Protein deficiency may explain kidney disease

Chronic kidney disease affects millions of people in the United States each year. New research points to a circulating protein that may be responsible for the decline in kidney function.

The Greek goddess Klotho was responsible for spinning the thread of life. She would decide when people were born, who should be put to death, and who should be spared.

The gene that was named after her may also hold the key to age and life expansion. The Klotho gene was initially identified as a potential age-suppressing gene in mice that could extend the lifespan when overexpressed.

There are two types of the Klotho protein – a membrane-bound Klotho and a secreted “soluble Klotho,” which circulates through the blood.

The gene has been shown to regulate some metabolic processes via endocrine pathways, and some studies have uncovered a link between mineral metabolism and aging.

Patients with kidney disease tend to have low levels of soluble Klotho, since the protein is primarily expressed in the kidney.

Chronic kidney disease (CKD) is a condition in which the kidneys cannot filter blood properly. The illness affects more than 20 million U.S. individuals – or 10 percent of the country’s population.

A team of researchers, led by Dr. David Drew from Tufts Medical Center, set out to examine the link between levels of soluble Klotho and kidney function.

Dr. Drew and team were motivated by the insufficient research available on the association between levels of soluble Klotho and changes in kidney function.

Their findings were published in the Journal of the American Society of Nephrology.

Researchers performed a soluble alpha-Klotho assay in 2,496 participants, who were 75 years old on average, from the Health, Aging, and Body Composition study.

The scientists evaluated the link between soluble Klotho and kidney function decline, as well as the incidence of CKD over a 10-year follow-up period.

Findings were adjusted for demographics, comorbidities, estimated glomerular filtration rate, kidney disease risk factors, and mineral metabolism.

The researchers found a strong link between soluble Klotho and kidney function decline.

Of the 2,496 participants, 16 percent experienced a 30 percent decrease in kidney function, whereas 28 percent had an absolute decline greater than 3 milliliters per minute per year.

Overall, higher levels of soluble Klotho associated independently with a lower risk of decline in kidney function.

Specifically, for each two-fold higher level of soluble Klotho, the scientists found a 20 percent lower risk of kidney function decline at follow-up. These results remained unchanged after adjustment for all the variables, including demographics, CKD risk factors, and mineral metabolism.

The findings seem to suggest, the authors note, that CKD is a condition of soluble Klotho deficiency.

However, the authors advise that future studies should seek to replicate their findings in other populations, and try to uncover the underlying mechanism.