Impact of Nicotinamide Riboside (NR) on Kidney Function in Patients Undergoing Cardiac Surgery (AKI-RCT)

National Institute of Cardiology Ignacio Chavez

Status

Not yet enrolling

Conditions

Acute Kidney Injury

Cardiac Valve Disease

Treatments

Other: Placebo

Dietary Supplement: Nicotinamide riboside

Study type

Interventional

Funder types

Other

Identifiers

NCT06521307

SIRT1-NR.AKI

Details and patient eligibility

About

Acute kidney injury (AKI) associated with cardiac surgery is the most important complication in adult patients undergoing open heart surgery and is associated with increased mortality and morbidity. In patients in intensive care units, it is the second most common type of AKI after AKI secondary to sepsis. There is currently no specific treatment for AKI. Supportive measures include renal support therapy for patients with severe AKI, and mortality in this subgroup of patients exceeds 50%. Increasing NAD+ with niacinamide has been shown to prevent various etiologies of experimental AKI in mice, and an early pilot study has shown both increased NAD levels following administration of nicotinamide riboside with pterostilbene NPRT and the safety of niacinamide in patients undergoing cardiac surgery.

Full description

AKI associated with cardiac surgery is a condition with a high incidence of morbidity and mortality, without pharmacological interventions approved for its prevention or treatment. As far as we know, there is no study that evaluates the impact of the administration of nicotinamide riboside on renal function in patients undergoing cardiac surgery.

Implementation of this relatively low-cost intervention and adequate safety profile would reduce in-hospital complications in risk patients undergoing cardiac surgery.

Nicotinamide adenine dinucleotide (NAD+) is a cellular factor related to metabolism and longevity. NAD+ is a required cofactor of SIRT1, a nuclear deacetylase that modulates chromatin structure, gene expression, prolongs lifespan in organisms, and ameliorates age-related diseases. Experimental AKI in mice rapidly leads to reduced NAD+ levels in the kidney resulting from a combination of decreased NAD+ biosynthesis and increased NAD+ consumption. Likewise, mice deficient in SIRT1 are more susceptible to AKI and when there is overexpression of SIRT1 they are protected from AKI. These studies describe the modulation of NAD+ and SIRT1 as a potential therapeutic approach in AKI. Similarly, in subjects with AKI, there is evidence of a 50% reduction in plasma NAD. Increasing NAD+ with niacinamide has been shown to prevent various etiologies of experimental AKI in mice, and an early pilot study has shown both increased NAD levels following administration of nicotinamide riboside with pterostilbene NPRT and the safety of niacinamide in patients undergoing cardiac surgery.

Enrollment

100 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Heart valve replacement surgery
Sign of informed consent

Exclusion criteria

Allergy to any of the components
Platelet count less than 100,000
Weight less than 50Kg or over 100Kg
Any type of infectious disease (e. g, Endocarditis)
GFR less or equal to 15ml/min/m2 or with renal replacement therapy
IV or oral contrast medium 72 hrs prior recruitment
LRA 7 days prior to surgery

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

100 participants in 2 patient groups, including a placebo group

Riboside (RN) arm

Experimental group

Description:

NAD Riboside 2000 mg by oral intake at enrollment 24hrs prior surgery, 3000mg prior undergoing surgery with NG tube, 3000mg 12 hrs post-surgery with NG tube and 2000mg 24 hrs after intervention by oral intake.

Treatment:

Dietary Supplement: Nicotinamide riboside

Placebo arm

Placebo Comparator group

Description:

Treatment:

Other: Placebo