Abstract: FR-OR05
Nicotinamide Riboside with Pterostilbene Increases NAD+ in Patients with AKI: A Randomized, Double-Blind, Placebo-Controlled, Stepwise Safety Study of NRPT in Patients with AKI
Session Information
- AKI Predictors and Outcomes: Research Abstracts
October 23, 2020 | Location: Simulive
Abstract Time: 05:00 PM - 07:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Simic, Petra, Massachusetts General Hospital, Boston, Massachusetts, United States
- Parada, Xavier F., Massachusetts General Hospital, Boston, Massachusetts, United States
- Parikh, Samir M., Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
- Dellinger, Ryan, Elysium Inc, New York, New York, United States
- Guarente, Leonard P., Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
- Rhee, Eugene P., Massachusetts General Hospital, Boston, Massachusetts, United States
Background
Preclinical studies have identified both NAD+ and sirtuin augmentation as potential strategies for the prevention and treatment of AKI. Nicotinamide riboside (NR) is a NAD+ precursor vitamin and pterostilbene (PT) is potent sirtuin activator found in blueberries. Here, we tested the effect of combined NR and PT (NRPT) on whole blood NAD+ levels and safety parameters in patients with AKI.
Methods
We conducted a randomized, double-blind, placebo-controlled study of escalating doses of NRPT in 24 hospitalized patients with AKI. The study was comprised of four Steps during which NRPT (5 subjects) or placebo (1 subject) was given twice a day for two days. NRPT dosing was increased in each Step: Step 1 250/50mg, Step 2 500/100mg, Step 3 750/150mg and Step 4 1000/200mg. Blood NAD+ levels were measured by liquid chromatography-mass spectrometry and safety was assessed by history, physical exam, and clinical laboratory testing.
Results
AKI resulted in a 50% reduction in whole blood NAD+ levels at 48 hr compared to 0 hr in patients receiving placebo (p=0.05). There was a trend for increase in NAD+ levels in all NRPT Steps individually at 48 hr compared to 0 hr, but only the change in Step 2 reached statistical significance (47%, p=0.04), and there was considerable interindividual variability in the NAD+ response to treatment. Considering all Steps together, NRPT treatment increased NAD+ levels by 37% at 48hr compared to 0hr (p=0.002). All safety laboratory tests were unchanged by NRPT treatment, including creatinine, estimated glomerular filtration rate (eGFR), electrolytes, liver function tests, and blood counts. Three of 20 patients receiving NRPT reported minor gastrointestinal side effects.
Conclusion
NRPT increases whole blood NAD+ levels in hospitalized patients with AKI. In addition, NRPT up to a dose of 1000mg/200mg twice a day for two days is safe and well tolerated in these patients. Further studies to assess the potential therapeutic benefit of NRPT in AKI are warranted.
Funding
- Commercial Support –