 Roanoke Boulevard, Salem, VA 24153. Phone: 540-982-2463; Fax: 540-224-1963; E-mail: csaba.kovesdy{at}va.gov

Background and objectives: Assessments of iron stores by serum iron saturation ratio (ISAT) and ferritin are used to direct anemia therapy in chronic kidney disease (CKD) and are associated with clinical outcomes in patients on dialysis. The association of ISAT and ferritin with outcomes in patients with nondialysis-dependent CKD (NDD-CKD) has not been studied.

Design, setting, participants, & measurements: All-cause mortality and progression of CKD [slopes of estimated GFR (eGFR)] were examined in 453 men with NDD-CKD. Mortality and the composite of mortality and ESRD were studied in Cox models. Slopes of eGFR were examined in mixed-effects models.

Results: Lower ISAT was associated with higher mortality; adjusted hazard ratio [95% confidence interval (CI)] with ISAT of <12%, 13 to 17%, and >23% versus 18 to 23%; 1.40 (0.99 to 1.98), 1.20 (0.82 to 1.76), and 0.97 (0.67 to 1.41), P = 0.025 for trend. ISAT was also associated with steeper slopes of eGFR (one log-unit higher ISAT associated with a slope of –0.89 ml/min/1.73m² /yr (95% CI: –1.75, –0.02, P = 0.044). Serum ferritin level showed no significant association with outcomes overall, but a trend for higher mortality was observed in patients with a serum ferritin level >250 ng/ml.

Conclusions: Higher ISAT is associated with lower mortality and with more progressive CKD. Clinical trials are needed to examine if correction of low iron levels can improve mortality without affecting kidney function in NDD-CKD.