The safety of achieved iron stores and their effect on IV iron and ESA use: post-hoc results from a randomized trial of ferric citrate as a phosphate binder in dialysis .

Abstract

Iron stores assuring optimal efficacy/safety for erythropoiesis are unknown in the dialysis population. Using multicenter trial data, we related safety profiles, erythropoiesis-stimulating agent (ESA), and intravenous iron dosing to achieved iron stores in 441 subjects randomized 2:1 to ferric citrate or active control as their phosphate binder over 52weeks. Intravenous iron was given at each site's discretion if ferritin ≤1,000ng/mL and transferrin saturation ≤30%. Multivariable time-dependent Cox regression jointly related the primary safety outcome (composite of cardiac, infection, gastrointestinal, and hepatobiliary serious adverse events) to moving averages of ferritin and transferrin saturation over the preceding 90days with covariate adjustment. Multivariable generalized estimating equations related elevated ESA and intravenous iron doses to trailing 90-day averages of ferritin and transferrin saturation with covariate adjustment. The adjusted hazard ratio for the safety composite per 10% increase in transferrin saturation was 0.84 (95% confidence interval 0.68-1.02, p=0.08) and 1.09 (0.86-1.35, p=0.48) per 400ng/mL increase in ferritin. The adjusted hazard ratio for the safety composite was 0.50 (0.29-0.88, p=0.016) for the highest transferrin saturation tertile vs. the lowest. Adjusted odds ratios for higher intravenous iron dose were lower in the highest (0.23 [0.16-0.35], p<0.001) and middle transferrin saturation tertile (0.42 [0.31-0.57], p<0.001) vs. lowest. Incidence of elevated ESA dose was lower in the highest transferrin saturation tertile (p=0.01). Ferritin did not predict clinical events or ESA dose. Transferrin saturation may be a better marker than serum ferritin to judge optimal iron stores in dialysis patients. Transferrin saturations >34% are safe and provide maximal efficacy. .