Vitamin B3 could potentially treat kidney injury

A research team has identified that a form of vitamin B3 may prevent acute kidney injury.

The multidisciplinary research team led by nephrologist, Principle Investigator and Associate Professor at Harvard Medical School, Dr Samir Parikh from the Beth Israel Deaconess Medical Centre (BIDMC), found that levels of nicotinamide adenine dinucleotide (NAD+) declines in cases of acute kidney injury. NAD+ is the end product after vitamin B3 is ingested.

Acute kidney injury affects up to 10 percent of all hospitalised adults in America. It is often fatal and causes a build-up of waste products in the blood and an imbalance of fluids throughout the body. The disease can occur when the body is in extreme stress, usually from other ailments. This puts already hospitalised patients at further risk.

Prof Parikh said: “We were able to detect a drop in NAD+ in the urine of high-risk patients who were either in an intensive care unit or undergoing a major surgery and found that oral vitamin B3 could safely elevate NAD+ in high-risk patients.

“These findings are very early, but the results suggest that we could one day have a non-invasive test for NAD+ status and perhaps even treat acute kidney injury by boosting NAD+ levels.”

The research team investigated the metabolic changes associated with acute kidney injury in a mouse model. After screening urine, they identified high levels of quinolinate – an intermediate for making NAD+.

The analyses led the team to believe the enzyme QPRT was blocked. This enzyme is responsible for converting quinolinate to NAD+. Thus, the scientist explained how levels of NAD+ decreased during acute kidney injury.

Using CRISPR gene editing, the researcher created a mouse model with reduced QRPT, but no kidney injury. These genetically altered mice mimicked the pattern of the disease with decreased NAD+, increased urinary quinolinate and increased susceptibility to kidney injury. These experiments identified QRPT as a mediator of renal stress resistance.

The researchers carried out subsequent human studies and found high levels of urinary quinolinate in patients undergoing major surgery. They confirmed the metabolite pattern in a separate study of 329 intensive care unit patients. The patients were then given large doses of oral vitamin B3 in a Phase I pilot study.

“Our results suggest that NAD+ biosynthesis becomes impaired during human acute kidney injury and that augmenting vitamin B3 levels may be safe and potentially beneficial to patients,” said Chief of Cardiac Surgery at the Cardiovascular Institute at BIDMC, Dr Kamal Khabbaz.

“What’s more, we showed that urinary measurements in at-risk patients can indicate this impairment and, furthermore, predict adverse outcomes. Restoring NAD+ could constitute and important advance for patients at risk for acute kidney injury, though further studies are needed to verify these findings.”

The study was published in Nature Medicine.