PMID- 33547785
OWN - NLM
STAT- MEDLINE
DCOM- 20220426
LR  - 20220602
IS  - 1460-2385 (Electronic)
IS  - 0931-0509 (Linking)
VI  - 37
IP  - 5
DP  - 2022 Apr 25
TI  - Systematic review of the nuclear factor erythroid 2-related factor 2 (NRF2) 
      system in human chronic kidney disease: alterations, interventions and relation 
      to morbidity.
PG  - 904-916
LID - 10.1093/ndt/gfab031 [doi]
AB  - BACKGROUND: Nuclear factor erythroid 2-related factor 2 (NRF2) and its effectors 
      NAD(P)H:quinoneoxidoreductase 1 (NQO1) and haem oxygenase 1 (HO-1) are of 
      interest in kidney disease. We therefore reviewed studies about their status in 
      patients with chronic kidney disease (CKD). METHODS: We undertook systematic 
      searches of PubMed and Excerpta Medica dataBASE (EMBASE) databases. Alterations 
      of NRF2, NQO1 and HO-1 in CKD, their responses to interventions and their 
      relation to clinically relevant parameters were reported. RESULTS: We identified 
      1373 articles, of which 32 studies met the inclusion criteria. NRF2 levels were 
      decreased in the majority of analyses of CKD patients. Half of the analyses 
      showed a similar or increased NQO1 level versus control, whereas in half of the 
      analyses NQO1 was decreased. Most of the studies reported either an increased or 
      similar HO-1 level in CKD patients compared with controls. For patients with CKD 
      Stages 1-4, studies reported positive correlations to markers of kidney disease 
      severity. Also, positive associations of NQO1/HO-1 levels to inflammation and 
      comorbidities were reported. One-third of the studies showed discordant changes 
      between gene expression and protein level of NRF2 system components. Two-thirds 
      of intervention studies (50% dietary, such as using resistant starch) reported an 
      increase of NRF2, NQO1 or HO-1. CONCLUSIONS: In patients with CKD, NRF2 
      expression was downregulated, while NQO1 and HO-1 showed varying alterations 
      related to inflammation, comorbidities and severity of kidney damage. 
      Interventions that increased NRF2 system components were described, but their 
      effectiveness and clinical relevance require further clinical studies of high 
      quality. Research on gene expression together with protein analyses is 
      indispensable to understand NRF2 system alterations in CKD.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the 
      ERA-EDTA.
FAU - Juul-Nielsen, Christoffer
AU  - Juul-Nielsen C
AD  - Department of Nephrology, Odense University Hospital, Odense, Denmark.
FAU - Shen, Jianlin
AU  - Shen J
AD  - Department of Orthopedics, The Third Affiliated Hospital of Southern Medical 
      University, Guangzhou, PR China.
FAU - Stenvinkel, Peter
AU  - Stenvinkel P
AD  - Department of Renal Medicine, Karolinska University Hospital at Huddinge, 
      Karolinska Institutet, Stockholm, Sweden.
FAU - Scholze, Alexandra
AU  - Scholze A
AUID- ORCID: 0000-0002-3100-8692
AD  - Department of Nephrology, Odense University Hospital, Odense, Denmark.
AD  - Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (NF-E2-Related Factor 2)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
SB  - IM
MH  - Female
MH  - Heme Oxygenase-1/genetics/metabolism
MH  - Humans
MH  - Inflammation
MH  - Male
MH  - Morbidity
MH  - *NF-E2-Related Factor 2/genetics/metabolism
MH  - Oxidative Stress
MH  - *Renal Insufficiency, Chronic
OTO - NOTNLM
OT  - CKD
OT  - HO-1
OT  - NQO1
OT  - NRF2
OT  - oxidative stress
EDAT- 2021/02/07 06:00
MHDA- 2022/04/27 06:00
CRDT- 2021/02/06 08:33
PHST- 2020/12/15 00:00 [received]
PHST- 2021/02/07 06:00 [pubmed]
PHST- 2022/04/27 06:00 [medline]
PHST- 2021/02/06 08:33 [entrez]
AID - 6129762 [pii]
AID - 10.1093/ndt/gfab031 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2022 Apr 25;37(5):904-916. doi: 10.1093/ndt/gfab031.