CKD is probably the most intensively studied area using KLOTHO as biomarker, which is not surprising considering the link to phosphorus homeostasis and vitamin D via its interaction with FGF-23. Clinical data are partly contradictory but most meta analyses (e.g. Liu et al., 2019) showed a positive correlation with eGFR and that KLOTHO serum levels are associated with an increased risk of reaching adverse kidney outcomes in patients with CKD. Overall KLOTHO could be used as a novel indicator for early diagnosis and prognostic assessment of CKD, but prospective studies with larger sample sizes are still required.
The Prognostic Role of Klotho in Patients with Chronic Kidney Disease: A Systematic Review and Meta-analysis. Liu QF et al., Dis Markers. 2019 Jun 2;2019:6468729.
It has been found, that KLOTHO functions as a tumor suppressor predominantly expressed in renal tubular cells, the origin of clear cell renal cell carcinoma (ccRCC). It seems, that this protein is a favorable prognostic factor for ccRCC and exerts tumor suppressive role for ccRCC through inhibiting IGF-1R signaling. However, this finding is based on expression studies in cell culture models and the role of serum KLOTHO levels remains to be established.
Klotho plays a critical role in clear cell renal cell carcinoma progression and clinical outcome.
Kim JH et al., Korean J Physiol Pharmacol. 2016 May;20(3):297-304.
There are a lot of evidences that KLOTHO deficiency correlates with the occurrence and development of coronary artery disease, atherosclerosis, myocardial infarction and left ventricular hypertrophy. This may be a result of the inhibition of insulin/insulin-like growth factor-1 signaling pathway by KLOTHO thus regulating oxidative stress and reducing cell death. These antioxidative and antiapoptotic actions could be considered as a novel protective factor in cardiovascular disease and heart injury. Soluble KLOTHO has been associated with mortality and cardiovascular events, e.g. in hemodialysis patients.
The Biological Role of Klotho Protein in the Development of Cardiovascular Diseases.
Olejnik A et al., Biomed Res Int. 2018 Dec 24;2018:5171945.
KLOTHO deficiency has been linked to aging-like phenotypes such as osteoporosis, cognitive impairment and sarcopenia. Although serum KLOTHO protein levels have been associated with the degree of bone mineral density (BMD) in e.g. hemodialysis patients, no association with fracture risk was found. More prospective studies with larger sample sizes are required to clarify the role of this protein in bone disorders
Klotho, a new marker for osteoporosis and muscle strength in β-thalassemia major. Baldan A et al., Blood Cells Mol Dis. 2015 Dec;55(4):396-401. doi: 10.1016/j.bcmd.2015.08.004. Epub 2015 Aug 24.