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

Toxins (Basel). 2021 Jan 11;13(1):50. doi: 10.3390/toxins13010050.

Abstract

Nicotinamide adenine dinucleotide (NAD+) supplies energy for deoxidation and anti-inflammatory reactions fostering the production of adenosine triphosphate (ATP). The kidney is an essential regulator of body fluids through the excretion of numerous metabolites. Chronic kidney disease (CKD) leads to the accumulation of uremic toxins, which induces chronic inflammation. In this study, the role of NAD+ in kidney disease was investigated through the supplementation of nicotinamide (Nam), a precursor of NAD+, to an adenine-induced CKD mouse model. Nam supplementation reduced kidney inflammation and fibrosis and, therefore, prevented the progression of kidney disease. Notably, Nam supplementation also attenuated the accumulation of glycolysis and Krebs cycle metabolites that occurs in renal failure. These effects were due to increased NAD+ supply, which accelerated NAD+-consuming metabolic pathways. Our study suggests that Nam administration may be a novel therapeutic approach for CKD prevention.

Keywords: CKD; Krebs cycle; NAD+; adenine-induced CKD model; glycolysis; nicotinamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine
  • Animals
  • Citric Acid Cycle
  • Disease Models, Animal
  • Disease Progression
  • Energy Metabolism
  • Glycolysis
  • Kidney / metabolism
  • Male
  • Metabolic Networks and Pathways
  • Metabolome
  • Mice
  • Mice, Inbred C57BL
  • NAD / metabolism*
  • Niacinamide / therapeutic use*
  • Renal Insufficiency / drug therapy*
  • Renal Insufficiency, Chronic / chemically induced
  • Renal Insufficiency, Chronic / drug therapy*

Substances

  • NAD
  • Niacinamide
  • Adenine