Titre
Differential role of nicotinamide adenine dinucleotide deficiency in acute and chronic kidney disease.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Faivre, A.
Auteure/Auteur
Katsyuba, E.
Auteure/Auteur
Verissimo, T.
Auteure/Auteur
Lindenmeyer, M.
Auteure/Auteur
Rajaram, R.D.
Auteure/Auteur
Naesens, M.
Auteure/Auteur
Heckenmeyer, C.
Auteure/Auteur
Mottis, A.
Auteure/Auteur
Feraille, E.
Auteure/Auteur
Cippà, P.
Auteure/Auteur
Cohen, C.
Auteure/Auteur
Longchamp, A.
Auteure/Auteur
Allagnat, F.
Auteure/Auteur
Rutkowski, J.M.
Auteure/Auteur
Legouis, D.
Auteure/Auteur
Auwerx, J.
Auteure/Auteur
de Seigneux, S.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1460-2385
Statut éditorial
Publié
Date de publication
2021-01-01
Volume
36
Numéro
1
Première page
60
Dernière page/numéro d’article
68
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Nicotinamide adenine dinucleotide (NAD+) is a ubiquitous coenzyme involved in electron transport and a co-substrate for sirtuin function. NAD+ deficiency has been demonstrated in the context of acute kidney injury (AKI).
We studied the expression of key NAD+ biosynthesis enzymes in kidney biopsies from human allograft patients and patients with chronic kidney disease (CKD) at different stages. We used ischaemia-reperfusion injury (IRI) and cisplatin injection to model AKI, urinary tract obstruction [unilateral ureteral obstruction (UUO)] and tubulointerstitial fibrosis induced by proteinuria to investigate CKD in mice. We assessed the effect of nicotinamide riboside (NR) supplementation on AKI and CKD in animal models.
RNA sequencing analysis of human kidney allograft biopsies during the reperfusion phase showed that the NAD+de novo synthesis is impaired in the immediate post-transplantation period, whereas the salvage pathway is stimulated. This decrease in de novo NAD+ synthesis was confirmed in two mouse models of IRI where NR supplementation prevented plasma urea and creatinine elevation and tubular injury. In human biopsies from CKD patients, the NAD+de novo synthesis pathway was impaired according to CKD stage, with better preservation of the salvage pathway. Similar alterations in gene expression were observed in mice with UUO or chronic proteinuric glomerular disease. NR supplementation did not prevent CKD progression, in contrast to its efficacy in AKI.
Impairment of NAD+ synthesis is a hallmark of AKI and CKD. NR supplementation is beneficial in ischaemic AKI but not in CKD models.
We studied the expression of key NAD+ biosynthesis enzymes in kidney biopsies from human allograft patients and patients with chronic kidney disease (CKD) at different stages. We used ischaemia-reperfusion injury (IRI) and cisplatin injection to model AKI, urinary tract obstruction [unilateral ureteral obstruction (UUO)] and tubulointerstitial fibrosis induced by proteinuria to investigate CKD in mice. We assessed the effect of nicotinamide riboside (NR) supplementation on AKI and CKD in animal models.
RNA sequencing analysis of human kidney allograft biopsies during the reperfusion phase showed that the NAD+de novo synthesis is impaired in the immediate post-transplantation period, whereas the salvage pathway is stimulated. This decrease in de novo NAD+ synthesis was confirmed in two mouse models of IRI where NR supplementation prevented plasma urea and creatinine elevation and tubular injury. In human biopsies from CKD patients, the NAD+de novo synthesis pathway was impaired according to CKD stage, with better preservation of the salvage pathway. Similar alterations in gene expression were observed in mice with UUO or chronic proteinuric glomerular disease. NR supplementation did not prevent CKD progression, in contrast to its efficacy in AKI.
Impairment of NAD+ synthesis is a hallmark of AKI and CKD. NR supplementation is beneficial in ischaemic AKI but not in CKD models.
Sujets
PID Serval
serval:BIB_73C83D588458
PMID
Open Access
Oui
Date de création
2020-11-02T12:01:03.095Z
Date de création dans IRIS
2025-05-20T22:27:15Z