Work

Lb05randomized Trial of the Effects of Ferric Citrate in Patients With Advanced Chronic Kidney Disease

Year: 2018

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: INTRODUCTION AND AIMS: We hypothesized that provision of fixed dose ferric citrate to patients with advanced chronic kidney disease, independent of serum phosphate or degree of anemia, would improve multiple biochemical aspects simultaneously and reduce the need for exogenous ESA or intravenous iron. METHODS: Patients with eGFR ≤ 20 ml/min and who were not anticipated to start RRT within 8 weeks were randomized 2:1 to received fixed dose ferric citrate((FC, 210 mg, two per meal) or standard of care treatment (SOC). 203 patients were randomized and 199 attended at least 1 follow up visit. Patients were seen monthly for 9 months, or, for individuals who started hemodialysis or peritoneal dialysis, for 3 months thereafter. RESULTS: 133 patients received FC and 66 received SOC. There were a higher proportion of diabetic patients in the SOC arm while other baseline characteristics were similar. 37% of patients in the SOC arm received P binders during the non-dialysis period. 30 patients assigned to FC(23%) and 31 patients assigned to SOC (47%) initiated HD/PD. Select baseline and on-study laboratory variables of interest are shown in Table 1. As compared to the SOC arm, treatment with FC resulted in statistically significant increases in mean TSAT, ferritin, and hemoglobin and statistically significant reductions in mean serum phosphate, and intact FGF23. Patients randomized to FC were significantly less likely to receive ESA or intravenous iron however after adjusting for baseline characteristics, reduction in ESA use was of borderline statistical significance (p=0.06) while use of intravenous iron remained significantly reduced (p=0.006). Cumulative doses of ESA and IV iron were reduced in those receiving FC. The risk of RRT or death was significantly reduced with FC in the total cohort and among the diabetic sub-group (p=0.049 and p=0.045 respectively, Figure 1). MMRM analysis demonstrated a modest but significant difference between change in the slope of eGFR between FC and SOC treatment arms (p=0.049). CONCLUSIONS: Administration of fixed dose ferric citrate to patients with advanced chronic kidney disease, regardless of entry serum phosphate, hemoglobin or iron sufficiency led to statistically significant increases in TSAT, ferritin, and hemoglobin, significant reductions in serum phosphate and intact-FGF23, and reduced the exposure to ESA and intravenous iron prior to dialysis. There is a suggestion of benefit on time to death, dialysis or transplant for those assigned to FC even among the diabetic sub-group. These findings provide strong rationale for a larger, randomized, placebo-controlled trial of FC to optimize care in advanced CKD.

Source: Nephrology Dialysis Transplantation

DOI: 10.1093/ndt/gfy146.lb05