Open AccessEffect of NAD+ boosting on kidney ischemia-reperfusion injury
Author(s) -
Marya Morevati,
Søren Egstrand,
Anders Nordholm,
Maria L Mace,
Claus B Andersen,
Rouzbeh Salmani,
Klaus Ølgaard,
Ewa Lewin
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0252554
Subject(s) - nad+ kinase , autophagy , nicotinamide adenine dinucleotide , kidney disease , medicine , kidney , endocrinology , acute kidney injury , fibrosis , ischemia , sirt3 , sirtuin 1 , sirtuin , nicotinamide phosphoribosyltransferase , reperfusion injury , nicotinamide adenine dinucleotide phosphate , pharmacology , chemistry , biochemistry , enzyme , downregulation and upregulation , oxidase test , apoptosis , gene
Acute kidney injury (AKI) is associated with a very high mortality and an increased risk for progression to chronic kidney disease (CKD). Ischemia-reperfusion injury (IRI) is a model for AKI, which results in tubular damage, dysfunction of the mitochondria and autophagy, and in decreased cellular nicotinamide adenine dinucleotide (NAD + ) with progressing fibrosis resulting in CKD. NAD + is a co-enzyme for several proteins, including the NAD + dependent sirtuins. NAD + augmentation, e.g. by use of its precursor nicotinamide riboside (NR), improves mitochondrial homeostasis and organismal metabolism in many species. In the present investigation the effects of prophylactic administration of NR on IRI-induced AKI were studied in the rat. Bilateral IRI reduced kidney tissue NAD + , caused tubular damage, reduced α-Klotho (klotho), and altered autophagy flux. AKI initiated progression to CKD, as shown by induced profibrotic Periostin ( postn ) and Inhibin subunit beta-A, ( activin A / Inhba ), both 24 hours and 14 days after surgery. NR restored tissue NAD + to that of the sham group, increased autophagy (reduced p62) and sirtuin1 ( Sirt1 ) but did not ameliorate renal tubular damage and profibrotic genes in the 24 hours and 14 days IRI models. AKI induced NAD + depletion and impaired autophagy, while augmentation of NAD + by NR restored tissue NAD + and increased autophagy, possibly serving as a protective response. However, prophylactic administration of NR did not ameliorate tubular damage of the IRI rats nor rescued the initiation of fibrosis in the long-term AKI to CKD model, which is a pivotal event in CKD pathogenesis.