NAD+ Augmentation for Acute Kidney Injury

(NACAM Trial)

Overseen By Ali Poyan Mehr, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kaiser Permanente

Disqualifiers: Preexisting AKI, Kidney transplant, ESRD, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3 days

304 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Niacinamide for treating acute kidney injury?

Research suggests that boosting NAD+ levels, which Niacinamide is a part of, may help repair DNA damage and reduce inflammation in kidney cells, potentially improving outcomes after acute kidney injury. Additionally, Niacin, another form of vitamin B3 like Niacinamide, has shown protective effects on heart and kidney function in animal studies. ^{1 2 3 4 5}

Is NAD+ augmentation safe for humans?

Nicotinamide (a form of vitamin B3) and its related compounds, which help increase NAD+ levels, have been studied in various conditions and are generally considered safe in humans. However, specific safety data for acute kidney injury is limited, and more research is needed to confirm its safety in this context. ^{1 3 4 5 6}

How does the drug Niacinamide differ from other treatments for acute kidney injury?

Niacinamide is unique because it aims to boost NAD+ levels, which may help repair kidney damage by improving DNA repair and reducing inflammation. This approach is different from other treatments that do not focus on enhancing NAD+ to protect the kidneys. ^{1 3 4 5 7}

What is the purpose of this trial?

A Randomized, Double-blind, placebo-controlled Trial to Evaluate the Efficacy of Oral Nam for the Prevention of Acute Kidney Injury in Patients Undergoing On-Pump Cardiac Surgery

Eligibility Criteria

This trial is for adults over 18 who need non-emergency heart surgery with a pump and are at high risk of heart-related complications. Eligible participants include those with valve surgeries, weak kidney function, reduced heart pumping capacity, history of heart failure or diabetes, protein in urine, anemia, previous bypass surgery or age 65+.

Inclusion Criteria

You have certain health conditions or risk factors that could make surgery risky for your heart, such as heart valve surgery, kidney function below a certain level, weak heart pumping function, history of heart failure, diabetes requiring insulin, diabetes not requiring insulin with certain kidney function test results, low red blood cell count, previous heart bypass surgery, or being 65 years or older.

Informed consent before any study-related activities

I have had heart surgery, including valve repair or replacement.

Exclusion Criteria

I have had a kidney transplant.

I am having heart surgery without using a heart-lung machine.

My kidney function was reduced before surgery, as shown by a creatinine test.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Nam 3 grams or placebo on the day of surgery and post-surgical days one and two

3 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• Niacinamide
• Placebo

Trial Overview The study tests if Niacinamide (a form of vitamin B3) can prevent acute kidney injury after on-pump cardiac surgery compared to a placebo. Participants will be randomly assigned to receive either Niacinamide or a placebo in this double-blind study where neither the patients nor the researchers know who gets which treatment.

Participant Groups

Group I: Oral niacinamide Experimental Treatment 1 Intervention

Group II: Matched placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Kaiser Permanente

Lead Sponsor

Trials

563

Recruited

27,400,000+

Beth Israel Deaconess Medical Center

Collaborator

Trials

872

Recruited

12,930,000+

Cedars-Sinai Medical Center

Collaborator

Trials

523

Recruited

165,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

In patients undergoing cardiac bypass surgery, lower levels of urine tryptophan and kynurenine were linked to the development of acute kidney injury (AKI), indicating a potential issue with the kynurenine pathway involved in NAD+ synthesis.

Despite the expectation that nicotinamide (NAM) supplementation would improve kidney health by replenishing NAD+, it did not enhance kidney NAD+ levels or improve kidney function in mouse models of ischemic-reperfusion injury, suggesting that the effectiveness of vitamin B3 derivatives in treating kidney injury may vary and requires further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide and acute kidney injury. Fontecha-Barriuso, M., Lopez-Diaz, AM., Carriazo, S., et al.[2021]

In a study involving male Sprague-Dawley rats, niacin treatment before and after kidney ischemia and reperfusion significantly improved cardiac function and reduced oxidative stress, indicating its protective role during kidney injury.

