Acute Kidney Injury, Cardiac Valve Disease
Conditions
Keywords
Nicotinamide Riboside, NAD+, NADH, SIRT1, AKI, Cardiac surgery, TIMP-2, IGFBP7, NGAL
Brief summary
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.
Detailed 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.
Interventions
DIETARY_SUPPLEMENTNicotinamide riboside
We will recruit the participant 24 hrs prior intervention, once the participant decides to enroll, we will administer by oral intake the supplement or placebo due to the result at randomizer.org. The first NAD Riboside arm will be administered by oral intake with 2000 mg at enrollment, then we will administer 3000mg prior undergoing surgery with NG tube, 3000mg 12 hrs post-surgery with NG tube and 2000mg by oral intake 24 hrs after intervention. All the administrations with NG tube will be flushed with 0.9% saline solution.
OTHERPlacebo
We will recruit the participant 24 hrs prior intervention, once the participant decides to enroll, we will administer by oral intake the supplement or placebo due to the result at randomizer.org. The first dose of placebo arm will be administered by oral intake with 2000 mg at enrollment, then we will administer 3000mg prior undergoing surgery with NG tube, 3000mg 12 hrs post-surgery with NG tube and 2000mg by oral intake 24 hrs after intervention. All the administrations with NG tube will be flushed with 0.9% saline solution.
Sponsors
Instituto Nacional de Cardiologia Ignacio Chavez
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
The protocol contemplates triple blinding for the intervention. The inclusion and follow-up of patients will be carried out by the team of clinical investigators, who will remain blinded to the assigned group. Assignment to intervention groups will be carried out by an investigator independent of the team of clinical investigators and the clinical management team, who will remain blind to the information and follow-up of the patients. The medical team in charge of hospital treatment (surgery, cardiology, intensive care and nephrology), and the patient himself will remain blind to the assigned intervention group.
Intervention model description
The evaluation of normality will be carried out by the Shapiro-Wilks and Kolmogorov-Smirnov tests. The change or delta in the creatinine value from preoperative to 48 hours postoperative will be calculated, said delta will be analyzed with a t-test between the intervention groups. Other variables will also be compared between groups with t-test or U-Mann-Whitney for quantitative variables. Qualitative variables will be analyzed with a Chi-square test between groups. In secondary objectives, biochemical measurements will be correlated with creatinine values with the Pearson or Spearman test as appropriate to the distribution. Statistical package= SPSS version 23. Statistical significance= alpha 0.05
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Impact of nicotinamide riboside (NR) on kidney function in patients undergoing cardiac surgery. | 2 years | The NAD+ and NADH will be measured with the quantitation of the cofactor SIRT1 with a human SIRT1 ELISA kit (novus, NBP2-80300) and a fluorogenic assay SIRT1 CS1040 and flow cytometry. |
Countries
Mexico
Contacts
Primary ContactMagdalena Madero, MD
Backup ContactAna K. Fernandez, MD
Outcome results
None listed