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      Analysis of the differential urinary protein profile in IgA nephropathy patients of Uygur ethnicity

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          Abstract

          Background

          IgA nephropathy (IgAN) is one of the most common forms of idiopathic glomerular diseases and might lead to end-stage kidney disease. Accurate and non-invasive biomarkers for early diagnosis are required for early intervention and consequent therapy for IgAN patients. Because variance in the disease incidence and predisposing genes of IgAN has been detected among different ethnicities, the ethnicity factor should be considered in IgAN biomarker discovery. The differences in the protein profiles and pathological mechanisms of IgAN in patients of Uygur ethnicity need to be clearly illustrated.

          Methods

          In this study, we used urinary proteomics to discover candidate biomarkers of IgAN in patients of Uygur ethnicity. The urinary proteins from Uygur normal control and Uygur IgAN patients were extracted and analyzed using 2D-LC-MS/MS and isobaric tags for relative and absolute quantitation (iTRAQ) analysis.

          Results

          A total of 277 proteins were found to be differentially represented in Uygur IgAN compared with the respective normal controls. The bioinformatics analysis revealed that the immune response, cell survival, and complement system were activated in Uygur IgAN. Many differentially expressed proteins were found to be related to nephropathy and kidney injuries. Four candidate biomarkers were validated by Western blot, and these results were consistent with the iTRAQ results. ICAM1, TIMP1, SERPINC1 and ADIPOQ were upregulated in Uygur IgAN. Bioinformatic analysis revealed that the increase of ICAM1 and TIMP1 might be caused by IgAN, but the increase of SERPINC1 and ADIPOQ might be caused by proteinuria. SERPINC1 and ICAM1 were identified as the candidate biomarkers with excellent area-under-the-curve (AUC) values (0.84) for distinguishing Uygur IgAN from normal controls.

          Conclusions

          Using urinary proteomic analysis, we identified several candidate biomarkers for IgAN in patients of Uygur ethnicity. These results will prove helpful for exploring the pathological mechanism of IgAN in patients of Uygur ethnicity and for developing better treatments for these patients.

          Electronic supplementary material

          The online version of this article (10.1186/s12882-018-1139-3) contains supplementary material, which is available to authorized users.

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          Most cited references35

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          IgA nephropathy.

          James Donadio, Joseph Grande (2002)
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            Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy.

            Hyeong-Gon Moon, Jeong Lee, Kee Kwon … (2011)
            To identify biomarker candidates associated with early IgA nephropathy (IgAN) and thin basement membrane nephropathy (TBMN), the most common causes presenting isolated hematuria in childhood, a proteomic approach of urinary exosomes from early IgAN and TBMN patients was introduced. The proteomic results from the patients were compared with a normal group to understand the pathophysiological processes associated with these diseases at the protein level. The urinary exosomes, which reflect pathophysiological processes, collected from three groups of young adults (early IgAN, TBMN, and normal) were trypsin-digested using a gel-assisted protocol, and quantified by label-free LC-MS/MS, using an MS(E) mode. A total of 1877 urinary exosome proteins, including cytoplasmic, membrane, and vesicle trafficking proteins, were identified. Among the differentially expressed proteins, four proteins (aminopeptidase N, vasorin precursor, α-1-antitrypsin, and ceruloplasmin) were selected as biomarker candidates to differentiate early IgAN from TBMN. We confirmed the protein levels of the four biomarker candidates by semi-quantitative immunoblot analysis in urinary exosomes independently prepared from other patients, including older adult groups. Further clinical studies are needed to investigate the diagnostic and prognostic value of these urinary markers for early IgAN and TBMN. Taken together, this study showed the possibility of identifying biomarker candidates for human urinary diseases using urinary exosomes and might help to understand the pathophysiology of early IgAN and TBMN at the protein level. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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              The changing spectrum of primary glomerular diseases within 15 years: a survey of 3331 patients in a single Chinese centre.

