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Soluble Klotho, a Potential Biomarker of Chronic Kidney Disease-Mineral Bone Disorders Involved in Healthy Ageing:
Julia Martín-Vírgala1,2, Beatriz Martín-Carro1,2, Sara Fernández-Villabrille1,2
1Metabolismo Óseo, Vascular y Enfermedades Inflamatorias Crónicas, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain.
Insights
Soluble Klotho (sKlotho) levels decrease in chronic kidney disease (CKD), potentially linking to CKD-mineral bone disorders. However, inconsistent findings highlight the need for standardized assays and further research into sKlotho
Area of Science:
- Biochemistry
- Nephrology
- Gerontology
Background:
- Klotho protein, particularly the αKlotho isoform, is increasingly studied for its role in chronic kidney disease (CKD).
- Soluble Klotho (sKlotho) is released from kidneys into circulation and urine, exerting systemic effects, often with FGF23.
- Reduced sKlotho levels are observed early in CKD and are hypothesized to correlate with CKD-mineral bone disorders (CKD-MBDs).
Purpose of the Study:
- To review the potential of αKlotho, specifically sKlotho, as a biomarker in CKD and CKD-MBD.
- To identify inconsistencies in current research and highlight areas needing further investigation.
- To explore the relationship between sKlotho, healthy aging factors (exercise, social interaction, caloric restriction), and CKD.
Main Methods:
- Literature review focusing on studies investigating αKlotho and sKlotho in the context of CKD and CKD-MBD.
- Analysis of factors influencing sKlotho levels, including aging and lifestyle.
- Examination of methodological challenges affecting sKlotho research.
Main Results:
- sKlotho is recognized for its systemic actions and potential as a biomarker in CKD.
- Inconsistencies in sKlotho's role as a CKD-MBD biomarker are attributed to small sample sizes, study quality, assay standardization, and sample processing issues.
- Exercise and social interaction correlate with higher sKlotho levels, while the effect of caloric restriction remains unclear.
Conclusions:
- The utility of sKlotho as a reliable biomarker for CKD-MBD remains controversial due to significant research inconsistencies.
- Standardization of assays and rigorous study designs are crucial for clarifying sKlotho's biomarker potential.
- Further research is needed to fully understand sKlotho's role in aging and its implications for kidney disease and bone health.
Abstract:
Shortly after the discovery of Klotho, interest grew in its potential role in chronic kidney disease (CKD). There are three isoforms of the Klotho protein: αKlotho, βKlotho and γKlotho. This review will focus on αKlotho due to its relevance as a biomarker in CKD. αKlotho is synthesized mainly in the kidneys, but it can be released into the bloodstream and urine as soluble Klotho (sKlotho), which undertakes systemic actions, independently or in combination with FGF23. It is usually accepted that sKlotho levels are reduced early in CKD and that lower levels of sKlotho might be associated with the main chronic kidney disease-mineral bone disorders (CKD-MBDs): cardiovascular and bone disease. However, as results are inconsistent, the applicability of sKlotho as a CKD-MBD biomarker is still a matter of controversy. Much of the inconsistency can be explained due to low sample numbers, the low quality of clinical studies, the lack of standardized assays to assess sKlotho and a lack of consensus on sample processing, especially in urine. In recent decades, because of our longer life expectancies, the prevalence of accelerated-ageing diseases, such as CKD, has increased. Exercise, social interaction and caloric restriction are considered key factors for healthy ageing. While exercise and social interaction seem to be related to higher serum sKlotho levels, it is not clear whether serum sKlotho might be influenced by caloric restriction. This review focuses on the possible role of sKlotho as a biomarker in CKD-MBD, highlighting the difference between solid knowledge and areas requiring further research, including the role of sKlotho in healthy ageing.
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