Nicotinamide Riboside Protects Against Diabetic Kidney Disease: Preclinical Findings

Synopsis

Diabetic kidney disease (DKD) is a leading cause of kidney failure, linked to inflammation and mitochondrial dysfunction. This study evaluated whether boosting NAD+ metabolism via nicotinamide riboside (NR) supplementation could prevent DKD progression in db/db mice, a type 2 diabetes model. NR treatment significantly reduced markers of kidney damage including albuminuria and urinary KIM1. This renoprotection was associated with decreased inflammation, notably by inhibiting the cGAS-STING pathway, which senses mitochondrial DNA leakage. NR enhanced activity of the mitochondrial deacetylase SIRT3, improving mitochondrial function and reducing mitochondrial DNA damage. Pharmacological inhibition or genetic deletion of STING similarly protected kidneys, supporting the central role of this pathway. These findings demonstrate that NR boosts NAD+ metabolism to improve mitochondrial health and suppress inflammation, thereby preventing DKD progression.

Journal

Journal of Biological Chemistry