Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKD

• Published in: Journal of the American Society of Nephrology Vol. 26; no. 10; pp. 2328 - 2339
• Main Authors: Isakova, Tamara, Ix, Joachim H, Sprague, Stuart M, Raphael, Kalani L, Fried, Linda, Gassman, Jennifer J, Raj, Dominic, Cheung, Alfred K, Kusek, John W, Flessner, Michael F, Wolf, Myles, Block, Geoffrey A
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 01.10.2015
• Subjects: Fibroblast Growth Factors - antagonists & inhibitors; Fibroblast Growth Factors - metabolism; Humans; Phosphates - antagonists & inhibitors; Phosphates - metabolism; Renal Insufficiency, Chronic - drug therapy; Renal Insufficiency, Chronic - metabolism; Up Front Matters; phosphate binders; chronic kidney disease; phosphate uptake
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.2015020117

Patients with CKD often progress to ESRD and develop cardiovascular disease (CVD), yet available therapies only modestly improve clinical outcomes. Observational studies report independent associations between elevated serum phosphate and fibroblast growth factor 23 (FGF23) levels and risks of ESRD, CVD, and death. Phosphate excess induces arterial calcification, and although elevated FGF23 helps maintain serum phosphate levels in the normal range in CKD, it may contribute mechanistically to left ventricular hypertrophy (LVH). Consistent epidemiologic and experimental findings suggest the need to test therapeutic approaches that lower phosphate and FGF23 in CKD. Dietary phosphate absorption is one modifiable determinant of serum phosphate and FGF23 levels. Limited data from pilot studies in patients with CKD stages 3-4 suggest that phosphate binders, low phosphate diets, or vitamin B3 derivatives, such as niacin or nicotinamide, may reduce dietary phosphate absorption and serum phosphate and FGF23 levels. This review summarizes current knowledge regarding the deleterious systemic effects of phosphate and FGF23 excess, identifies questions that must be addressed before advancing to a full-scale clinical outcomes trial, and presents a novel therapeutic approach to lower serum phosphate and FGF23 levels that will be tested in the COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE study.