The results suggest that kidney I/R injury leads to cardiac dysfunction through increased lipid peroxidation and altered energy production, while niacin helps sustain mitochondrial metabolism and PGC-1α expression, which is crucial for ATP production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niacin ameliorates kidney warm ischemia and reperfusion injury-induced ventricular dysfunction and oxidative stress and disturbance in mitochondrial metabolism in rats. Tai, ST., Fu, YH., Yang, YC., et al.[2018]

In a study of 167 cardiac bypass surgery patients, a significant decrease in urinary tryptophan and kynurenin was observed in those who developed acute kidney injury (AKI), indicating a potential biomarker for AKI risk.

However, supplementation with nicotinamide (NAM) did not improve kidney function or outcomes in a mouse model of ischaemic AKI, suggesting that NAM may not be an effective treatment for preventing renal damage in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The tryptophan pathway and nicotinamide supplementation in ischaemic acute kidney injury. Piedrafita, A., Balayssac, S., Mayeur, N., et al.[2022]

Administration of NMN, a precursor to NAD+, significantly reduced DNA damage and cellular senescence in human kidney cells exposed to harmful conditions, suggesting its protective effects against acute kidney injury (AKI).

In mouse models of ischemic AKI, NMN demonstrated antifibrotic properties, effectively preventing kidney fibrosis whether given before or during recovery, indicating its potential as a therapeutic strategy for kidney repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Mononucleotide Attenuates Renal Interstitial Fibrosis After AKI by Suppressing Tubular DNA Damage and Senescence. Jia, Y., Kang, X., Tan, L., et al.[2021]

The study identified that the urinary ratio of quinolinic acid (QA) to 3-hydroxyanthranilic acid (3-OH AA) can predict acute kidney injury (AKI) in two cohorts, with AUC values of 0.749 and 0.729, indicating a moderate predictive ability.

Human proximal tubules were found to be the main site for NAD+ de novo synthesis, and a decrease in the enzyme HAAO, which is involved in this process, was linked to a higher risk of AKI, suggesting a potential biomarker for early detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The metabolites of de novo NAD+ synthesis are a valuable predictor of acute kidney injury. Wang, Y., Guan, Y., Xie, Q., et al.[2023]

Supplementation with nicotinamide (Nam), a precursor of NAD+, significantly reduced kidney inflammation and fibrosis in a mouse model of chronic kidney disease (CKD), suggesting it may help prevent disease progression.

Nam supplementation also decreased the buildup of harmful metabolites associated with renal failure by enhancing NAD+ levels, which supports metabolic pathways that are crucial for kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney Disease. Kumakura, S., Sato, E., Sekimoto, A., et al.[2021]

A new NAD+ precursor called NMNH has been synthesized, which significantly increases NAD+ levels more effectively and rapidly than existing precursors like NMN and NR, using a unique metabolic pathway.

In studies with mice, NMNH not only caused a quick surge in NAD+ levels across various organs but also demonstrated protective effects against kidney damage from hypoxia, suggesting its potential as a therapeutic option for acute kidney injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced nicotinamide mononucleotide is a new and potent NAD+ precursor in mammalian cells and mice. Zapata-Pérez, R., Tammaro, A., Schomakers, BV., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Nicotinamide and acute kidney injury. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Niacin ameliorates kidney warm ischemia and reperfusion injury-induced ventricular dysfunction and oxidative stress and disturbance in mitochondrial metabolism in rats. [2018]

3. England pubmed.ncbi.nlm.nih.gov

The tryptophan pathway and nicotinamide supplementation in ischaemic acute kidney injury. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Nicotinamide Mononucleotide Attenuates Renal Interstitial Fibrosis After AKI by Suppressing Tubular DNA Damage and Senescence. [2021]

5. England pubmed.ncbi.nlm.nih.gov

The metabolites of de novo NAD+ synthesis are a valuable predictor of acute kidney injury. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney Disease. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Reduced nicotinamide mononucleotide is a new and potent NAD+ precursor in mammalian cells and mice. [2021]