KLOTHO

An adequate phosphate balance is essential for the maintenance of skeletal growth, development and function. It is also crucial in basic cellular functions, ranging from cell signaling to energy metabolism. Bone-derived fibroblast growth factor 23 (FGF23), through activating FGF receptor system, plays an important role in the systemic regulation of phosphate metabolism. Under physiological conditions, FGF23 exerts serum phosphate-lowering effects by inducing urinary phosphate excretion. Increased FGF23 activities are associated with hypophosphatemic diseases (i.e., rickets/osteomalacia), while reduced FGF23 activity are linked to hyperphosphatemic diseases (i.e., tumoral calcinosis). Unlike most of the FGF family members, FGF23 needs klotho, as a co-factor to activate its receptor system. In vivo studies have convincingly demonstrated that, in absence of klotho, FGF23 is unable to influence systemic phosphate metabolism. Available information suggests that interactions of FGF23, klotho, and FGFRs regulate renal phosphate metabolism by suppressing sodium-phosphate transporters in the proximal tubular epithelial cells. This article briefly summarizes how bone-kidney communication contributes to physiologic phosphate balance.

Several factors contribute to renal-function decline in CKD patients, and the role of phosphate content in the diet is still a matter of debate. This study aims to analyze the mechanism by which phosphate, independent of protein, is associated with the progression of CKD. Adult Munich-Wistar rats were submitted to 5/6 nephrectomy (Nx), fed with a low-protein diet, and divided into two groups. Only phosphate content (low phosphate, LoP, 0.2%; high phosphate, HiP, 0.95%) differentiated diets. After sixty days, biochemical parameters and kidney histology were analyzed. The HiP group presented worse renal function, with higher levels of PTH, FGF-23, and fractional excretion of phosphate. In the histological analysis of the kidney tissue, they also showed a higher percentage of interstitial fibrosis, expression of α-actin, PCNA, and renal infiltration by macrophages. The LoP group presented higher expression of beclin-1 in renal tubule cells, a marker of autophagic flux, when compared to...