Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes
Abstract Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabet...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-83856-z |
| _version_ | 1831706086342656000 |
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| author | Lijun Zhao Fang Liu Lin Li Junlin Zhang Tingli Wang Rui Zhang Wei Zhang Xiaoyan Yang Xiaoxi Zeng Yiting Wang Yucheng Wu Hao Yang Shisheng Wang Yi Zhong Huan Xu Shanshan Wang Ruikun Guo Honghong Ren Lichuan Yang Baihai Su Jie Zhang Nanwei Tong Xin J. Zhou Mark E. Cooper |
| author_facet | Lijun Zhao Fang Liu Lin Li Junlin Zhang Tingli Wang Rui Zhang Wei Zhang Xiaoyan Yang Xiaoxi Zeng Yiting Wang Yucheng Wu Hao Yang Shisheng Wang Yi Zhong Huan Xu Shanshan Wang Ruikun Guo Honghong Ren Lichuan Yang Baihai Su Jie Zhang Nanwei Tong Xin J. Zhou Mark E. Cooper |
| author_sort | Lijun Zhao |
| collection | DOAJ |
| description | Abstract Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabetic patients with biopsy-confirmed diabetic nephropathy (DN) were retrospectively analysed. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) for ESRD. Single glomerular proteomics and immunohistochemistry were used to identify differentially expressed proteins and enriched pathways in glomeruli. During the median follow-up period of 24 months, 144 (45%) patients progressed to ESRD. In multivariable models, the Renal Pathology Society classification failed to predict ESRD, although the solidified glomerulosclerosis (score 1: HR 1.65, 95% confidence interval [CI] 1.04–2.60; score 2: HR 2.48, 95% CI 1.40–4.37) and extracapillary hypercellularity (HR 2.68, 95% CI 1.55–4.62) were identified as independent risk factors. Additionally, single glomerular proteomics, combined with immunohistochemistry, revealed that complement C9 and apolipoprotein E were highly expressed in solidified glomerulosclerosis. Therefore, solidified glomerulosclerosis and extracapillary hypercellularity predict diabetic ESRD in Chinese patients. Single glomerular proteomics identified solidified glomerulosclerosis as a unique pathological change that may be associated with complement overactivation and abnormal lipid metabolism. |
| first_indexed | 2024-12-20T16:33:03Z |
| format | Article |
| id | doaj.art-02ce83013d294e51936241f14a7d3285 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T16:33:03Z |
| publishDate | 2021-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-02ce83013d294e51936241f14a7d32852022-12-21T19:33:13ZengNature PortfolioScientific Reports2045-23222021-02-0111111410.1038/s41598-021-83856-zSolidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetesLijun Zhao0Fang Liu1Lin Li2Junlin Zhang3Tingli Wang4Rui Zhang5Wei Zhang6Xiaoyan Yang7Xiaoxi Zeng8Yiting Wang9Yucheng Wu10Hao Yang11Shisheng Wang12Yi Zhong13Huan Xu14Shanshan Wang15Ruikun Guo16Honghong Ren17Lichuan Yang18Baihai Su19Jie Zhang20Nanwei Tong21Xin J. Zhou22Mark E. Cooper23Division of Nephrology, West China Hospital of Sichuan UniversityDivision of Nephrology, West China Hospital of Sichuan UniversityDivision of Pathology, West China Hospital of Sichuan UniversityDivision of Nephrology, West China Hospital of Sichuan UniversityDivision of Nephrology, West China Hospital of Sichuan UniversityDivision of Nephrology, West China Hospital of Sichuan UniversityWest China Biomedical Big Data Center, West China Hospital/ West China School of Medicine of Sichuan UniversityWest China Biomedical Big Data Center, West China Hospital/ West China School of Medicine of Sichuan UniversityWest China Biomedical Big Data Center, West China Hospital/ West China School of Medicine of Sichuan UniversityDivision of Nephrology, West China Hospital of Sichuan UniversityDivision of Nephrology, West China Hospital of Sichuan UniversityKey Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, West China Hospital of Sichuan UniversityWest China-Washington Mitochondria and Metabolism Research Center, West China Hospital of Sichuan UniversityWest China-Washington Mitochondria and Metabolism Research Center, West China Hospital of Sichuan UniversityDivision of Pathology, West China Hospital of Sichuan UniversityDivision of Nephrology, West China Hospital of Sichuan UniversityDivision of Nephrology, West China Hospital of Sichuan UniversityDivision of Nephrology, West China Hospital of Sichuan UniversityDivision of Nephrology, West China Hospital of Sichuan UniversityDivision of Nephrology, West China Hospital of Sichuan UniversityKey Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, West China Hospital of Sichuan UniversityDivision of Endocrinology, West China Hospital of Sichuan UniversityDepartment of Pathology, Baylor University Medical Center at DallasDepartment of Diabetes, Central Clinical School, Monash UniversityAbstract Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabetic patients with biopsy-confirmed diabetic nephropathy (DN) were retrospectively analysed. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) for ESRD. Single glomerular proteomics and immunohistochemistry were used to identify differentially expressed proteins and enriched pathways in glomeruli. During the median follow-up period of 24 months, 144 (45%) patients progressed to ESRD. In multivariable models, the Renal Pathology Society classification failed to predict ESRD, although the solidified glomerulosclerosis (score 1: HR 1.65, 95% confidence interval [CI] 1.04–2.60; score 2: HR 2.48, 95% CI 1.40–4.37) and extracapillary hypercellularity (HR 2.68, 95% CI 1.55–4.62) were identified as independent risk factors. Additionally, single glomerular proteomics, combined with immunohistochemistry, revealed that complement C9 and apolipoprotein E were highly expressed in solidified glomerulosclerosis. Therefore, solidified glomerulosclerosis and extracapillary hypercellularity predict diabetic ESRD in Chinese patients. Single glomerular proteomics identified solidified glomerulosclerosis as a unique pathological change that may be associated with complement overactivation and abnormal lipid metabolism.https://doi.org/10.1038/s41598-021-83856-z |
| spellingShingle | Lijun Zhao Fang Liu Lin Li Junlin Zhang Tingli Wang Rui Zhang Wei Zhang Xiaoyan Yang Xiaoxi Zeng Yiting Wang Yucheng Wu Hao Yang Shisheng Wang Yi Zhong Huan Xu Shanshan Wang Ruikun Guo Honghong Ren Lichuan Yang Baihai Su Jie Zhang Nanwei Tong Xin J. Zhou Mark E. Cooper Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes Scientific Reports |
| title | Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes |
| title_full | Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes |
| title_fullStr | Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes |
| title_full_unstemmed | Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes |
| title_short | Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes |
| title_sort | solidified glomerulosclerosis identified using single glomerular proteomics predicts end stage renal disease in chinese patients with type 2 diabetes |
| url | https://doi.org/10.1038/s41598-021-83856-z |
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