SARS-CoV-2 Protein Deposition Enhances Renal Complement Activation and Aggravates Kidney Injury in Membranous Nephropathy After COVID-19

Introduction: COVID-19 has been reported to be associated with the occurrence and recurrence of membranous nephropathy (MN). The clinicopathological characteristics and complement system activation of MN after COVID-19 are unclear. Methods: A total of 38 patients with biopsy-proven MN who developed...

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Main Authors: Guoqin Wang, Lei Yang, Xiaoyi Xu, Weiyi Guo, Lijun Sun, Yanyan Wang, Wenrong Cheng, Nan Ye, Lingqiang Kong, Xiaoyi Zhao, Hong Cheng
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024924018783
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Summary:Introduction: COVID-19 has been reported to be associated with the occurrence and recurrence of membranous nephropathy (MN). The clinicopathological characteristics and complement system activation of MN after COVID-19 are unclear. Methods: A total of 38 patients with biopsy-proven MN who developed new-onset proteinuria after COVID-19 were enrolled in this study. One hundred patients with primary MN diagnosed before the COVID-19 pandemic were the control. Renal immunohistochemical staining for SARS-CoV-2 nucleocapsid protein was performed in 38 patients with MN after COVID-19. Serum membrane attack complex (MAC) was detected by enzyme-linked immunosorbent assay. Glomerular staining for the complement proteins in different pathways were detected by immunohistochemistry. Results: Thirteen of 38 patients had positive staining for SARS-CoV-2 nucleocapsid protein. Compared with the control patients, the clinical manifestations were more severe in patients after COVID-19. Patients with positive SARS-CoV-2 staining had a higher proportion of nephrotic syndrome, lower level of serum albumin, and greater severity of renal interstitial fibrosis than those of patients with negative SARS-CoV-2 staining. Serum MAC level and renal MAC staining intensity of MN after COVID-19 were significantly higher than those of the control patients. MAC expression in MN patients with positive SARS-CoV-2 staining was stronger than that in both control patients and MN after COVID-19 with negative SARS-CoV-2 staining. The expression trend of factor H was consistent with that of MAC. Conclusion: Excessive activation of the complement system aggravated symptoms in MN after COVID-19. Therapeutic strategy targeting the complement system may need to be considered.
ISSN:2468-0249