Dietary and Pharmacological Modification of Fibroblast Growth Factor-23 in Chronic Kidney Disease

作者:Adema Aaltje Y*; de Borst Martin H; ter Wee Piet M; Vervloet Marc G
来源:Journal of Renal Nutrition, 2014, 24(3): 143-150.
DOI:10.1053/j.jrn.2013.09.001

摘要

Increased levels of phosphorus and fibroblast growth factor-23 (FGF-23) are strong predictors of cardiovascular morbidity and mortality. From a physiological perspective and supported by some data, phosphorus is the main driver for FGF-23 secretion. Therefore, it is conceivable that interventions aiming at restriction of phosphorus uptake from the gastrointestinal tract may lower serum FGF-23 levels and improve cardiovascular risk and subsequently survival. It is not currently known to what extend phosphorus and FGF-23 are independent risk factors, and therefore both need to be targeted. However, their respective metabolisms are tightly connected. Control of phosphorus levels in chronic kidney disease (CKD) patients is attempted mainly by restriction of dietary intake and the use of phosphorus binders. In this review, it is outlined that not just the amount of dietary phosphorus intake is important but also its type (organic vs. inorganic), its source (animal vs. plant derived), and the protein-to-phosphorus ratio in the bioavailability of phosphorus from food. This qualitative aspect of diet is likely a neglected aspect of dietary counseling in CKD. However, in more advanced stages of CKD, dietary restriction of phosphorus alone is usually not sufficient to control hyperphosphatemia, and phosphorus binders are indicated. The inexpensive, calcium-containing dietary phosphorus binders are used commonly worldwide. However, they are not suitable for every patient because of the association with elevated serum calcium, increase in vascular and valvular calcification scores, and cardiovascular and all-cause mortality. The calcium content itself in these binders has recently been implicated to upregulate FGF-23. For that reason, the noncalcium, aluminum-free agents such as sevelamer and lanthanum are being advocated. However, these drugs do not have a clearly defined effect on circulating levels of FGF-23. Although it is conceivable that targeting FGF-23 may lead to improved clinical outcomes, this remains speculative. Therefore, more studies are needed to answer the question if this can be achieved with any of the phosphorus binders, or by another (additional) pharmacological intervention.

  • 出版日期2014-5