The relationship between α-Klotho and FGF23 levels has previously been examined in experimental animal studies [30]. In α-Klotho-deficient mice, FGF23 level was significantly elevated; further, infusion of FGF23 repressed the expression of α-Klotho in a mouse model [13]. However, no data have been reported on the relationship between soluble

α-Klotho and FGF23 concentration in humans. We have demonstrated clearly that soluble α-Klotho is negatively correlated with FGF23 level in CKD patients. We have also shown that soluble α-Klotho level is decreased in the second phase of CKD. Soluble α-Klotho in itself moderates urinary phosphate excretion by inhibiting renal NaPi-2a and NaPi-2c in renal proximal tubules [31]. A see more decrease in soluble α-Klotho level thus causes elevation of serum phosphate levels, which may stimulate the production of FGF23. Our clinical data are therefore in accordance with the learn more findings from previous animal studies. Our data indicate that α-Klotho and FGF23 may play a key role in the pathogenesis

of mineral and bone disorder in the relatively early phase of CKD. A limitation of our study is that we did not investigate α-Klotho levels in normal healthy volunteers for comparison. Yamazaki et al. [22] reported that secreted α-Klotho level was associated with age in the healthy population. Our data indicate that secreted soluble α-Klotho level also was influenced by age in a population of CKD patients. Therefore, we must consider age during the assessment of secreted soluble α-Klotho levels, if soluble α-Klotho is to be used as a biomarker for CKD. PI-1840 Stage 1 CKD patients were younger than those with stage 2 in LY3023414 in vitro our study. The reason for this discrepancy is simply the inclusion of a relatively small number

of elderly patients with proteinuria and an eGFR of >90 mL/min. We performed additional stepwise multiple regression analysis to examine whether age affects the level of soluble secreted α-Klotho in patients with CKD stage 1 or 2. As shown in Table 2, eGFR, but not age, was the most potent influencer of soluble secreted α-Klotho level. Further studies using both healthy volunteers and CKD patients are necessary to evaluate the physiological and pathophysiological mechanisms of serum secreted α-Klotho. In summary, our data indicate that soluble secreted α-Klotho may represent a new predictive marker for the progression of CKD, especially in the early stages of the disease. Further studies are necessary to gain a more precise understanding of the function of α-Klotho in CKD and its role in the pathogenesis of MBD. Acknowledgments This work was supported by Daiwa Memorial foundation, Japanese Kidney foundation, and a grant from the Ministry of Education, Science, Culture and Sports of Japan (to Y. S., K. I., K. O., S. F., and Y. T.) and a grant of Kochi Organization for Medical Reformation and Renewal to Y.T. We thank Ms. Reiko Matumoto, Ms. Sekie Saito for technical assistances. References 1.