(Press-News.org) DALLAS – Feb. 17, 2011 – Low levels of the anti-aging hormone Klotho may serve as an early warning sign of the presence of kidney disease and its deadly cardiovascular complications, according to findings by UT Southwestern Medical Center researchers.
Using mice, investigators found that soft-tissue calcification, a common and serious side effect of chronic kidney disease (CKD), improves when Klotho hormone levels are restored. The study is available online in the Journal of the American Society of Nephrology.
The essential Klotho protein, which is produced by the kidneys, often plummets in CKD. 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 said. 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 said. "Chronic kidney disease appears to go hand-in-hand with chronic Klotho deficiency. Animal studies have shown that a dangerous consequence of inadequate Klotho is soft-tissue calcification, which can interfere with normal organ function."
In the current study, UT Southwestern researchers decreased Klotho levels in mice by genetically engineering them to produce inadequate levels of the protein. Restoring adequate Klotho levels to the rodents with CKD markedly improved renal function and blood chemistry and reduced vascular calcification.
In contrast, mice with CKD that were genetically engineered to have abnormally low levels of Klotho had worse kidney function and severe calcification. 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 said.
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 said. "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 said.
###
Other UT Southwestern researchers involved in the study were Dr. Ming-Chang Hu, instructor of internal medicine and lead author; Dr. Makoto Kuro-o, associate professor of pathology who discovered Klotho more than a decade ago; Mingjun Shi, research associate in internal medicine; Dr. Jianning Zhang, research scientist in internal medicine; Dr. Henry Quinones, assistant professor of internal medicine; and Carolyn Griffith, senior research nurse in mineral metabolism.
Primary funding for the study was provided by the Simmons Family Foundation. Other support was given by the National Institutes of Health, the George M. O'Brien Kidney Research Core Center at UT Southwestern, the American Heart Association, the Eisai Research Fund, Ellison Medical Foundation, Ted Nash Long Life Foundation, and the Charles & Jane Pak Center for Mineral Metabolism and Clinical Research.
Visit www.utsouthwestern.org/kidneys to learn more about UT Southwestern's clinical services for kidneys.
This news release is available on our World Wide Web home page at
http://www.utsouthwestern.edu/home/news/index.html
To automatically receive news releases from UT Southwestern via e-mail,
subscribe at www.utsouthwestern.edu/receivenews
Anti-aging hormone Klotho may prevent complications
2011-02-20
ELSE PRESS RELEASES FROM THIS DATE:
How disordered proteins spread from cell to cell, potentially spreading disease
2011-02-20
One bad apple is all it takes to spoil the barrel. And one misfolded protein may be all that's necessary to corrupt other proteins, forming large aggregations linked to several incurable neurodegenerative diseases such as Huntington's, Parkinson's and Alzheimer's.
Stanford biology Professor Ron Kopito has shown that the mutant, misfolded protein responsible for Huntington's disease can move from cell to cell, recruiting normal proteins and forming aggregations in each cell it visits.
Knowing that this protein spends part of its time outside cells "opens up the possibility ...
A better way to diagnose pneumonia
2011-02-20
Researchers from the Georgia Institute of Technology have created a new sampling device that could prevent thousands of people worldwide from dying of pneumonia each year.
Called PneumoniaCheck, the device created at Georgia Tech is a solution to the problem of diagnosing pneumonia, which is a major initiative of the U.S. Centers for Disease Control and Prevention (CDC).
Pneumonia, an inflammation of the lungs, kills about 2.4 million people each year. The problem is particularly devastating in Africa, Southeast Asia and the Eastern Mediterranean, where a child dies ...
New model for probing antidepressant actions
2011-02-20
The most widely prescribed antidepressants – medicines such as Prozac, Lexapro and Paxil – work by blocking the serotonin transporter, a brain protein that normally clears away the mood-regulating chemical serotonin. Or so the current thinking goes.
