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Discovery could help kidney failure treatment

Tuesday June 16th 2020

Stopping a cell signalling pathway in the kidney could be the key to treating chronic kidney disease as well as other deadly conditions, including heart attack and stroke, according to a new international study.

Research led by the University of Bristol, UK, published in Proceedings of the National Academy of Sciences identified Neuropeptide Y (Npy), which is present in high levels in the brain and helps to maintain body balance, in the filtering unit of the kidney.

The study team found Npy in podocytes, which were sending harmful signals and damaging the glomerulus, leading to proteinuria that can lead to kidney failure if left untreated and is also associated with an increased risk of heart attack or stroke.

Professor Richard Coward, professor of renal medicine at the University of Bristol, said: “Chronic kidney disease affects more than one in 10 of the world’s population, claiming millions of lives every year.

"That makes the discovery of Npy’s detrimental potential in the kidney and ways to block it an exciting step forward, which could play a vital role in developing new treatments for proteinuric kidney disease and its associated complications.”

The collaborative study focused initially on diabetic kidney disease and the team discovered Npy production was massively reduced in diabetic podocyte cells studied in laboratory dishes and Npy levels were also significantly lower in the glomeruli of diabetes patients.

To understand the importance of Npy in the kidney, they studied mice that were both able and unable to produce Npy, finding that mice lacking Npy were protected from both diabetic and non-diabetic kidney disease.

This, they say, suggested the local reduction of glomerular Npy was not causing a problem, but was a protective mechanism to reduce the amounts of local damaging Npy channelled to the kidney.

They then identified the precise signalling pathway of harm within the kidney and found it was happening via the Npy Receptor 2 (Npy-2R), which led them to giving the mice with kidney disease a drug to block the receptor. This resulted in the mice developing much less severe kidney disease.

Professor Coward said: “This is a hugely exciting breakthrough and shows that exploring and finding ways to stop Npy in its tracks really could take us one step closer to beating chronic kidney disease, along with a host of other debilitating conditions. We look forward to advancing this vital work in future research.”

Coward R et al. A novel role for NPY-NPY2R signalling in albuminuric kidney disease. PNAS 15 June 2020.

Tags: Internal Medicine | UK News

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