PMID- 36275902
OWN - NLM
STAT- MEDLINE
DCOM- 20221025
LR  - 20221025
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2022
DP  - 2022
TI  - Glutathione Peroxidase 4 Is a Predictor of Diabetic Kidney Disease Progression in 
      Type 2 Diabetes Mellitus.
PG  - 2948248
LID - 10.1155/2022/2948248 [doi]
LID - 2948248
AB  - BACKGROUND: Diabetic kidney disease (DKD) represents a heavy burden in type 2 
      diabetes mellitus (T2DM). Ferroptosis plays an important role in DKD, and it thus 
      provides new perspectives to pursue more related biomarkers to assess the disease 
      severity and prognosis. Glutathione peroxidase 4 (GPX4) is the mainstay in 
      regulating ferroptosis. The current study investigated the predictive value of 
      kidney GPX4 expression level in DKD progression. METHODS: We measured GPX4 levels 
      in kidney paraffin sections of 85 biopsy-proven DKD patients by 
      immunohistochemistry staining. The associations between the GPX4 level and 
      clinicopathological parameters as well as renal outcomes were analyzed. RESULTS: 
      GPX4 is mainly expressed in kidney tubulointerstitium, especially in tubular 
      epithelial cells of DKD patients. The GPX4 expression level was significantly 
      lower in DKD patients than healthy controls. Besides, GPX4 level significantly 
      correlated with proteinuria (r = -0.42, p < 0.001), urinary albumin-to-creatinine 
      ratio (uACR) (r = -0.40, p < 0.01), serum creatinine (Scr) (r = -0.59, p < 
      0.001), estimated glomerular filtration rate (eGFR) (r = 0.66, p < 0.001), and 
      the percentage of sclerosed glomeruli (r = -0.42, p < 0.001) in renal specimens. 
      During follow-up, the GPX4 level positively correlated with eGFR slope (r = 0.48, 
      p < 0.001), and GPX4-low patients showed a significantly higher probability of 
      developing end-stage kidney disease (ESKD) compared with GPX4-high patients (p < 
      0.01). Moreover, after adjusting for other potential predictors, the GPX4 level 
      was still an independent predictor of developing ESKD (HR 2.15, 95% CI 1.08 to 
      4.28, p < 0.05). CONCLUSIONS: Kidney tubulointerstitial GPX4 expression level was 
      associated with the disease severity and progression of DKD.
CI  - Copyright (c) 2022 Yi-hui Wang et al.
FAU - Wang, Yi-Hui
AU  - Wang YH
AUID- ORCID: 0000-0002-8511-3017
AD  - Renal Division, Department of Medicine, Peking University First Hospital, 
      Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, 
      Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention 
      and Treatment (Peking University), Ministry of Education, Beijing 100034, China.
AD  - Peking-Tsinghua Center for Life Sciences, Beijing, China.
FAU - Chang, Dong-Yuan
AU  - Chang DY
AUID- ORCID: 0000-0002-3696-5993
AD  - Renal Division, Department of Medicine, Peking University First Hospital, 
      Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, 
      Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention 
      and Treatment (Peking University), Ministry of Education, Beijing 100034, China.
AD  - Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, 
      Chinese Academy of Medical Sciences, Beijing, China.
FAU - Zhao, Ming-Hui
AU  - Zhao MH
AUID- ORCID: 0000-0003-3340-3108
AD  - Renal Division, Department of Medicine, Peking University First Hospital, 
      Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, 
      Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention 
      and Treatment (Peking University), Ministry of Education, Beijing 100034, China.
AD  - Peking-Tsinghua Center for Life Sciences, Beijing, China.
AD  - Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, 
      Chinese Academy of Medical Sciences, Beijing, China.
FAU - Chen, Min
AU  - Chen M
AUID- ORCID: 0000-0002-6413-6973
AD  - Renal Division, Department of Medicine, Peking University First Hospital, 
      Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, 
      Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention 
      and Treatment (Peking University), Ministry of Education, Beijing 100034, China.
AD  - Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, 
      Chinese Academy of Medical Sciences, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20221012
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - AYI8EX34EU (Creatinine)
RN  - EC 1.11.1.12 (Phospholipid Hydroperoxide Glutathione Peroxidase)
RN  - 8002-74-2 (Paraffin)
RN  - 0 (Biomarkers)
RN  - 0 (Albumins)
SB  - IM
MH  - Humans
MH  - *Diabetic Nephropathies/metabolism
MH  - Creatinine/urine
MH  - *Diabetes Mellitus, Type 2/complications
MH  - Phospholipid Hydroperoxide Glutathione Peroxidase
MH  - Paraffin
MH  - Glomerular Filtration Rate
MH  - Biomarkers
MH  - *Kidney Failure, Chronic/complications
MH  - Albumins
MH  - Disease Progression
PMC - PMC9581693
COIS- All the authors declared no competing interests.
EDAT- 2022/10/25 06:00
MHDA- 2022/10/26 06:00
PMCR- 2022/10/12
CRDT- 2022/10/24 04:07
PHST- 2022/02/09 00:00 [received]
PHST- 2022/08/18 00:00 [revised]
PHST- 2022/09/09 00:00 [accepted]
PHST- 2022/10/24 04:07 [entrez]
PHST- 2022/10/25 06:00 [pubmed]
PHST- 2022/10/26 06:00 [medline]
PHST- 2022/10/12 00:00 [pmc-release]
AID - 10.1155/2022/2948248 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2022 Oct 12;2022:2948248. doi: 10.1155/2022/2948248. 
      eCollection 2022.