Scientists have identified a role for an enzyme critical to the body’s metabolism in the development of kidney disease, opening the door to new ways to prevent and treat this increasingly prevalent and potentially fatal condition. I got
According to the World Health Organization (WHO), kidney disease has risen from the 13th to the 10th leading cause of death. In 2019, 1.3 million people died from kidney disease, up from 813,000 in 2000. However, early detection and treatment can often slow or stop the progression of kidney disease to kidney failure.
Nicotinamide adenine dinucleotide (NAD+) is a coenzyme, a helper molecule found in all living cells. In addition to regulating various metabolic pathways, it is also involved in DNA repair and immune cell function. It is important for maintaining metabolic homeostasis (equilibrium) through its influence on mitochondria, the cell’s generators. Without sufficient levels of NAD+, cells cannot generate the energy they need to perform their metabolic functions.
Kidney tubular cells require a lot of mitochondrial-generated energy to perform their functions of reabsorbing essential nutrients and excreting waste products and toxins. When the mitochondria of these cells are damaged, it triggers an inflammatory response that can lead to kidney disease, causing fluid, electrolytes and waste products to build up in the body.
Now, researchers at the University of Pennsylvania have used metabolomics (the study of small molecules in blood and urine) to map metabolite changes in the kidneys of healthy and diseased mice and humans. Metabolites are very small molecules produced during metabolism. Measuring them provides insight into a person’s health. This is the first time that human samples have been used for metabolomics studies.
The researchers tested kidney samples from healthy controls against samples from patients with kidney disease due to diabetic kidney disease or high blood pressure (hypertension). They found that NAD+ levels were significantly lower in diseased kidneys. To investigate the disease mechanisms underlying these differences, they performed RNA sequencing of the samples.
Researchers who found a correlation between NAD+ levels and mitochondrial gene expression concluded that reduced NAD+ levels are a key feature of human kidney disease.
Furthermore, increasing NAD+ levels by feeding mice with a commercial supplement of the NAD+ precursors nicotinamide riboside or nicotinamide mononucleotide (NMN) protected mitochondria in renal tubular cells from damage, thereby contributing to renal disease. progress was prevented.
“We hope that this study will lead to improved care in the future,” said Katalin Sustak, co-first author of the study. “So if a patient develops a metabolite change, it can be treated before kidney damage occurs.”
The researchers hope their work will lead to further research into the role of metabolites in kidney disease and the development of new methods of prevention and treatment.
“Identifying these downstream mechanisms that are sensitive to NAD+ is critical to understanding what conditions NAD+ supplementation can improve,” said study co-first author Joseph Baur.
The study was published in a journal natural metabolism.
Source: University of Pennsylvania
