A Pilot Randomized Trial of Ferric Citrate Coordination Complex for the Treatment of Advanced CKD

Significance Statement Evidence suggests that anemia and disordered mineral metabolism (including abnormalities in phosphate and fibroblast growth factor 23 [FGF23]) contribute to adverse outcomes in patients with advanced CKD. To investigate the effects of fixed-dose ferric citrate coordination complex in such patients, the authors randomly assigned 199 patients with eGFR<20 ml/min per 1.73 m 2 2:1 to ferric citrate coordination complex or usual care. Treatment with ferric citrate coordination complex significantly increased hemoglobin, ferritin, and transferrin saturation and significantly reduced FGF23, while maintaining serum phosphate in the normal range in the majority of patients. It also significantly reduced use of erythropoiesis-stimulating agents and intravenous iron, hospital admissions, hospital days, and time to the composite end point of death, provision of dialysis, or kidney transplantation. These findings support the conduct of a placebo-controlled trial using ferric citrate coordination complex in advanced CKD. Background Researchers have yet to determine the optimal care of patients with advanced CKD. Evidence suggests that anemia and CKD–related disordered mineral metabolism (including abnormalities in phosphate and fibroblast growth factor 23 [FGF23]) contribute to adverse outcomes in this population. Methods To investigate whether fixed-dose ferric citrate coordination complex favorably affects multiple biochemical parameters in patients with advanced CKD, we randomly assigned 203 patients with eGFR≤20 ml/min per 1.73 m 2 2:1 to receive a fixed dose of ferric citrate coordination complex (two tablets per meal, 210 mg ferric iron per tablet) or usual care for 9 months or until 3 months after starting dialysis. No single biochemical end point was designated as primary; sample size was determined empirically. Results The two groups had generally similar baseline characteristics, although diabetes and peripheral vascular disease were more common in the usual-care group. Ferric citrate coordination complex significantly increased hemoglobin, transferrin saturation, and serum ferritin, and it significantly reduced serum phosphate and intact FGF23 ( P <0.001 for all). Of the 133 patients randomized to ferric citrate coordination complex, 31 (23%) initiated dialysis during the study period, as did 32 of 66 (48%) patients randomized to usual care ( P =0.001). Compared with usual care, ferric citrate coordination complex treatment resulted in significantly fewer annualized hospital admissions, fewer days in hospital, and a lower incidence of the composite end point of death, provision of dialysis, or transplantation ( P =0.002). Conclusions The beneficial effects of fixed-dose ferric citrate coordination complex on biochemical parameters, as well as the exploratory results regarding the composite end point and hospitalization, suggest that fixed-dose ferric citrate coordination complex has an excellent safety profile in an unselected population with advanced CKD and merits further study.