# Phosphate binder therapy and chronic kidney disease in children

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $1,999,823

## Abstract

PROJECT SUMMARY/ABSTRACT
Elevated circulating levels of fibroblast growth factor 23 (FGF23), increased serum phosphate, and anemia are
associated with left ventricular hypertrophy (LVH), cardiovascular disease (CVD), and chronic kidney disease
(CKD) progression in children. Current treatment strategies for CKD-mineral bone disorder and CKD-related
anemia include 1,25D, binders, iron, and erythropoietin stimulating agents (ESA). However, 1,25D therapy
further increases circulating and bone FGF23 levels, and iron deficiency and ESA treatment both also
stimulate FGF23 production. A novel paradigm in earlier CKD has been suggested with the use of phosphate
binders with or without an inhibitor of enteral phosphate absorption, when serum phosphate levels are
within the normal range, to lower FGF23 and to raise endogenous 1,25D levels. However, such approach led
to inconsistent results. Therapy with ferric citrate (FC), on the other hand, has been shown consistently to
lower FGF23 and phosphate levels while improving indices of iron metabolism in adults with CKD stages 3-4.
Furthermore, FC decreased serum phosphate levels, improved iron parameters and was well tolerated in
pediatric dialysis patients. Thus, FC may have added value especially for children with pre-dialysis CKD in
whom iron deficiency anemia and elevated FGF23 levels are highly prevalent. Moreover, iron deficiency is a
potent driver of FGF23 production. Therefore, we hypothesize that treatment with FC will lower intact FGF23
levels during a 12-month period in a randomized, double-blinded, two -arms parallel study in 160 pediatric
patients with CKD stages 3-4 and normal serum phosphate levels. The multi-site trial will pursue the following
specific aims: Specific Aim 1: To determine the efficacy of FC to lower serum intact FGF23 levels (primary
endpoint) in pediatric patients with CKD 3–4 over 12 months. Specific Aim 2: To determine the effects of the
interventions on anemia, kidney function, and indices of bone and mineral metabolism (secondary end-points).
Additionally, we will perform pre- and post-treatment bone biopsies to assess bone histomorphometry and
FGF23 expression in a sub-cohort of 24 UCLA patients. Specific Aim 3: To determine the safety and
tolerability of FC in pediatric CKD 3-4 patients. If our hypothesis is confirmed, then a new treatment paradigm
would emerge in which therapy with FC will be initiated early in CKD, when patients are normophosphatemic,
slowing progressive increases in FGF23 and blunting FGF23-associated adverse renal and CVD.

## Key facts

- **NIH application ID:** 10187559
- **Project number:** 5U01DK122013-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** ISIDRO B. SALUSKY
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,999,823
- **Award type:** 5
- **Project period:** 2020-06-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10187559

## Citation

> US National Institutes of Health, RePORTER application 10187559, Phosphate binder therapy and chronic kidney disease in children (5U01DK122013-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10187559. Licensed CC0.

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