Can ferric citrate slow the progression of CKD?

New findings suggest that the administration of ferric citrate might slow the progression of chronic kidney disease (CKD) by lowering the production of fibroblast growth factor 23 (FGF23). This new dietary supplement may also bind to dietary phosphate.

These findings, revealed in a mouse model of chronic CKD, were presented by Connor Francis, MD, PhD, of the Florida University College of Medicine, in an abstract session at the annual meeting of the American Society of Nephrology held October 31 to November 5 in New Orleans, LA. Other investigators involved in the study included Valentin David, PhD, of Northwestern University, and Myles S. Wolf, MD, MMSc, of Duke.

Elevated levels of FGF23 have been shown to be strongly associated with cardiovascular disease, mortality, and progression of CKD, and FGF23 has been shown to be stimulated by elevated phosphate levels and low iron levels. This suggests that reducing dietary phosphate intake or absorption and increasing serum iron may lower FGF23 levels, thereby improving clinical outcomes for patients with CKD.

Researchers fed wild type (WT) mice and Col4a3ko mice with CKD either a 5% ferric citrate–enriched or control diet for 6 weeks. They then performed biochemical, molecular, and histologic analyses. At 10 weeks, the control animals displayed a decline in renal function and signs of iron deficiency anemia. In addition, there was a marked increase in both total FGF23 and intact FGF23 serum levels (P < .05).

In mice that received ferric citrate, serum iron levels were 1.6-fold higher and serum phosphate levels were 1.5-fold lower than controls (P < .05). In addition, total and intact FGF23 were reduced by 4 and 3 fold, respectively, and serum 1,25 vitamin D levels increased 2 fold. The mice in the ferric citrate group also displayed marked improvement in renal function: deceased blood urea nitrogen (BUN, 127 ± 21 vs 218 ± 24 mg/dL) and 24-hour urine albumin (101 ± 69 vs 586 ± 91 µg). Finally, histology revealed reductions in interstitial fibrosis and tubular dystrophy compared with control mice.

An unexpected result of the study was that—even at 6 weeks—there was a significant decrease in BUN and 24-hour urine albumin, noted Francis. "It is quite possible that if we start dietary intervention early enough, we can actually delay the progression of kidney disease," he speculated. However, in response to a question from the audience, Francis was quick to point out that a 5% diet of ferric citrate is well outside the realm of human dosage. Ferric citrate has shown promising results among human subjects at about 0.1% of diet, he said. "This is a proof-of-concept study," Francis explained.

Source: Connor F, Valentin D, Guillaume C, et al. Ferric citrate administration reduces FGF23 production a mouse model of CKD. Presented at: American Society of Nephrology annual meeting, Kidney Week 2017; October 31-November 5, 2017; New Orleans, LA. Oral Presentation 070.