A deficiency of an important enzyme in the body causes kidney disease

According to New Atlas, a team of University of Pennsylvania scientists has identified a role for an enzyme called nicotinamide adenine dinucleotide (NAD+) in kidney disease. New Atlas Cited from Nature Metabolism.

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. But if kidney disease is detected and treated early, it is often possible to slow or stop kidney failure.

Revealing

Metabolic balance

NAD+ coenzyme Nicotinamide adenine dinucleotide is a coenzyme found in every cell that regulates various metabolic pathways, as well as being involved in DNA repair and immune cell function. It is essential to maintain metabolic balance through its effect on the mitochondria, the energy generators in the cell, and without adequate amounts of enzymes, the body’s cells cannot generate the energy they need to perform their metabolic functions.

Tubular cells in the kidneys need a lot of energy produced by mitochondria to perform their function, reabsorb essential nutrients and excrete waste and toxins. When the mitochondria in these cells are damaged, an inflammatory response is triggered that leads to kidney disease, which causes the body to build up fluid, electrolytes, and waste products.

Human models for the first time

In the new study, researchers used metabolomics, a study of small molecules found in blood and urine, to map metabolic changes in human kidneys. It gives the amount of metabolites, which are very small molecules produced during metabolism; Insights into a person’s health. This is the first time that human models have been used in metabolomics studies.

Kidneys

The underlying disease mechanism

The researchers tested kidney samples from a healthy control group against samples from patients with diabetic kidney disease or kidney disease caused by high blood pressure. It turns out that NAD+ levels are significantly lower in diseased kidneys. To investigate the disease mechanism underlying these differences, they performed RNA-sequencing of the samples.

Prevents kidney damage

The researchers sought to determine the relationship between NAD+ levels and mitochondrial gene expression, and concluded that low NAD+ levels are a key feature of human kidney disease. Furthermore, when laboratory mice were given over-the-counter supplements of the NAD+ precursor nicotinamide riboside or nicotinamide mononucleotide (NMN) to increase NAD+ levels, tubular cell mitochondria were protected from damage and prevented the development of kidney disease.

Developing treatment regimens

The principal investigator of the study, Katalin Sostak, believes that “this research will lead to improved care in the future, so that if patients have metabolic changes, they can be treated before kidney disorders become apparent.”

The researchers hope that their study will lead to further studies of the role of metabolites in kidney disease and the development of new approaches to prevention and treatment.

“Identifying NAD+-sensitive downstream mechanisms is critical to understanding conditions that may benefit from NAD+ supplementation,” said study co-author Joseph Bauer.

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