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.
Highlights
Chronic kidney disease (CKD) is a worldwide burden affecting approximately 10%of the global population [1,2,3]
We demonstrated that the prophylactic administration of Nam to a mouse model of adenine-induced CKD prevented the progression of kidney disease
A previous study on unilateral ureteral obstruction (UU’O) has shown that Nam administration before UU’O surgery prevents renal fibrosis by reducing the inflammation caused by IL-1 beta [23], which supports our results that continuous Nam administration prevents inflammation and fibrosis of kidney
Summary
Of the global population [1,2,3]. Patients with CKD have a high risk of cardiovascular events [4,5], infection [6,7], and malignancy [8,9]. Few studies have addressed the therapeutic relevance of NAD+ in CKD [23]. A distinct mechanism, the salvage pathway, results in NAD+ synthesis from nicotinamide (Nam), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN), which derive from NAD+ metabolism. Several studies have explored the effects of salvage pathway stimulation by the administration of Nam, NR, and NMN. These investigations have focused on the activation of sirtuins induced by increased NAD+ levels. The therapeutic relevance of Nam in CKD is not well established To address this issue, we explored the effects of Nam in an adenine-induced CKD mouse model by using a metabolomics approach
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