This may explain why supplementing Klotho levels helps counteract a major side-effect associated with the disease, said Dr. Orson Moe, director of the Charles & Jane Pak Center for Mineral Metabolism and Clinical Research at UT Southwestern and the senior author of the study.
Mice with chronic kidney disease exhibit low levels of Klotho in their kidneys, blood and urine, indicating that CKD is a state of systemic Klotho deficiency, Dr. Moe
In the study, researchers also tested urine from 53 human participants, including 40 CKD patients, and found that they also had low levels of the essential protein.
"It can be a vicious cycle, where CKD begets low Klotho and low Klotho accelerates CKD," Dr. Moe
The beneficial effect of proper Klotho levels on vascular calcification goes beyond the hormone's effect on kidney function, suggesting a direct protective effect of Klotho on the vasculature, Dr. Moe
According to the research, Klotho lessens vascular calcification by enhancing the urine's phosphate excretions (essential for building and repairing bones and teeth, helping nerve function and making muscles contract, but it can be toxic when levels are high); and preserving kidney fluid filtration.
Most importantly, Klotho also appears to inhibit vascular smooth-muscle phosphate uptake and calcification, a complication of CKD that can significantly increase risk of death.
"We tested three hypotheses," Dr. Moe
"The first was that CKD is a state of Klotho deficiency; the second, that Klotho is an early marker of CKD; and the third, that Klotho deficiency contributes to vascular calcification and Klotho replacement ameliorates CKD via multiple mechanisms.
The data we collected seem to bear out all three."
The study's findings also suggest that Klotho replacement therapy may eventually prove to be effective in battling CKD as well as in preventing and reversing its complications.
"It is our hope that this and future research will ultimately lead to better ways to retard the progression of CKD and avoid the dire consequences associated with the disease," Dr. Moe