Blocking brain signals detected in the kidney may lead to kidney failure


Blocking brain signals detected in the kidney may lead to kidney failure

Journal of Nephrology and Urology is an Open Access peer-reviewed publication that discusses current research and advancements in diagnosis and management of kidney disorders as well as related epidemiology, pathophysiology and molecular genetics.

Scientists found Npy in cells called podocytes, which were sending harmful signals and damaging the filtering unit, known as the glomerulus. This caused large amounts of protein to leak into urine, a condition called proteinuria. Often undiagnosed early on, if left untreated the disorder can lead to kidney failure requiring dialysis or a kidney transplant and it is related to an increased risk of suffering a heart attack or stroke.

"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."

Initially the international collaborative study focused on diabetic kidney disease, the leading cause of kidney failure in the world. It revealed Npy was produced by the podocyte in the kidney as well as the brain. Furthermore, Npy production was massively reduced in diabetic podocyte cells studied in laboratory dishes and Npy levels were also significantly lower in the glomeruli of patients with diabetes.

To better understand the importance of Npy in the kidney, the research group studied mice that were both able and unable to produce Npy. Findings showed mice lacking Npy were protected from both diabetic and non-diabetic kidney disease. This suggested the local reduction of glomerular Npy initially observed was not causing a problem, but was in fact a protective mechanism to reduce the amounts of local damaging Npy channelled to the kidney.

Researchers went on to identify the precise signaling pathway of harm within the kidney, and found it was happening via a cell receptor called Npy Receptor 2 (Npy-2R). Having pinpointed the exact damaging pathway, they were determined to discover a way to stop it with medical intervention. So the mice with kidney disease were given a drug to block the Npy Receptor 2, which resulted in them developing much less severe kidney disease.

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