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Review
. 2022 May;42(3):151287.
doi: 10.1016/j.semnephrol.2022.10.013. Epub 2022 Nov 18.

The Significance of NAD+ Biosynthesis Alterations in Acute Kidney Injury

Amanda J Clark  1 , Marie Christelle Saade  2 , Samir M Parikh  3
Affiliations
Review

The Significance of NAD+ Biosynthesis Alterations in Acute Kidney Injury

Amanda J Clark et al. Semin Nephrol. 2022 May.

Abstract

Acute kidney injury (AKI) is a serious and highly prevalent disease, yet only supportive treatment is available. Nicotinamide adenine dinucleotide (NAD+) is a cofactor necessary for adenosine triphosphate (ATP) production and cell survival. Changes in renal NAD+ biosynthesis and energy utilization are features of AKI. Targeting NAD+ as an AKI therapy shows promising potential. However, the pursuit of NAD+-based treatments requires deeper understanding of the unique drivers and effects of the NAD+ biosynthesis derangements that arise in AKI. This article summarizes the NAD+ biosynthesis alterations in the kidney in AKI, chronic disease, and aging. To enhance this understanding, we explore instances of NAD+ biosynthesis alterations outside the kidney in inflammation, pregnancy, and cancer. In doing so, we seek to highlight that the different NAD+ biosynthesis pathways are not interconvertible and propose that the way in which NAD+ is synthesized may be just as important as the NAD+ produced.

Keywords: AKI; NAD+; NAD+ biosynthesis; cancer; metabolism; pregnancy.

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Conflict of interest statement

Samir M. Parikh has received consulting fees from Janssen, Pfizer, Mission Therapeutics, Flagship Pioneering, Astellas, Merck, Boehringer Ingelheim, Astra Zeneca, Casma Therapeutics, and Entrada Therapeutics, and is on the scientific advisory boards of Cytokinetics, Mission Therapeutics, and NovMetaPharma.

Figures

Figure 1.
Figure 1.
Pathways of nicotinamide adenine dinucleotide (NAD+) biosynthesis. Dotted lines represent theoretical pathways. Abbreviations: AFMID, arylformamidase; IDO, indoleamine 2,3-dioxygenase; KMO, kynurenine 3-monooxygenase; KYNU, kynureninase; NAAD, nicotinic acid adenine dinucleotide; NADSYN, nicotinamide adenine dinucleotide synthetase; NAMN, nicotinic acid mononucleotide; NAMPT, nicotinamide phosphoribostransferase; NAPRT, nicotinate phosphoribosyltransferase; NMN, nicotinamide mononucleotide; NMNAT, nicotinamide nucleotide adenylyltansferase; NRK1,2, nicotinamide riboside kinase 1,2; PNP, purine-nucleoside phosphorylase; QPRT, quinolinic acid phosphoribosyltransferase; TDO, tryptophan-2,3-dioxygenase; 3HAO, 3, hydroxyanthranilate 3,4 dioxygenase.
Figure 2.
Figure 2.
Different organs use different sources to synthesize nicotinamide adenine dinucleotide (NAD+). Abbreviations: NA, nicotinic acid; NAM, nicotinamide.
Figure 3.
Figure 3.
Targeted accumulation of de novo nicotinamide adenine dinucleotide (NAD+) biosynthesis metabolites. Abbreviations: AFMID, arylformamidase; IDO, indoleamine 2,3-dioxygenase; KMO, kynurenine 3-monooxygenase; KYNU, kynureninase; QPRT, quinolinic acid phosphoribosyltransferase; TDO, tryptophan-2,3-dioxygenase; 3HAO, 3, hydroxyanthranilate 3,4 dioxygenase.
See this image and copyright information in PMC

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