4.7 Article

Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes

Journal

SCIENTIFIC REPORTS
Volume 11, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41598-021-83856-z

Keywords

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Funding

  1. National Natural Science Foundation of China [81970626, 81670662]
  2. Key Research and Development Project of Sichuan Science Technology Department [19ZDYF1273]

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This study analyzed the histological features of 322 Chinese type 2 diabetic patients with confirmed diabetic nephropathy to identify risk factors for end-stage renal disease (ESRD). The findings showed that solidified glomerulosclerosis and extracapillary hypercellularity were independent predictors of ESRD in Chinese patients with diabetes, with complement C9 and apolipoprotein E being highly expressed in solidified glomerulosclerosis. Single glomerular proteomics identified solidified glomerulosclerosis as a unique pathological change associated with complement overactivation and abnormal lipid metabolism.
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.

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