That theory about how selective serotonin reuptake inhibitors (SSRIs) work can now be put to the test with a new mouse model developed by neuroscientists at Vanderbilt University.
These mice, described in the online edition of the Proceedings of the National Academy of Sciences (PNAS), express a serotonin transporter that ...
Enhancing nuclear security: Training and international collaboration
2011-02-20
While a world free of nuclear weapons remains a goal for governments around the world, nuclear security constitutes a major challenge for the 21st century, as recognised at the 2010 nuclear security summit in Washington. Citizens are generally aware of international efforts to prevent the proliferation of nuclear weapons, but they are often unaware of nuclear security research and the important role science in this field. A new European nuclear security training centre and enhanced international collaboration are good examples.
A recent survey on the EU´s radiological ...
Turning to nature for inspiration
2011-02-20
To build the next generation of sensors – with applications ranging from medical devices to robotics to new consumer goods – Chang Liu looks to biology.
Liu, professor of mechanical engineering and electrical engineering and computer science at Northwestern University's McCormick School of Engineering and Applied Science, is using insights from nature as inspiration for both touch and flow sensors — areas that currently lack good sensors for recording and communicating the senses.
Liu will discuss his research in a symposium at the annual meeting of the American Association ...
Plant breeding is being transformed by advances in genomics and computing
2011-02-20
The arrival of affordable, high throughput DNA sequencing, coupled with improved bioinformatics and statistical analyses is bringing about major advances in the field of molecular plant breeding. Multidisciplinary breeding programs on the world's major crop plants are able to investigate genome-wide variations in DNA sequences and link them to the inheritance of highly complex traits controlled by many genes, such as hybrid vigor. Furthermore, there has been a step-change in speed and cost-effectiveness. What previously took six generations to achieve can now be done in ...
AAAS Symposium: New research facilitates scientific knowledge transfer
2011-02-20
NEW YORK, February 4, 2011 –– A defining feature of a scientific discovery is replication by others. In today's age of computational science, this means higher standards of communication of discoveries — making available the data that generated the results along with the published research paper. Doing this makes the technology behind the finding widely accessible, facilitating re-use and verification of results.
Tools and approaches to facilitate such knowledge transfer will be discussed at a symposium titled The Digitization of Science: Reproducibility and Interdisciplinary ...
Weight loss improves knee pain from common arthritic condition, study says
2011-02-20
SAN DIEGO, CA – Knee pain related to osteoarthritis (OA) is a common complaint among obese individuals and retired professional athletes, especially former NFL players, but researchers presenting their work at the American Orthopaedic Society for Sports Medicine's Specialty Day program (February 19th) say they have a simple solution: lose weight.
"Our research on patients who were obese with early-onset knee osteoarthritis showed that those individuals who underwent isolated weight loss via bariatric surgery and lost an average of 57 pounds within the first six months ...
Misguided public perception on what Tommy John surgery can do apparent in new study
2011-02-20
SAN DIEGO, CA – Despite known risks and outcomes of the common elbow procedure known as Tommy John surgery, parents, coaches and players still have incorrect assumptions regarding player performance, say researchers presenting their study at the American Orthopaedic Society for Sports Medicine's Specialty Day in San Diego, CA (February 19th).
"Despite the recognized risk of pitch type and amount of pitches, nearly a third of those we surveyed did not believe pitch counts were a risk factor for injury. Even more disturbing was that fact that a quarter of players and coaches ...
Hamstring grafts prove more effective in ACL knee reconstruction, study says
2011-02-20
SAN DIEGO, CA - Patients receiving anterior cruciate ligament (ACL) knee reconstruction with a hamstring tendon graft rather than a knee tendon graft were less likely to suffer from pain and mobility issues15 years after surgery, say researchers presenting a study today at the American Orthopaedic Society for Sports Medicine's Specialty Day in San Diego, California (February 19).
"While we have seen excellent results in terms of knee symptoms and function with both graft types, comparing the two definitely showed differences, "said Leo Pinczewski, MD, lead researcher ...