Could vitamin B3 treat acute kidney injury?

August 20, 2018, Beth Israel Deaconess Medical Center
Credit: CC0 Public Domain

Acute kidney injury, an often fatal condition without a specific treatment, affects up to 10 percent of all hospitalized adults in the United States and 30-40 percent in low-income countries. The condition causes a build-up of waste products in the blood and an imbalance of fluids throughout the body. Acute kidney injury can occur from ailments that place the body into extreme stress—putting already hospitalized patients, particularly those in intensive care units, at risk.

A multidisciplinary research team led by Beth Israel Deaconess Medical Center nephrologist and principal investigator Samir M. Parikh, MD, has now determined that a form of vitamin B3 has the potential to prevent acute injury. Published today in Nature Medicine, the findings bring clinicians one step closer to an accessible and safe therapy for who may be at risk.

Parikh and colleagues discovered that levels of (NAD+) - the end result of vitamin B3 after it is ingested—declines in cases of acute kidney injury.

"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," said Parikh, who is also an Associate Professor of Medicine at Harvard Medical School. "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."

Parikh—along with first authors Mei Tran, a senior scientist in the Parikh laboratory, and Ali Poyan Mehr, MD, a nephrologist at BIDMC—made the discovery by studying the metabolic changes associated with acute kidney injury in a mouse model. A urine screen revealed high levels of quinolinate—a little-studied intermediate for making NAD+. This unusual pattern suggested a block at an enzyme called QPRT which is responsible for converting quinolinate to NAD+. With QPRT blocked, an explanation began to emerge for NAD+ depletion during acute kidney injury, which disrupts the body's ability to manufacture NAD+.

The scientists tested that hypothesis by using CRISPR gene editing to create a with reduced QRPT but no kidney injury. The genetically altered rodents mimicked the pattern of acute kidney injury; decreased NAD+, increased urinary quinolinate and increased susceptibility to kidney injury. The experiments were the first to establish QRPT as a mediator of renal stress resistance.

In subsequent human studies, the team found high urinary quinolinate in patients undergoing major surgery at risk for acute kidney injury and confirmed this metabolite pattern in a separate study of 329 patients also at risk for acute kidney injury. The team then gave large doses of oral vitamin B3 to 41 cardiac surgery patients enrolled in a Phase 1 pilot study.

"Our results suggest that NAD+ biosynthesis becomes impaired during human acute kidney and that augmenting vitamin B3 levels may be safe and potentially beneficial to patients." said Kamal Khabbaz, MD, Chief of Cardiac Surgery at the CardioVascular Institute at BIDMC, who co-led the clinical trial. "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 , though further studies are needed to verify these findings."

Explore further: Hospitalized patients with acute kidney injury have increased risk of heart failure

More information: De novo NAD+ biosynthetic impairment in acute kidney injury in humans, Nature Medicine (2018). DOI: 10.1038/s41591-018-0138-z , www.nature.com/articles/s41591-018-0138-z

Related Stories

Hospitalized patients with acute kidney injury have increased risk of heart failure

May 18, 2018
Hospitalized patients who experience acute kidney injury face a 44 percent greater risk of heart failure during their first year after leaving the hospital, according to new Kaiser Permanente research published today in the ...

ASN: Severe acute kidney injury ups risk of 28-day mortality

November 21, 2016
(HealthDay)—Acute kidney injury is associated with increased risk of 28-day mortality among critically ill children and young adults, according to a study published online Nov. 18 in the New England Journal of Medicine. ...

Study finds acetaminophen helps reduce acute kidney injury risk in children following cardiac surgery

May 21, 2018
Children who underwent cardiac surgery were less likely to develop acute kidney injury if they had been treated with acetaminophen in the first 48 hours after their procedures, according to a Vanderbilt study just published ...

Model predicts development of chronic kidney disease

November 16, 2017
(HealthDay)—A multivariable model that uses routine laboratory data is able to predict advanced chronic kidney disease after hospitalization with acute kidney injury, according to a study published online Nov. 14 in the ...

Caffeine found to reduce incidence of acute kidney injury in neonates

April 3, 2018
Preterm neonates who are exposed to caffeine within the first seven days after birth have reduced incidence and severity of acute kidney injuries than neonates who did not, according to findings from the Neonatal Kidney Collaborative's ...

Scientists confirm better test for acute kidney injury in children

April 7, 2015
Yale researchers compared two markers for acute kidney injury (AKI), an increasingly common condition affecting thousands of hospitalized patients each year. The Yale team members and their co-authors found that a less commonly ...

Recommended for you

Researchers discover important connection between cells in the liver

November 15, 2018
University of Minnesota Medical School researchers have made a discovery which could lead to a new way of thinking about how disease pathogenesis in the liver is regulated, which is important for understanding the condition ...

Gut hormone and brown fat interact to tell the brain it's time to stop eating

November 15, 2018
Researchers from Germany and Finland have shown that so-called "brown fat" interacts with the gut hormone secretin in mice to relay nutritional signals about fullness to the brain during a meal. The study, appearing November ...

Brain, muscle cells found lurking in kidney organoids grown in lab

November 15, 2018
Scientists hoping to develop better treatments for kidney disease have turned their attention to growing clusters of kidney cells in the lab. One day, so-called organoids—grown from human stem cells—may help repair damaged ...

How the Tasmanian devil inspired researchers to create 'safe cell' therapies

November 15, 2018
A contagious facial cancer that has ravaged Tasmanian devils in southern Australia isn't the first place one would look to find the key to advancing cell therapies in humans.

Precision neuroengineering enables reproduction of complex brain-like functions in vitro

November 14, 2018
One of the most important and surprising traits of the brain is its ability to dynamically reconfigure the connections to process and respond properly to stimuli. Researchers from Tohoku University (Sendai, Japan) and the ...

Gene mutation found to cause macrocephaly and intellectual deficits

November 13, 2018
The absence of one copy of a single gene in the brain causes a rare, as-yet-unnamed neurological disorder, according to new research that builds on decades of work by a University at Buffalo biochemist and his colleagues.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.