Study summary · research use only
NAD(+) precursor supplementation prevents mtRNA/RIG-I-dependent inflammation during kidney injury
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This study combined metabolomic analysis of healthy and diseased human kidney tissue with experiments in male mice models of cisplatin- or ischaemia-reperfusion-induced kidney injury. The authors identified nicotinamide adenine dinucleotide (NAD+) deficiency as a signature of human kidney disease and observed NAD+ depletion in the mouse injury models. Supplementation with nicotinamide riboside or nicotinamide mononucleotide was associated with restored NAD+ levels and improved kidney function measures in mice. Cisplatin exposure was associated with cytosolic leakage of mitochondrial RNA (mtRNA) and activation of the RIG-I receptor, both reduced by restoring NAD+, and RIG-I knockout male mice showed reduced cisplatin-induced kidney disease. The authors describe cytosolic mtRNA release and RIG-I activation as an NAD+-sensitive mechanism linked to kidney disease in this study.
Abstract
Our understanding of how global changes in cellular metabolism contribute to human kidney disease remains incompletely understood. Here we show that nicotinamide adenine dinucleotide (NAD+) deficiency drives mitochondrial dysfunction causing inflammation and kidney disease development. Using unbiased global metabolomics in healthy and diseased human kidneys, we identify NAD+ deficiency as a disease signature. Furthermore using models of cisplatin- or ischaemia-reperfusion induced kidney injury in male mice we observed NAD+ depletion Supplemental nicotinamide riboside or nicotinamide mononucleotide restores NAD+ levels and improved kidney function. We find that cisplatin exposure causes cytosolic leakage of mitochondrial RNA (mtRNA) and activation of the cytosolic pattern recognition receptor retinoic acid-inducible gene I (RIG-I), both of which can be ameliorated by restoring NAD+. Male mice with RIG-I knock-out (KO) are protected from cisplatin-induced kidney disease. In summary, we demonstrate that the cytosolic release of mtRNA and RIG-I activation is an NAD+-sensitive mechanism contributing to kidney disease.
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