Serum and Urinary Soluble α-Klotho as Markers of Kidney and Vascular Impairment

Julia Martín-Vírgala1,2, Sara Fernández-Villabrille1,2, Beatriz Martín-Carro1,2

  • 1Bone and Mineral Research Unit, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias (HUCA), Universidad de Oviedo, 33011 Oviedo, Spain.

Nutrients
|March 29, 2023
PubMed

Insights

Soluble Klotho (sKlotho) emerges as the earliest biomarker for Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD), reliably indicating kidney health and potentially preventing vascular calcification by enhancing autophagy.

Area of Science:

  • Nephrology
  • Endocrinology
  • Cell Biology

Background:

  • Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) is a complex condition with unclear early diagnostic markers.
  • The role of soluble Klotho (sKlotho) as a biomarker and its impact on vascular health in CKD-MBD require further elucidation.

Purpose of the Study:

  • To investigate sKlotho as an early biomarker for CKD-MBD.
  • To determine if sKlotho reliably reflects kidney α-Klotho levels.
  • To explore sKlotho's effects on vascular smooth muscle cell (VSMC) osteogenic differentiation and the role of autophagy.

Main Methods:

  • Experimental studies in Chronic Kidney Disease (CKD) mice on normal or high phosphorus diets.
  • Analysis of patient data from CKD stages 2-5.
  • In vitro studies using VSMCs treated with or without sKlotho in calcifying conditions.

Main Results:

  • CKD mice on high phosphorus diets exhibited elevated PTH, P, FGF23, and reduced sKlotho.
  • Serum sKlotho levels positively correlated with kidney α-Klotho.
  • sKlotho decline preceded FGF23 increase in human CKD patients, correlating with kidney function.
  • In vitro, sKlotho prevented VSMC osteogenic differentiation and induced autophagy.

Conclusions:

  • Serum sKlotho is the earliest CKD-MBD biomarker and a reliable indicator of kidney α-Klotho.
  • sKlotho may protect against vascular osteogenic differentiation by promoting autophagy.
  • Further research is needed to fully understand the protective mechanisms of sKlotho.

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