Phosphate Binder Therapy and Chronic Kidney Disease in Children

We propose to conduct a 12-month, double-blind, randomized, placebo-controlled trial to assess the effects of therapy with ferric citrate (FC) on changes in intact FGF23 levels (iFGF23) (primary endpoint) in 160 pediatric patients (80 in each of the two arms) aged 6–17 years of either sex with CKD stages 3–4 and age-appropriate normal serum phosphate levels. Participants will be randomized to one of the two groups: 1) ferric citrate or 2) ferric citrate placebo. Patients will be recruited from twelve core clinical sites. The proposed U01 will provide the infrastructure to pursue the following Specific Aims and aligned Hypotheses: Specific Aim 1: To determine the efficacy of FC to lower iFGF23 levels (primary endpoint) in pediatric patients with CKD stages 3–4 over 12 months. Hypothesis 1: Compared to placebo, active treatment with FC will lower iFGF23 levels. Specific Aim 2: To determine the effects of FC on anemia, kidney function, and indices of mineral and bone metabolism (secondary endpoints) in pediatric patients with CKD stages 3–4 over 12 months: Anemia: Determine the effects of FC on indices of iron metabolism and the need for initiation of iron therapy and/or erythropoietin stimulating agents (ESAs). Hypothesis 2: Compared to placebo, active therapy with FC will prevent the development of anemia and will delay the use or decrease the amount of ferrous sulfate and/or ESAs. Kidney function: Determine the effects of FC on the rate of decline in GFR. . Hypothesis 3: Compared to placebo, active treatment with FC will slow the progressive decline in GFR. Indices of Mineral and Bone metabolism: Determine the effects of FC on biochemical indices of bone and mineral metabolism. Additionally, determine the effects of FC on bone mineralization and bone expression of FGF23 in a sub-cohort of UCLA patients (n=24) who will undergo pre- and post-treatment bone biopsies. Hypothesis 4: Compared to placebo, active treatment with FC will delay the development of secondary hyperparathyroidism, reduce markers of bone turnover, and decrease bone production of FGF23. Specific Aim 3: To determine the safety and tolerability of FC in pediatric patients with CKD 3–4. Hypothesis 5: Therapy with FC will be safe, well-tolerated, and acceptable.