NAD + -Boosting Ameliorates Heme Protein-Mediated Acute Kidney Injury

Area of Science:

• Nephrology
• Biochemistry
• Mitochondrial Biology

Background:

• Heme proteins and heme induce acute kidney injury (AKI).
• A mouse model using glycerol demonstrates heme protein-mediated AKI (HP-AKI).
• Previous studies showed decreased NAD+ levels in HP-AKI.

Purpose of the Study:

• To investigate the therapeutic effect of NAD+-boosting in a mouse model of HP-AKI.
• To determine if nicotinamide mononucleotide (NMN) administration can mitigate kidney damage in HP-AKI.

Main Methods:

• Administered NMN to mice with glycerol-induced HP-AKI.
• Compared NMN treatment with vehicle control in HP-AKI and sham AKI mice.
• Assessed kidney function, histology, mitochondrial integrity, apoptosis, and senescence markers.

Main Results:

• NMN preserved kidney NAD+ levels in HP-AKI mice.
• NMN improved glomerular filtration and reduced histological injury.
• NMN decreased AKI markers (KIM1), preserved mitochondrial function, reduced apoptosis, and mitigated senescence.
• In vivo myoglobin or heme administration reduced kidney NAD+ in healthy mice.

Conclusions:

• NAD+-boosting with NMN demonstrates significant protective effects in HP-AKI across multiple markers.
• Reduced kidney NAD+ in HP-AKI may be due to direct effects of heme proteins or heme.
• These findings support NAD+-boosting as a potential therapeutic strategy for clinical AKI.