Nav: Home

Faulty sensing: Cellular energy sensor linked to the progression of chronic kidney disease

December 07, 2018

Tokyo, Japan - Chronic kidney disease (CKD), an affliction characterized by progressive loss of kidney function, affects millions of people worldwide and is associated with multi-organ damage, cardiovascular disease, and muscle wasting. Just like engines, living cells require energy to run, thus the combined millions of cells forming an organ have huge energy requirements. Although the heart has the highest energy needs of all human organs, the kidneys come a close second. Energy depletion can result in kidney damage and the build-up of toxic compounds in the body, contributing to the progression of CKD. Currently, there is no effective treatment to halt this progression.

Adenosine triphosphate (ATP) is the major "fuel" in most living cells and is converted to adenosine monophosphate (AMP) during energy transfer. A specialized energy sensor called 5?-AMP-activated protein kinase (AMPK) detects even the slightest changes in cellular energy by sensing AMP levels, triggering the production of ATP in response to energy depletion. However, AMPK activity is decreased in CKD and the mechanism controlling this dysregulation is unclear.

Now, a research team from TMDU and Kyushu University has shown that failure to sense AMP is the key mechanism underlying the inactivity of AMPK in CKD. In a recent study published in Kidney International, they outline how they came to this conclusion and what it may mean for CKD patients.

"Metabolites can tell us a lot about what's going on in a cell," explains lead author Hiroaki Kikuchi. "In CKD mice, metabolite profiling showed that despite high levels of AMP, there was a substantial decrease in AMPK activation, leading us to conclude that the AMP-sensing function of AMPK was defective."

Armed with this new information, the researchers tried bypassing the AMP-sensing mechanism to determine whether AMPK could still be activated in CKD mice. By treating the mice with A-769662, an AMPK activator that binds at a different site to AMP, they could significantly attenuate CKD progression and correct associated tissue damage.

Critically, the build-up of waste products in the blood as a result of reduced kidney function was shown to be responsible for the decreased AMP-sensing activity of AMPK. "Our findings suggest that energy depletion, CKD progression, and the accumulation of toxic metabolites form a vicious cycle in CKD patients," says co-corresponding author Eisei Sohara. "However, AMPK activation via AMP-independent mechanisms can break this cycle and represents a novel therapeutic approach for the treatment of CKD."
-end-
The article, "Failure to sense energy depletion may be a novel therapeutic target in chronic kidney disease", was published in Kidney International at https://doi.org/10.1016/ j.kint.2018.08.030.

Tokyo Medical and Dental University

Related Chronic Kidney Disease Articles:

Combating chronic kidney disease with exercise
A University of Delaware research team is combating chronic kidney disease (CKD) with exercise.
'Goldilocks' drug prevents chronic kidney disease in primates
A Massachusetts General Hospital research team has developed a way to avoid ischemia/reperfusion injury of the kidney with a new monoclonal antibody that binds its target receptor in a way that is 'just right.'
Reflux and ulcer medications linked to kidney stones and chronic kidney disease
Individuals who took proton pump inhibitors or histamine receptor-2 blockers for heartburn, acid reflux, or ulcers had elevated risks of developing kidney stones.
Allopurinol does not increase chronic kidney disease risk in gout patients
Allopurinol, a widely used treatment for lowering serum urate levels, does not appear to increase risk of kidney deterioration in gout patients with normal or near-normal kidney function, according to new research findings presented this week at the 2016 ACR/ARHP Annual Meeting in Washington.
Research connects first-time kidney stone formers and chronic kidney disease
Mayo Clinic nephrologists have uncovered a connection between first-time kidney stone formers and chronic kidney disease.
More Chronic Kidney Disease News and Chronic Kidney Disease Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#534 Bacteria are Coming for Your OJ
What makes breakfast, breakfast? Well, according to every movie and TV show we've ever seen, a big glass of orange juice is basically required. But our morning grapefruit might be in danger. Why? Citrus greening, a bacteria carried by a bug, has infected 90% of the citrus groves in Florida. It's coming for your OJ. We'll talk with University of Maryland plant virologist Anne Simon about ways to stop the citrus killer, and with science writer and journalist Maryn McKenna about why throwing antibiotics at the problem is probably not the solution. Related links: A Review of the Citrus Greening...