αKlotho and Chronic Kidney Disease.

Area of Science:

• Biochemistry
• Nephrology
• Endocrinology

Background:

• Alpha-Klotho (αKlotho) is a coreceptor for FGF23, crucial for mineral metabolism.
• Soluble αKlotho levels decrease early in chronic kidney disease (CKD), indicating kidney function decline.
• αKlotho deficiency is linked to CKD progression and extrarenal complications.

Purpose of the Study:

• To investigate the role of αKlotho in CKD pathogenesis and its potential as a therapeutic target.
• To evaluate the impact of αKlotho decline on renal and extrarenal complications.
• To explore strategies for preventing αKlotho decline or supplementing its levels.

Main Methods:

• Analysis of soluble and urinary αKlotho levels in relation to CKD stages.
• Review of preclinical data from animal models of αKlotho deficiency.
• Assessment of interventions aimed at modulating αKlotho levels in CKD models.

Main Results:

• Soluble αKlotho declines early in CKD (stage 2), with urinary αKlotho decreasing even earlier (stage 1).
• αKlotho deficiency promotes CKD progression, cell senescence, apoptosis, impaired autophagy, and fibrosis.
• Preventing αKlotho decline or supplementing it attenuates renal fibrosis, slows CKD progression, and improves mineral metabolism, cardiac, and vascular health.

Conclusions:

• Soluble αKlotho is a sensitive early biomarker for kidney function decline in CKD.
• αKlotho deficiency is a key pathogenic factor in CKD and its complications.
• Enhancing endogenous αKlotho or administering exogenous αKlotho are promising therapeutic strategies for CKD.