TY - JOUR

T1 - Roles of NAD+ in Acute and Chronic Kidney Diseases

AU - Morevati, Marya

AU - Fang, Evandro Fei

AU - Mace, Maria L.

AU - Kanbay, Mehmet

AU - Gravesen, Eva

AU - Nordholm, Anders

AU - Egstrand, Søren

AU - Hornum, Mads

N1 - Publisher Copyright: © 2022 by the authors.

PY - 2023

Y1 - 2023

N2 - Nicotinamide adenine dinucleotide (oxidized form, NAD+) is a critical coenzyme, with functions ranging from redox reactions and energy metabolism in mitochondrial respiration and oxidative phosphorylation to being a central player in multiple cellular signaling pathways, organ resilience, health, and longevity. Many of its cellular functions are executed via serving as a co-substrate for sirtuins (SIRTs), poly (ADP-ribose) polymerases (PARPs), and CD38. Kidney damage and diseases are common in the general population, especially in elderly persons and diabetic patients. While NAD+ is reduced in acute kidney injury (AKI) and chronic kidney disease (CKD), mounting evidence indicates that NAD+ augmentation is beneficial to AKI, although conflicting results exist for cases of CKD. Here, we review recent progress in the field of NAD+, mainly focusing on compromised NAD+ levels in AKI and its effect on essential cellular pathways, such as mitochondrial dysfunction, compromised autophagy, and low expression of the aging biomarker αKlotho (Klotho) in the kidney. We also review the compromised NAD+ levels in renal fibrosis and senescence cells in the case of CKD. As there is an urgent need for more effective treatments for patients with injured kidneys, further studies on NAD+ in relation to AKI/CKD may shed light on novel therapeutics.

AB - Nicotinamide adenine dinucleotide (oxidized form, NAD+) is a critical coenzyme, with functions ranging from redox reactions and energy metabolism in mitochondrial respiration and oxidative phosphorylation to being a central player in multiple cellular signaling pathways, organ resilience, health, and longevity. Many of its cellular functions are executed via serving as a co-substrate for sirtuins (SIRTs), poly (ADP-ribose) polymerases (PARPs), and CD38. Kidney damage and diseases are common in the general population, especially in elderly persons and diabetic patients. While NAD+ is reduced in acute kidney injury (AKI) and chronic kidney disease (CKD), mounting evidence indicates that NAD+ augmentation is beneficial to AKI, although conflicting results exist for cases of CKD. Here, we review recent progress in the field of NAD+, mainly focusing on compromised NAD+ levels in AKI and its effect on essential cellular pathways, such as mitochondrial dysfunction, compromised autophagy, and low expression of the aging biomarker αKlotho (Klotho) in the kidney. We also review the compromised NAD+ levels in renal fibrosis and senescence cells in the case of CKD. As there is an urgent need for more effective treatments for patients with injured kidneys, further studies on NAD+ in relation to AKI/CKD may shed light on novel therapeutics.

KW - acute kidney injury

KW - autophagy

KW - chronic kidney disease

KW - fibrosis

KW - Klotho

KW - mitochondria

KW - NAD

KW - senescent

UR - http://www.scopus.com/inward/record.url?scp=85145978388&partnerID=8YFLogxK

U2 - 10.3390/ijms24010137

DO - 10.3390/ijms24010137

M3 - Review

C2 - 36613582

AN - SCOPUS:85145978388

VL - 24

JO - International Journal of Molecular Sciences (Online)

JF - International Journal of Molecular Sciences (Online)

SN - 1661-6596

IS - 1

M1 - 137

ER -