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

Abstract

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/1.73m

2015 Japanese Society for Dialysis Therapy: Guidelines for Renal Anemia in Chronic Kidney Disease

“…A study examining predialysis CKD patients has revealed that high TSAT is associated with a decrease in GFR and that the mortality rate tends to increase in patients with advanced CKD with serum ferritin levels ≥250 ng/mL [140].…”

Disordered Iron Homeostasis in Chronic Heart Failure

“…Even in the absence of anemia, iron deficiency is a potent substrate for dyspnea and exercise intolerance (26,27) and identifies those in the general population at a heightened risk for mortality (28). In patients with uremia, lower levels of transferrin saturation (TSAT), a more reliable marker of iron deprivation than ferritin in inflammatory cohorts, also correlate to poorer survival (29). Whether lower TSAT relates to mortality independently and more powerfully than anemia in CHF remains unclear.…”

The Anemia of Heart Failure

“…Recently, in CKD patients not on dialysis, it was found that the lower the %Tf Sat the higher the mortality, again raising the possibility that iron deficiency may be a common and reversible cause of severe cardiovascular disease [63]. Although there has been concern about increased iron stores being associated with increased risk of coronary heart disease [64], this has not been confirmed by some recent studies [65] and the issue is still controversial.…”