Soluble α-klotho as a novel biomarker in the early stage of nephropathy in patients with type 2 diabetes

PLoS One. 2014 Aug 1;9(8):e102984. doi: 10.1371/journal.pone.0102984. eCollection 2014.


Objective: Although α-klotho is known as an anti-aging, antioxidant, and cardio-renal protective protein, the clinical implications of soluble α-klotho levels in patients with diabetes have not been evaluated. Therefore, this study evaluated whether plasma and urinary α-klotho levels are associated with albuminuria in kidney disease in diabetes.

Research design and methods: A total of 147 patients with type 2 diabetes and 25 healthy control subjects were enrolled. The plasma and urine concentrations of α-klotho were analyzed by enzyme-linked immunosorbent assay.

Results: Plasma α-klotho (572.4 pg/mL [95% CI, 541.9-604.6 pg/mL] vs. 476.9 pg/mL [95% CI, 416.9-545.5 pg/mL]) and urinary α-klotho levels (59.8 pg/mg creatinine [95% CI, 43.6-82.0 pg/mg creatinine] vs. 21.0 pg/mg creatinine [95% CI, 9.7-45.6 pg/mg creatinine]) were significantly higher in diabetic patients than non-diabetic controls. Among diabetic patients, plasma α-klotho concentration was inversely associated with albuminuria stages (normoalbuminuria, 612.6 pg/mL [95% CI, 568.9-659.6 pg/mL], microalbuminuria, 551.8 pg/mL [95% CI, 500.5-608.3 pg/mL], and macroalbuminuria, 505.7 pg/mL [95% CI, 439.7-581.7 pg/mL] (p for trend = 0.0081), while urinary α-klotho levels were remained constantly high with increasing urinary albumin excretion.

Conclusions: Soluble α-klotho levels in plasma and urine may be novel and useful early markers of diabetic renal injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Albuminuria
  • Biomarkers / blood
  • Biomarkers / urine
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / urine
  • Diabetic Nephropathies / blood*
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / urine
  • Female
  • Glucuronidase / blood*
  • Glucuronidase / urine
  • Humans
  • Klotho Proteins
  • Male
  • Middle Aged
  • Risk Factors


  • Biomarkers
  • Glucuronidase
  • Klotho Proteins

Grant support

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2012R1A1A2044121) and the Soonchunhyang University Research Fund (No. 20130626). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.