              Ming-Hui Zhao, Zhong Zou, Fu-Fu Zhou … (2009)
              Primary glomerular disease (PGD) is the leading cause of end-stage renal disease (ESRD) in China. With the development of socioeconomic status of Chinese people in the last two decades, PGD in ESRD is intent to decrease. However, whether this affects the spectrum of PGD is not clear. The aim of the current study is to investigate the changing spectrum of PGD in China. The records of 5398 consecutive native renal biopsies performed in adults (>or=14 years of age) in our centre between 1993 and 2007 were retrospectively analysed. The criteria for renal biopsy and pathologic diagnosis were kept unchanged. The patients were grouped according to a 5-year interval, 1993-97 (period 1), 1998-2002 (period 2) and 2003-07 (period 3). Then they were divided into four groups according to age for stratified analysis: 14-24 years, 25-44 years, 45-59 years and the elderly (>or=60 years). Three thousand, three hundred and thirty-one patients were diagnosed with PGD. PGD remained the most common renal disease, accounting for 65.9%, 57.7% and 63.2% in period 1, 2 and 3, respectively, without any significant difference. The proportion of elder patients increased significantly from 0% in 1993 to 9.1% in 2007 (P < 0.001). Within 1993-97, the leading PGD was IgA nephropathy (50.7%), followed by non-IgA MsPGN (19.9%), membranous nephropathy (MN) (13.3%) and minimal change disease (MCD) (6.3%), while within 2003-07, the most common PGD was still IgAN (58.2%), but followed by MN (14.3%), MCD (13.4%) and non-IgA MsPGN (7.0%). The age-adjusted frequency of IgAN and MCD increased significantly from period 1 to period 3 (P < 0.01 and P < 0.001, respectively), while that of non-IgA MsPGN, EnPGN and MPGN decreased significantly (P < 0.001, P < 0.01 and P < 0.05, respectively). There was no significant change in the age-adjusted frequency of FSGS, MN and CreGN during the study period. However, when patients were stratified by age, a sixfold increase in frequency of FSGS was identified in the 14- to 24-year group (P < 0.01). The spectrum of primary glomerulonephritis has changed within the last 15 years. The relative frequency of non-IgA MsPGN, EnPGN and MPGN decreased significantly, while that of MCD and IgA nephropathy increased significantly. The relative frequency of FSGS increased significantly in younger patients.
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                Author and article information

                Contributors
                Zhengguang Guo: gzg0625@sina.com
                Zhao Wang: wangzhao_0508@163.com
                Chen Lu: luchen706@163.com
                Shufen Yang: ysfzhl5115@163.com
                Haidan Sun: sunhd15@163.com
                Reziw: reziw0128@163.com
                Yu Guo: 15199146962@163.com
                Wei Sun: sunwei1018@hotmail.com
                Hua Yue: yuehua3546@126.com
                Journal
                Journal ID (nlm-ta): BMC Nephrol
                Journal ID (iso-abbrev): BMC Nephrol
                Title: BMC Nephrology
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1471-2369
                Publication date (Electronic): 14 December 2018
                Publication date PMC-release: 14 December 2018
                Publication date Collection: 2018
                Volume: 19
                Electronic Location Identifier: 358
                Affiliations
                [1 ]ISNI 0000 0001 0662 3178, GRID grid.12527.33, Core Facility of Instrument, Institute of Basic Medicine, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, ; 5 Dong Dan San Tiao, Beijing, China
                [2 ]Nephrology department, The Xinjiang Uygur Autonomous Region People’s Hospital, 91 Tianchi Road, Urumqi, Xinjiang China
                [3 ]ISNI 0000 0004 1799 3993, GRID grid.13394.3c, Graduate School, Xinjiang Medical University, ; 393 Xinyi Road, Urumqi, Xinjiang China
                Article
                Publisher ID: 1139
                DOI: 10.1186/s12882-018-1139-3
                PMC ID: 6295011
                PubMed ID: 30547763
                SO-VID: 07f79606-4583-45da-8c36-16c90d295f10
                Copyright © © The Author(s). 2018
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 1 October 2017
                Date accepted : 15 November 2018
                Funding
                Funded by: National Natural Science Foundation of China (CN)
                Award ID: 30970650
                Award ID: 31200614
                Award ID: 81371515
                Award Recipient :
                Funded by: National Basic Research Program of China
                Award ID: 2013CB530805
                Award ID: 2014CBA02005
                Award Recipient :
                Funded by: Key Basic Research Program of the Ministry of Science and Technology of China
                Award ID: 2013FY114100
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 31400669
                Award ID: 81170665
                Award Recipient :
                Funded by: National Natural Science Foundation of China
                Award ID: 81560121
                Award Recipient :
                Funded by: The Science and Technology Yuanjiang Project of Xinjiang Uygur Autonomous Region
                Award ID: 2013911114
                Award Recipient :
                Funded by: National Key Research and Development Program of China
                Award ID: 2016 YFC 1306300
                Award Recipient :
                Funded by: CAMS Innovation Fund for Medical Sciences
                Award ID: 2017-I2M-1-009
                Award Recipient :
                Funded by: CAMS special basic research fund for central public research institutes
                Award ID: 2017PT310004
                Award Recipient :
                Categories
                Subject: Research Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2018

                ScienceOpen disciplines: Nephrology
                Keywords: iga nephropathy,urinary proteomics,uygur,biomarker
                Data availability:
                ScienceOpen disciplines: Nephrology
                Keywords: iga nephropathy, urinary proteomics, uygur, biomarker

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