Serum levels of soluble secreted α-Klotho are decreased in the early stages of chronic kidney disease, making it a probable novel biomarker for early diagnosis

Clin Exp Nephrol. 2012 Oct;16(5):722-9. doi: 10.1007/s10157-012-0621-7. Epub 2012 Mar 29.


Background: α-Klotho was first identified as an aging gene and was later shown to be a regulator of phosphate metabolism. Fibroblast growth factor 23 (FGF23) is the key regulator of phosphate metabolism. Serum levels of soluble α-Klotho in chronic kidney disease (CKD) patients have not previously been determined, especially in relation with FGF23 and creatinine levels. This study was designed to investigate whether serum soluble α-Klotho levels are modulated by renal function, age, and FGF23 level in CKD patients. This study is the first report on the utility of measuring soluble α-Klotho levels in human CKD.

Methods: A total of 292 CKD patients were enrolled. Serum samples were collected, and FGF23 and soluble α-Klotho levels were measured using enzyme-linked immunosorbent assay kits. In addition, serum creatinine, hemoglobin, albumin, calcium, and phosphate levels were measured.

Results: Serum soluble α-Klotho levels were associated positively with estimated glomerular filtration rate (eGFR) (P < 0.0001) and inversely with serum creatinine level (P < 0.01). Interestingly, α-Klotho levels were significantly decreased in stage 2 CKD compared with stage 1 (P = 0.0001). Serum FGF23 levels were associated positively with serum creatinine and negatively with eGFR. FGF23 levels were significantly increased in stage 5 compared with stage 1 CKD. Soluble α-Klotho was associated inversely with log-transformed FGF23 level (P < 0.01).

Conclusion: Our data indicate that soluble α-Klotho levels are significantly decreased in stage 2 CKD compared to stage 1, and not only in the advanced stages of the disease. Soluble α-Klotho may thus represent a new biomarker for the diagnosis of CKD, especially in the early stage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Early Diagnosis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibroblast Growth Factors / blood
  • Glomerular Filtration Rate
  • Glucuronidase / blood*
  • Humans
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic / blood*


  • Biomarkers
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • Glucuronidase
  • klotho protein