**1. Introduction**

Chronic kidney disease (CKD) causes alterations in mineral metabolism, which worsens as the renal disease progresses. It is observed that with only a marginal decrease of glomerular filtration, there is a downregulation of renal α-Klotho (Klotho) [1]. Renal Klotho is the co-receptor of Fibroblast Growth Factor Receptor-1 (FGFR1), the specific receptor of the phosphaturic hormone Fibroblast Growth Factor-23 (FGF23). Thus, FGF23 promotes urinary excretion of phosphate and prevents hyperphosphatemia until the glomerular filtration rate falls below 15–20 mL/min. In addition to α-Klotho, expressed in tubular cell membranes, there are two other types of Klotho: soluble (sKlotho) and secreted Klotho, with additional effects in other organs. Actually, there are studies showing the pleiotropic effects of Klotho in the cardiovascular system [2], bone [3], and even as a tumor suppressor molecule [4,5]. The mechanisms behind this reduction of renal α-Klotho during CKD are unclear, and they are attributed mainly to kidney function deterioration, although Wnt/β-catenin activation has also been suggested as a key factor leading to Klotho reduction [6].

FGF23 is a hormone produced mainly in mature osteoblasts and osteocytes, and in addition to its phosphaturic effect, it also inhibits 1,25(OH)2D and PTH production [7]. In CKD patients, the concentration of plasma FGF23 increases progressively in part due to kidney resistance to the action of FGF23 generated by the lack of the co-receptor α-Klotho. An experiment in animals demonstrated that the reduction of α-Klotho is precipitated by an excessive tubular load of phosphate [6,8]. In fact, the increase in FGF23 levels is accompanied by a marked decrease in Klotho. Drueke et al. showed a descriptive illustration where it is collected through progressive changes in the parameters of mineral metabolism, and through CKD parameters during renal disease progression [1]. It is interesting to note that in parallel to the decrease of Klotho, and the increase of FGF23, there are also changes in the levels of Wnt inhibitors, such as sclerostin or Dickkopf-related proteins (Dkk1). However, the relationship between the FGF23/Klotho axis and Wnt signaling has not been sufficiently explored.

Works from different researchers have described an interrelationship between alterations in mineral metabolism and changes in Wnt signaling in the kidney, vessels, heart, bone, and brain, among others. This review will summarize the relationship between Wnt signaling, FGF23, and Klotho expression.
