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Updated: Aug 5, 2025

Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
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.
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.
Abstract:
This study was designed to investigate the controversy on the potential role of sKlotho as an early biomarker in Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD), to assess whether sKlotho is a reliable marker of kidney α-Klotho, to deepen the effects of sKlotho on vascular smooth muscle cells (VSMCs) osteogenic differentiation and to evaluate the role of autophagy in this process. Experimental studies were conducted in CKD mice fed a normal phosphorus (CKD+NP) or high phosphorus (CKD+HP) diet for 14 weeks. The patients' study was performed in CKD stages 2-5 and in vitro studies which used VSMCs exposed to non-calcifying medium or calcifying medium with or without sKlotho. The CKD experimental model showed that the CKD+HP group reached the highest serum PTH, P and FGF23 levels, but the lowest serum and urinary sKlotho levels. In addition, a positive correlation between serum sKlotho and kidney α-Klotho was found. CKD mice showed aortic osteogenic differentiation, together with increased autophagy. The human CKD study showed that the decline in serum sKlotho is previous to the rise in FGF23. In addition, both serum sKlotho and FGF23 levels correlated with kidney function. Finally, in VSMCs, the addition of sKlotho prevented osteogenic differentiation and induced autophagy. It can be concluded that serum sKlotho was the earliest CKD-MBD biomarker, a reliable indicator of kidney α-Klotho and that might protect against osteogenic differentiation by increasing autophagy. Nevertheless, further studies are needed to investigate the mechanisms of this possible protective effect.
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