Researchers at the University of South Australia have identified enzymes that may help control chronic kidney disease, which affects about 700 million people worldwide.
The enzyme NEDD4-2 is important for kidney health, said Dr. Jantina Manning, a scientist at the UniSA Center for Cancer Biology, in a new paper published this month. Cell death and disease..
Early career researchers, including Professor Sharad Kumar of the 2020SA Scientist of the Year, and her colleagues have shown a correlation between high-salt diets, low levels of NEDD4-2, and advanced kidney disease in animal studies.
High-salt diets can exacerbate certain kidney diseases, but until now, researchers were unaware that NEDD4-2 played a role in promoting this salt-induced kidney damage.
“Both high-sodium diets and low NEDD4-2 levels have been shown to promote the progression of kidney disease, even in the absence of hypertension, which is usually closely associated with increased sodium,” said Dr. Manning. I will.
NEDD4-2 regulates the pathways required for sodium reabsorption in the kidneys to maintain the correct levels of salt. When NEDD4-2 protein is reduced or inhibited, increased salt absorption can cause kidney damage.
Even people on a low-salt diet can have kidney damage if their NEDD4-2 levels are low due to genetic or genetic mutations.
Professor Kumar says the long-term goal is to develop drugs that can increase NEDD4-2 levels in people with chronic kidney disease (CKD).
“Currently, we are testing various strategies to ensure that this protein is always maintained at normal levels for the health of the entire kidney,” says Professor Kumar.
“In diabetic nephropathy, a common cause of kidney disease, NEDD4-2 levels are significantly reduced, even if salt is not a factor.”
The study also revealed a surprising finding: kidney disease induced by a high-salt diet is not necessarily due to high blood pressure.
“In many cases, kidney disease is exacerbated by high blood pressure, so we wanted to investigate its association in a study. In fact, we found the complete opposite that the high-salt diet caused excessive water loss and hypotension. This is important because it means that kidney disease can also occur in people without high blood pressure, “says Dr. Manning.
2020 Lancet According to the paper, about 700 million people, or 10% of the world’s population, suffer from chronic kidney disease, an increase of 29% over the last 30 years.
The significant surge in CKD is primarily due to the global obesity epidemic of recent decades, causing hypertension as well as diabetes, which is one of the leading causes of chronic kidney disease.
According to World Health Organization statistics, diabetes increased by 300% between 1980 and 2014, making it one of the top 10 causes of death in the world, and the seriousness of the problems faced by scientists working on kidney disease. is showing.
“Obesity and lifestyle are the two main factors that cause chronic kidney disease, but there are other implications,” says Dr. Manning. “Acute kidney injury, medications taken for other symptoms, high blood pressure, and genetic predisposition can also cause it.”
Mayo Clinic Minutes: What is Chronic Kidney Disease?
Jantina A. Manning et al. Ubiquitin ligase NEDD4-2 / NEDD4L regulates both sodium homeostasis and fibrotic signaling to prevent end-stage renal disease. Cell death and disease (2021). DOI: 10.1038 / s41419-021-03688-7
Courtesy of the University of South Australia
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Enzymes that can help 700 million people around the world
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