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

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.Iron is an essential trace element which plays an important role in the catalysis of oxidative reactions and in the transport of soluble gases (1). Assessment of iron stores is done routinely in everyday nephrology practice (2), through measurement of total iron saturation (ISAT; also known as transferrin saturation) and serum ferritin (3).Iron deficiency is common in patients with nondialysis-dependent chronic kidney disease (NDD-CKD) (4,5), but it is unclear to what extent levels of ISAT and ferritin are associated with outcomes in this population. Examining hard endpoints is especially important given the concern that exceeding certain limits of ISAT or ferritin may be deleterious through excess iron deposition and induction of oxidative stress (6–9). We examined the associations of these iron markers with all-cause mortality, the composite of predialysis mortality or ESRD, and the slopes of estimated GFR (eGFR) in 453 men with moderate and advanced NDD-CKD.