PMID- 34043214
OWN - NLM
STAT- MEDLINE
DCOM- 20220217
LR  - 20220218
IS  - 1720-8386 (Electronic)
IS  - 0391-4097 (Print)
IS  - 0391-4097 (Linking)
VI  - 44
IP  - 12
DP  - 2021 Dec
TI  - Urinary complement proteins and risk of end-stage renal disease: quantitative 
      urinary proteomics in patients with type 2 diabetes and biopsy-proven diabetic 
      nephropathy.
PG  - 2709-2723
LID - 10.1007/s40618-021-01596-3 [doi]
AB  - PURPOSE: To investigate the association between urinary complement proteins and 
      renal outcome in biopsy-proven diabetic nephropathy (DN). METHODS: Untargeted 
      proteomic and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses 
      and targeted proteomic analysis using parallel reaction-monitoring (PRM)-mass 
      spectrometry was performed to determine the abundance of urinary complement 
      proteins in healthy controls, type 2 diabetes mellitus (T2DM) patients, and 
      patients with T2DM and biopsy-proven DN. The abundance of each urinary complement 
      protein was individually included in Cox proportional hazards models for 
      predicting progression to end-stage renal disease (ESRD). RESULTS: Untargeted 
      proteomic and functional analysis using the KEGG showed that differentially 
      expressed urinary proteins were primarily associated with the complement and 
      coagulation cascades. Subsequent urinary complement proteins quantification using 
      PRM showed that urinary abundances of C3, C9, and complement factor H (CFAH) 
      correlated negatively with annual estimated glomerular filtration rate (eGFR) 
      decline, while urinary abundances of C5, decay-accelerating factor (DAF), and 
      CD59 correlated positively with annual rate of eGFR decline. Furthermore, higher 
      urinary abundance of CFAH and lower urinary abundance of DAF were independently 
      associated with greater risk of progression to ESRD. Urinary abundance of CFAH 
      and DAF had a larger area under the curve (AUC) than that of eGFR, proteinuria, 
      or any pathological parameter. Moreover, the model that included CFAH or DAF had 
      a larger AUC than that with only clinical or pathological parameters. CONCLUSION: 
      Urinary abundance of complement proteins was significantly associated with ESRD 
      in patients with T2DM and biopsy-proven DN, indicating that therapeutically 
      targeting the complement pathway may alleviate progression of DN.
CI  - (c) 2021. The Author(s).
FAU - Zhao, L
AU  - Zhao L
AD  - Division of Nephrology, Laboratory of Diabetic Kidney Disease, Centre of Diabetes 
      and Metabolism Research, West China Hospital of Sichuan University, No. 37, 
      Guoxue Alley, Chengdu, 610041, Sichuan Province, China.
AD  - Division of General Practice, West China Hospital of Sichuan University, Chengdu, 
      Sichuan, China.
AD  - Laboratory of Diabetic Kidney Disease, Centre of Diabetes and Metabolism 
      Research, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
FAU - Zhang, Y
AU  - Zhang Y
AD  - Key Laboratory of Transplant Engineering and Immunology, MOH, West China Hospital 
      of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan Province, 
      China.
AD  - West China-Washington Mitochondria and Metabolism Research Center, West China 
      Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan 
      Province, China.
AD  - Frontiers Science Center for Disease-Related Molecular Network, West China 
      Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan 
      Province, China.
FAU - Liu, F
AU  - Liu F
AUID- ORCID: 0000-0003-1121-3004
AD  - Division of Nephrology, Laboratory of Diabetic Kidney Disease, Centre of Diabetes 
      and Metabolism Research, West China Hospital of Sichuan University, No. 37, 
      Guoxue Alley, Chengdu, 610041, Sichuan Province, China. liufangfh@163.com.
AD  - Division of General Practice, West China Hospital of Sichuan University, Chengdu, 
      Sichuan, China. liufangfh@163.com.
AD  - Laboratory of Diabetic Kidney Disease, Centre of Diabetes and Metabolism 
      Research, West China Hospital of Sichuan University, Chengdu, Sichuan, China. 
      liufangfh@163.com.
FAU - Yang, H
AU  - Yang H
AD  - Key Laboratory of Transplant Engineering and Immunology, MOH, West China Hospital 
      of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan Province, 
      China. yanghao@scu.edu.cn.
AD  - West China-Washington Mitochondria and Metabolism Research Center, West China 
      Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan 
      Province, China. yanghao@scu.edu.cn.
AD  - Frontiers Science Center for Disease-Related Molecular Network, West China 
      Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan 
      Province, China. yanghao@scu.edu.cn.
FAU - Zhong, Y
AU  - Zhong Y
AD  - Key Laboratory of Transplant Engineering and Immunology, MOH, West China Hospital 
      of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan Province, 
      China.
AD  - West China-Washington Mitochondria and Metabolism Research Center, West China 
      Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan 
      Province, China.
AD  - Frontiers Science Center for Disease-Related Molecular Network, West China 
      Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan 
      Province, China.
FAU - Wang, Y
AU  - Wang Y
AD  - Division of Nephrology, Laboratory of Diabetic Kidney Disease, Centre of Diabetes 
      and Metabolism Research, West China Hospital of Sichuan University, No. 37, 
      Guoxue Alley, Chengdu, 610041, Sichuan Province, China.
AD  - Division of General Practice, West China Hospital of Sichuan University, Chengdu, 
      Sichuan, China.
