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

Satoshi Kumakura; Emiko Sato; Akiyo Sekimoto; Yamato Hashizume; Shu Yamakage; Mariko Miyazaki; Sadayoshi Ito; Hideo Harigae; Nobuyuki Takahashi

doi:10.3390/TOXINS13010050

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

Satoshi Kumakura, Emiko Sato, Akiyo Sekimoto, Yamato Hashizume, Shu Yamakage, Mariko Miyazaki, Sadayoshi Ito, Hideo Harigae, Nobuyuki Takahashi

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

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.

Original language	English
Article number	50
Journal	Toxins
Volume	13
Issue number	1
DOIs	https://doi.org/10.3390/TOXINS13010050
Publication status	Published - 2021 Jan

Keywords

CKD
Krebs cycle
NAD
adenine-induced CKD model
glycolysis
nicotinamide

ASJC Scopus subject areas

Toxicology
Health, Toxicology and Mutagenesis

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10.3390/TOXINS13010050

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

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",

author = "Satoshi Kumakura and Emiko Sato and Akiyo Sekimoto and Yamato Hashizume and Shu Yamakage and Mariko Miyazaki and Sadayoshi Ito and Hideo Harigae and Nobuyuki Takahashi",

note = "Funding Information: Funding: This study was funded by JSPS KAKENHI (Grant Numbers 19K08669), Miyagi Renal Association Research Grant, and the Koyanagi Foundation. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = jan,

doi = "10.3390/TOXINS13010050",

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AU - Kumakura, Satoshi

AU - Sato, Emiko

AU - Sekimoto, Akiyo

AU - Hashizume, Yamato

AU - Yamakage, Shu

AU - Miyazaki, Mariko

AU - Ito, Sadayoshi

AU - Harigae, Hideo

AU - Takahashi, Nobuyuki

N1 - Funding Information: Funding: This study was funded by JSPS KAKENHI (Grant Numbers 19K08669), Miyagi Renal Association Research Grant, and the Koyanagi Foundation. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/1

Y1 - 2021/1

N2 - 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.

AB - 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.

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KW - glycolysis

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

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Keywords

ASJC Scopus subject areas

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