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

Abstract

BackgroundResearchers 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. ResultsThe 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). ConclusionsThe 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.

FGF23 and Phosphate–Cardiovascular Toxins in CKD

“…Recent studies indicate beneficial effects of ferric citrate treatment for CKD patients [157,158,159]. Block et al showed in a placebo-controlled clinical trial in non-dialysis CKD patients that ferric citrate significantly reduces intact FGF23 and serum phosphate levels among patients with elevated baseline phosphate (≥4.5 mg/dL).…”

“…The treatment did not affect phosphate levels in patients with lower baseline serum phosphate levels [157]. Besides controlling phosphate and FGF23 levels, ferric citrate may have beneficial effects on CKD-related anemia by increasing hemoglobin, ferritin, and transferrin saturation [158]. As shown by Francis et al, ferric citrate not only reduces FGF23 and phosphate levels, but also improves the renal and cardiac function in the Col4a3 knockout mouse model of progressive CKD.…”

Ferric citrate: cardio- and renoprotective in chronic kidney disease?

“…Recently, a single-center exploratory pilot study was conducted in which 199 patients with advanced CKD (estimated glomerular filtration rate < 20 ml/min per 1.73 m 2 ) were randomized to a fixed dose of ferric citrate versus usual care. 7 Ferric citrate use was associated with increased transferrin saturation, increased hemoglobin, decreased serum phosphate concentrations, and decreased circulating intact FGF23 levels. The ferric citrate group also had a lower incidence of a composite endpoint that included death, provision of dialysis, or transplantation.…”

“…The improved biochemical profiles observed in the present murine study mirror those seen in human trials of ferric citrate. 1,7 However, it remains to be proven whether ferric citrate use in patients with CKD will improve clinical outcomes. Recently, a single-center exploratory pilot study was conducted in which 199 patients with advanced CKD (estimated glomerular filtration rate < 20 ml/min per 1.73 m 2 ) were randomized to a fixed dose of ferric citrate versus usual care.…”

Conventional and novel impacts of ferric citrate on iron deficiency anemia and phosphorus metabolism in rats

“…From these clinical results mentioned above, there is a possibility that ferric citrate could exert not only phosphate reducing effect but also hematopoietic effect in advanced CKD patients. It is expected that, in theory, successful treatment of hyperphosphatemia and anemia in patients with CKD could help avoid adverse clinical outcomes; [2] however, with the exception of renal replacement, no interventions have yet been proven to improve outcomes.…”