FGF23 is the key regulator of phosphate metabolism, and high FGF23 levels are associated with increased cardiovascular risk . The α-Klotho protein is a co-receptor specific for FGF23 [10–12]. α-Klotho was first identified as an aging gene  and was later shown to be a regulator of phosphate metabolism. α-Klotho exists in 2 forms, namely a membrane form and a circulation (secreted soluble) form.
Membrane α-Klotho forms a co-receptor for FGF23, especially in the distal tubules of the kidney [14, 15]. Secreted α-Klotho arises from shedding of membrane α-Klotho in the kidney by membrane-anchored proteases [16, 17]. Secreted α-Klotho is found in the cerebrospinal fluid, blood, and urine [14, 18] and has various functions. α-Klotho deficiency leads to ectopic soft tissue calcification.
On the other hand, overexpression of α-Klotho selleck chemical reduces ectopic calcification in α-Klotho-deficient phenotypes. A CP673451 in vivo previous report suggested that α-Klotho may be an inhibitor of ectopic calcification . Recently, secreted α-Klotho has been reported to function as a regulator AZD5582 nmr of phosphate metabolism, independently of FGF23 [19–21]. Secreted α-Klotho increases calcium (Ca) reabsorption and potassium excretion in the distal tubule via N-linked glycans of TRPV5 and ROMK1 [19–21]. Further, α-Klotho decreases phosphate reabsorption in the proximal tubule via N-linked glycans of NaPi-2a . α-Klotho level is influenced by creatinine, Ca, and phosphate concentration and age in the healthy population, with a negative association reported for age . Previous studies have suggested that α-Klotho plays a physiological and pathophysiological role in CKD. However, serum levels of secreted soluble α-Klotho in CKD patients have not previously been determined, especially in relation with FGF23, creatinine, and phosphate
levels. This study was designed to investigate whether serum soluble α-Klotho level is modulated by renal function, age, and FGF23 concentration, and to examine the potential role of soluble α-Klotho in mineral and bone disorder (MBD) in CKD patients. The aim of this study was to determine the utility of serum soluble α-Klotho as a new biomarker LY294002 for the diagnosis of CKD, especially in the early stage. Materials and methods All patients who provided informed consent for participation in the project were enrolled in the study. The study protocol was approved by the institutional review board of Kochi Medical School and Kochi Takasu Hospital. Enrolment took place from November 2010 to October 2011 at Kochi Medical School Hospital and Kochi Takasu Hospital. A total of 292 patients with CKD were enrolled. All subjects had >1 outpatient determination of serum creatinine level, and none had previously received renal replacement therapy. Patients were followed-up from the time of the first serum creatinine measurement. We used the new Japanese equation for the estimation of glomerular filtration rate (GFR) [estimated GFR (eGFR) in mL/min per 1.