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...
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Nature Portfolio
2021
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oai:doaj.org-article:02ce83013d294e51936241f14a7d32852021-12-02T13:19:31ZSolidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes10.1038/s41598-021-83856-z2045-2322https://doaj.org/article/02ce83013d294e51936241f14a7d32852021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83856-zhttps://doaj.org/toc/2045-2322Abstract 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.Lijun ZhaoFang LiuLin LiJunlin ZhangTingli WangRui ZhangWei ZhangXiaoyan YangXiaoxi ZengYiting WangYucheng WuHao YangShisheng WangYi ZhongHuan XuShanshan WangRuikun GuoHonghong RenLichuan YangBaihai SuJie ZhangNanwei TongXin J. ZhouMark E. CooperNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
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Medicine R Science Q 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 |
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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. |
format |
article |
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 |
title |
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_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_sort |
solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in chinese patients with type 2 diabetes |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/02ce83013d294e51936241f14a7d3285 |
work_keys_str_mv |
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