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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Autores principales: 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
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Publicado: Nature Portfolio 2021
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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
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.
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
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