Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study identifies new risk factor for heart disease among kidney dialysis patients

07.03.2013
Findings show that measurements of carbamylated albumin may help doctors in monitoring dialysis patients; further suggests that amino acid supplementation could offset protein carbamylation

Kidney failure affects 25 million individuals in the U.S. and many more throughout the world. Loss of kidney function means the majority of these patients must undergo dialysis treatments to remove excess fluids and waste products.

Although dialysis therapy coupled with medication has improved the life expectancy for people with kidney failure, for unknown reasons, patients' risk of sudden heart failure and death remains 10 to 20 times greater than average.

Now, a study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) and Massachusetts General Hospital helps explain why this may be the case. Appearing on-line today in Science Translational Medicine, the new findings show that a process known as protein carbamylation contributes to heart disease risk among patients with kidney failure undergoing dialysis, and demonstrates that a blood test to measure carbamylated albumin protein can help clinicians better gauge the effectiveness of dialysis and identify patients at risk of cardiac complications. The findings additionally suggest the need for further investigation to determine if therapy with supplemental amino acids could help to prevent the carbamylation process.

"Patients with kidney failure often accumulate urea in their blood because it is a chemical byproduct of metabolism normally eliminated in the urine or removed by dialysis treatments," explains first author Anders Berg, MD, PhD, a clinical chemist in the Department of Pathology at BIDMC and Instructor in Pathology at Harvard Medical School. Although urea is generally non-toxic, in some cases it can degrade into cyanate, a toxic chemical that binds to and permanently modifies proteins through a process known as carbamylation.

"These modifications can make proteins inactive, or worse, can make them toxic," says Berg. "For example, when the cholesterol-carrying blood proteins LDL and HDL are carbamylated, instead of heading for tissues where they would normally be metabolized, they become attracted to atherosclerotic plaques which can lead to the development of atherosclerosis or hardening of the arteries."

Knowing that there is growing evidence that urea and protein carbamylation are important contributors to the risk of heart disease and death in patients with kidney failure, Berg and his collaborators hypothesized that measurements of carbamylated albumin – the most abundant protein in the blood --could provide an index of patients' blood urea concentrations and could be used in a blood test to provide clinicians with information on how well dialysis treatments are working to remove body waste products from patients with kidney failure.

As predicted, in two independent clinical experiments, the investigators demonstrated that increased carbamylated albumin is strongly associated with an elevated risk of premature death in patients on dialysis. They additionally found that increased carbamylated albumin in dialysis patients was linked with low blood concentrations of amino acids, the building blocks of proteins.

"This suggests that amino acid deficiencies may contribute to increased protein carbamylation in dialysis patients," says Berg. "In separate experiments in both cells and in mice, we found that amino acids act as carbamylation scavengers, competitively inhibiting protein carbamylation."

The researchers were able to generate their findings through a variety of complex studies, including protein screening experiments to search for sites of carbamylation on albumin and observational studies in which they first measured albumin carbamylation in blood samples from patients with kidney disease and then followed the patients to determine whether the extent of carbamylation correlated with risk of premature death. The investigators also measured blood concentrations of amino acids in 187 patients to determine if amino acid deficiencies were linked with increased protein carbamylation. They also conducted experiments to test whether inducing amino acid deficiencies in animals led to increased protein carbamylation by urea. Finally, they conducted test tube experiments to investigate whether amino acids could directly inhibit protein carbamylation.

"Although dialysis therapy is life-saving and necessary to remove excess water and urea for patients with kidney failure, it also depletes patients' amino acids and other essential nutrients. In this way it removes both the good and the bad, and thus simply increasing patients' dialysis treatments will not necessarily reduce protein carbamylation," says Berg, adding that future studies will be needed to test whether amino-acid supplementation therapy reduces protein carbamylation and its associated risks, or if there are ways of modifying dialysis methods in order to remove urea without depleting amino acids.

"The mechanisms that lead to cardiovascular disease in patients with chronic kidney disease have remained elusive," says nephrologist Vikas Sukhatme, MD, PhD, Chief Academic Officer of BIDMC. "This paper provides an important first step in identifying kidney failure patients on dialysis at risk for cardiovascular disease and providing a rationale for treating them with inexpensive and non-toxic medicines such as amino acids."

Study coauthors include BIDMC investigators Roberto Buccafusca, Tammy Hod, Wenda Ramma, Samir M. Parikh, David J. Friedman, John Danziger, and senior author and Howard Hughes Medical Institute investigator S. Ananth Karumanchi; Christiane Drechsler and Christoph Wanner, of the University of Würzburg, in Germany; Julia Wenger, Sahir Kalim, and Ravi Thadhani of Massachusetts General Hospital; and Hanno Steen of Children's Hospital Boston.

This work was funded, in part, by support from the Howard Hughes Medical Institute, the National Institutes of Health (K24 DK094872) and the University Hospital Wurzberg "Gundausstattung" grant program.

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and currently ranks third in National Institutes of Health funding among independent hospitals nationwide. BIDMC is clinically affiliated with the Joslin Diabetes Center and is a research partner of the Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.

Bonnie Prescott | EurekAlert!
Further information:
http://www.bidmc.harvard.edu
http://www.bidmc.org

More articles from Studies and Analyses:

nachricht Some brain tumors may respond to immunotherapy, new study suggests
11.12.2018 | Columbia University Irving Medical Center

nachricht Climate change and air pollution damaging health and causing millions of premature deaths
30.11.2018 | International Institute for Applied Systems Analysis (IIASA)

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Data use draining your battery? Tiny device to speed up memory while also saving power

The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.

Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Data use draining your battery? Tiny device to speed up memory while also saving power

14.12.2018 | Power and Electrical Engineering

Tangled magnetic fields power cosmic particle accelerators

14.12.2018 | Physics and Astronomy

In search of missing worlds, Hubble finds a fast evaporating exoplanet

14.12.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>