Nicotinamide Riboside and Nicotinamide Mononucleotide Protect Against Kidney Injury: Preclinical Findings

Synopsis

This study uncovered how NAD+ deficiency contributes to kidney disease by damaging mitochondria and triggering inflammation. Through metabolic analysis of human kidney samples, researchers identified low NAD+ as a hallmark of kidney damage. In mouse models of cisplatin-induced and ischemia-reperfusion kidney injury, NAD+ levels dropped sharply, leading to mitochondrial dysfunction and the leakage of mitochondrial RNA (mtRNA) into the cell cytoplasm. This mtRNA leakage activated the RIG-I pathway, a defense mechanism that worsened inflammation and kidney injury. Supplementing with nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN) replenished NAD+ levels, restored mitochondrial function, and prevented RIG-I activation, protecting kidney health. Mice lacking RIG-I were naturally resistant to kidney damage, confirming this pathway’s key role. The findings suggest that boosting NAD+ with NR or NMN can block a mitochondrial-driven inflammatory process and may serve as a promising therapy for kidney injury.

Journal

Nature Metabolism