Cause of heart disease spurred by kidney syndrome found, neutralized

February 28, 2014 by Elizabethe Holland Durando
Cause of heart disease spurred by kidney syndrome found, neutralized
Senior author Keith A. Hruska with other School of Medicine scientists involved in the research. From left, Michael Seifert, MD, Olga Agapova, PhD, Hruska, Toshifumi Sugatani, PhD, DDS, and first author Yifu Fang, MD. Credit: Robert Boston

Chronic kidney disease affects 26 million Americans, but its sufferers are more likely to die of heart disease than kidney problems. However, it hasn't been clear just how kidney disease causes heart disease or what could be done to stop it.

But a new study in mice and people by researchers at Washington University School of Medicine in St. Louis has pinpointed the cause of a kidney-related syndrome also linked to heart disease. Further, they have discovered how to neutralize a protein produced by the kidney that spurs heart disease, illuminating a new approach to tackling health problems brought on by kidney disease.

The findings one day could improve the health and survival rates of those suffering from -mineral bone disorder (CKD-MBD), according to the study's senior author, Keith A. Hruska, MD, a kidney specialist at the School of Medicine.

"We've shown that kidney disease causes diseases of the and heart—and has targets that could be used therapeutically to treat associated heart problems," Hruska said. "And this discovery, serendipitously, shows that antibody-based drugs currently in clinical development potentially could be used to reduce deaths from related heart disease, as well as skeletal and other afflictions caused by CKD-MBD."

The research is available online Feb. 27 in the Journal of the American Society of Nephrology.

CKD-MBD is a common problem in people with kidney disease. In addition to weakening the bones, CKD-MBD shifts hormone levels in the blood, increasing the risk of heart disease.

To understand the link between kidney disease and heart disease, the researchers set out to see and study CKD-MBD at its inception, early in the course of kidney disease. What they found, in mouse models of diabetes with kidney disease, was that with even a very mild kidney injury CKD-MBD would be initiated.

This would happen because as soon as the kidney detected disease or an injury to itself, it would attempt to repair it, behaving much as it does during embryonic development. But in doing so, it would produce and circulate proteins that would harm other parts of the body, including the heart, essentially causing far more harm than good.

For example, the researchers found that kidney injury would spur a surge of the kidney protein Dkk1 in the circulation. Left unchecked, the protein can cause the hardening, or calcifying, of blood vessels, eventually leading to heart disease. But when the scientists neutralized the protein with an antibody, they were surprised to find that problems with blood vessels, including vascular calcification, were prevented.

"Neutralizing Dkk1 with an antibody actually corrects the skeletal and vascular disorders associated with kidney disease," said Hruska, a professor of pediatrics, of medicine and of cell biology and physiology.

The researchers also analyzed levels of Dkk1 in 38 patients with mild kidney disease, finding elevated levels of not only Dkk1 and other related proteins but also of the hormone FGF23, an indicator of heart disease onset. This follows the same pattern as seen in the mouse models, supporting the notion that findings in the laboratory could be applied clinically.

When the authors of the study combined the antibody against Dkk1 with phosphate binders—medications that reduce the absorption of harmful phosphates into a patient's blood—they were able to prevent the increase in FGF23 along with preventing vascular disease.

An antibody to Dkk1 currently is being used in clinical trials for multiple myeloma. Hruska wants to see it developed as a therapeutic to treat the heart and skeletal problems associated with CKD-MBD. And there are other antibodies with similar potential to fight kidney disease, he said.

"The fundamental issue here is that kidney disease directly causes cardiovascular disease through this attempt at trying to repair the injured, diseased kidney," Hruska explained. "And we are hopeful that neutralization of these factors may become a viable therapy for associated with . This could be a significant paradigm shift forward."

Explore further: Kidney patients may gain from less salt

More information: Fang Y, Ginsberg C, Seifert M, Agapova O, Sugatani T, Register TC, Freedman BI, Monier-Faugere M, Malluche H, Hruska KA. "CKD-Induced Wingless/Integration1 Inhibitors and Phosphorus Cause the CKD-Mineral and Bone Disorder. "Journal of the American Society of Nephrology. Online Feb. 27, 2014.

Related Stories

Kidney patients may gain from less salt

January 31, 2014
(Medical Xpress)—Reducing salt consumption may help prolong the lives of patients with chronic kidney disease, a study from The University of Queensland study has found

Physical activity may slow kidney function decline in patients with kidney disease

December 12, 2013
Increased physical activity may slow kidney function decline in patients with kidney disease, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The findings suggest ...

LDL cholesterol is a poor marker of heart health in patients with kidney disease

May 16, 2013
LDL cholesterol is not a useful marker of heart disease risk in patients with kidney disease, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The finding suggests ...

Many kidney disease patients experience hazardous events related to their medical care

February 20, 2014
In addition to experiencing negative health effects from their disease, patients with chronic kidney disease (CKD) are also at risk of experiencing hazardous events potentially related to medical treatments they receive. ...

Consuming more vegetable protein may help kidney disease patients live longer

November 7, 2013
Increased consumption of vegetable protein was linked with prolonged survival among kidney disease patients in a new a study. The findings will be presented at ASN Kidney Week 2013 November 5-10 at the Georgia World Congress ...

Kidney disease coupled with heart disease common problem in elderly

April 21, 2011
Chronic kidney disease (CKD) is common and linked with heart disease in the very elderly, according to a study appearing in an upcoming issue of the Clinical Journal of the American Society Nephrology (CJASN).

Recommended for you

Google searches can be used to track dengue in underdeveloped countries

July 20, 2017
An analytical tool that combines Google search data with government-provided clinical data can quickly and accurately track dengue fever in less-developed countries, according to new research published in PLOS Computational ...

MRSA emerged years before methicillin was even discovered

July 19, 2017
Methicillin resistant Staphylococcus aureus (MRSA) emerged long before the introduction of the antibiotic methicillin into clinical practice, according to a study published in the open access journal Genome Biology. It was ...

New test distinguishes Zika from similar viral infections

July 18, 2017
A new test is the best-to-date in differentiating Zika virus infections from infections caused by similar viruses. The antibody-based assay, developed by researchers at UC Berkeley and Humabs BioMed, a private biotechnology ...

'Superbugs' study reveals complex picture of E. coli bloodstream infections

July 18, 2017
The first large-scale genetic study of Escherichia coli (E. coli) cultured from patients with bloodstream infections in England showed that drug resistant 'superbugs' are not always out-competing other strains. Research by ...

Ebola virus can persist in monkeys that survived disease, even after symptoms disappear

July 17, 2017
Ebola virus infection can be detected in rhesus monkeys that survive the disease and no longer show symptoms, according to research published by Army scientists in today's online edition of the journal Nature Microbiology. ...

Mountain gorillas have herpes virus similar to that found in humans

July 13, 2017
Scientists from the University of California, Davis, have detected a herpes virus in wild mountain gorillas that is very similar to the Epstein-Barr virus in humans, according to a study published today in the journal Scientific ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.