FAU - Li, S
AU  - Li S
AD  - Division of General Practice, West China Hospital of Sichuan University, Chengdu, 
      Sichuan, China.
FAU - Su, Q
AU  - Su Q
AD  - Division of General Practice, West China Hospital of Sichuan University, Chengdu, 
      Sichuan, China.
FAU - Tang, L
AU  - Tang L
AD  - Histology and Imaging Platform, Core Facility of West China Hospital, Chengdu, 
      Sichuan, China.
FAU - Bai, L
AU  - Bai L
AD  - Histology and Imaging Platform, Core Facility of West China Hospital, Chengdu, 
      Sichuan, China.
FAU - Ren, H
AU  - Ren H
AD  - Division of Nephrology, Laboratory of Diabetic Kidney Disease, Centre of Diabetes 
      and Metabolism Research, West China Hospital of Sichuan University, No. 37, 
      Guoxue Alley, Chengdu, 610041, Sichuan Province, China.
AD  - Division of General Practice, West China Hospital of Sichuan University, Chengdu, 
      Sichuan, China.
FAU - Zou, Y
AU  - Zou Y
AD  - Division of Nephrology, Laboratory of Diabetic Kidney Disease, Centre of Diabetes 
      and Metabolism Research, West China Hospital of Sichuan University, No. 37, 
      Guoxue Alley, Chengdu, 610041, Sichuan Province, China.
AD  - Division of General Practice, West China Hospital of Sichuan University, Chengdu, 
      Sichuan, China.
FAU - Wang, S
AU  - Wang S
AD  - Key Laboratory of Transplant Engineering and Immunology, MOH, West China Hospital 
      of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan Province, 
      China.
AD  - West China-Washington Mitochondria and Metabolism Research Center, West China 
      Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan 
      Province, China.
AD  - Frontiers Science Center for Disease-Related Molecular Network, West China 
      Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan 
      Province, China.
FAU - Zheng, S
AU  - Zheng S
AD  - Key Laboratory of Transplant Engineering and Immunology, MOH, West China Hospital 
      of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan Province, 
      China.
AD  - West China-Washington Mitochondria and Metabolism Research Center, West China 
      Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan 
      Province, China.
AD  - Frontiers Science Center for Disease-Related Molecular Network, West China 
      Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan 
      Province, China.
FAU - Xu, H
AU  - Xu H
AD  - Division of Pathology, West China Hospital of Sichuan University, Chengdu, 
      Sichuan, China.
FAU - Li, L
AU  - Li L
AD  - Division of Pathology, West China Hospital of Sichuan University, Chengdu, 
      Sichuan, China.
FAU - Zhang, J
AU  - Zhang J
AD  - Histology and Imaging Platform, Core Facility of West China Hospital, Chengdu, 
      Sichuan, China.
FAU - Chai, Z
AU  - Chai Z
AD  - Department of Diabetes, Central Clinical School, Monash University, Melbourne, 
      Australia.
FAU - Cooper, M E
AU  - Cooper ME
AD  - Department of Diabetes, Central Clinical School, Monash University, Melbourne, 
      Australia.
FAU - Tong, N
AU  - Tong N
AD  - Division of Endocrinology, West China Hospital of Sichuan University, Chengdu, 
      Sichuan, China.
LA  - eng
GR  - 81970626/National Natural Science Foundation of China/
GR  - 19ZDYF1273/Key Research and Development Project of Sichuan Science Technology 
      Department/
GR  - 19PJ250/Popularization Project of the Science and Technology Project of the 
      Sichuan Health Planning Committee under Grant/
PT  - Journal Article
DEP - 20210527
PL  - Italy
TA  - J Endocrinol Invest
JT  - Journal of endocrinological investigation
JID - 7806594
RN  - 9007-36-7 (Complement System Proteins)
SB  - IM
MH  - Biopsy/methods
MH  - *Complement System Proteins/metabolism/urine
MH  - Correlation of Data
MH  - Diabetes Mellitus, Type 2/*complications
MH  - *Diabetic Nephropathies/etiology/metabolism/physiopathology
MH  - Disease Progression
MH  - Drug Discovery
MH  - Female
MH  - Humans
MH  - Kidney/*pathology
MH  - *Kidney Failure, Chronic/diagnosis/metabolism/prevention & control
MH  - Kidney Function Tests/methods
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Proteinuria/diagnosis/etiology
MH  - Proteomics/methods
MH  - Signal Transduction/drug effects
PMC - PMC8572220
OTO - NOTNLM
OT  - Complement
OT  - Diabetic nephropathy
OT  - End-stage renal disease
OT  - Urinary proteomics
COIS- The authors declare that they do not have conflicts of interest.
EDAT- 2021/05/28 06:00
MHDA- 2022/02/19 06:00
PMCR- 2021/05/27
CRDT- 2021/05/27 12:41
PHST- 2021/01/27 00:00 [received]
PHST- 2021/05/18 00:00 [accepted]
PHST- 2021/05/28 06:00 [pubmed]
PHST- 2022/02/19 06:00 [medline]
PHST- 2021/05/27 12:41 [entrez]
PHST- 2021/05/27 00:00 [pmc-release]
AID - 10.1007/s40618-021-01596-3 [pii]
AID - 1596 [pii]
AID - 10.1007/s40618-021-01596-3 [doi]
PST - ppublish
SO  - J Endocrinol Invest. 2021 Dec;44(12):2709-2723. doi: 10.1007/s40618-021-01596-3. 
      Epub 2021 May 27.