An Association Between Klotho Deficiency and Kidney Function

STRONG links have been discovered between the soluble protein Klotho and the decline in kidney function. The Klotho protein, whose gene is named after the Greek goddess believed to be responsible for birth and death, has two types: a secreted ‘soluble Klotho’ which circulates around the blood and a membrane-bound variant. As soluble Klotho is largely expressed in the kidneys, individuals that have kidney disease often display lower levels than normal. The insufficient research currently available on the link between kidney disease and Klotho inspired Dr David Drew, Tufts Medical Center, Boston, Massachusetts, USA, and his team to investigate more into this issue.

Dr Drew and his team enrolled 2,496 participants, from the Health, Aging, and Body Composition Study, with the average age of 75, to undergo a soluble alpha-Klotho assay. The link between kidney function decline and soluble Klotho was evaluated, and researchers monitored the incidences of chronic kidney disease (CKD) over a 10-year follow-up period. The findings were adjusted for comorbidities, demographics, estimated glomerular filtration rate, kidney disease risk factors, and mineral metabolism.

The results suggested that higher levels of soluble Klotho correlated with better kidney function. More specifically, 16% of the 2,496 experienced a 30% decrease in kidney function, yet 28% of participants had an absolute decline >3 mm per minute, per year. A lower risk of decline in kidney function was associated independently with higher levels of soluble Klotho. Researchers also found that there was a 20% lower risk of kidney function decline for each two-fold higher level of soluble Klotho at follow-up.

Although more research needs to be undertaken to replicate their findings in the wider population, the results do appear to indicate that CKD is a condition of soluble Klotho deficiency. Dr Drew explained: “We found a strong association between low soluble Klotho and decline in kidney function, independent of many known risk factors for kidney function decline. This suggests that Klotho could play a role in the development of CKD, although additional research will need to confirm this. This also raises the possibility that Klotho could be an important therapeutic target for future clinical trials.”

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