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Mesangial C3 deposition and serum C3 levels predict renal outcome in IgA nephropathy

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Abstract

Background

Complement activation plays an important role in the pathogenesis of IgA nephropathy (IgAN). We aimed to evaluate the relationship between mesangial C3 deposition and histologic lesions and to investigate the role of mesangial C3 deposition and serum C3 reduction in predicting renal outcome in IgAN children.

Methods

We performed a retrospective cohort study in children with biopsy-proven IgAN. Mesangial C3 deposition (< 2+ vs. ≥ 2+) was detected by the immunofluorescence. Histopathologic kidney grades were determined by the Oxford classification. A decreased serum C3 concentration (hypoC3) was defined when C3 < 90 mg/dl. The endpoint was composite kidney outcome with either a 30% decline in glomerular filtration rates from baseline or kidney failure during the follow-up period.

Results

A total of 98 children were analyzed. Mesangial hypercellularity (M) was an independent factor associated with mesangial C3 deposition (HR 3.267; 95% CI 1.028–10.389; P = 0.045). After a median follow-up period of 25 months (interquartile range 18–36 months), 6 (6.1%) children reached the endpoint. Compared with other children, a significantly higher proportion of children with composite kidney outcomes had mesangial C3 deposition ≥ 2+ and hypoC3 (3.4% versus 27.3%, P = 0.002). After adjustment for clinicopathologic risk factors, mesangial C3 deposition ≥ 2+ and hypoC3 were associated with renal outcome (HR 9.772; 95% CI 1.264–75.518; P = 0.029).

Conclusion

Mesangial C3 deposition was associated with M in IgAN. Mesangial C3 deposition and hypoC3 were risk factors for renal outcome in children with IgAN.

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Acknowledgements

We would like to thank all of our colleagues at the Department of Nephrology, Beijing Children's Hospital, China, for providing the information for our pediatric patients; and Dr. Nan Zhang and Dr. Xingfeng Yao of the Department of Pathology, Beijing Children’s Hospital, China, for advice regarding kidney pathology.

Funding

This work was supported by the Capital Health Research and Development of Special Grant (No. 2016-2-2094), the Research on the Application of Capital Clinical Characteristics Program of Beijing Municipal Science and Technology Commission (No. Z161100000516106), and the Project of Beijing Science and Technology Commission (No. D181100000118006).

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Authors and Affiliations

  1. Department of Nephrology, Beijing Children’s Hospital, Capital Medical University, Beijing, 100045, China

    Dan Wu, Xueqian Li, Lei Lei, Hejia Zhang, Mengmeng Tang, Jie Ni, Chen Ling, Zhi Chen & Xiaorong Liu

  2. Department of Pathology, Beijing Children’s Hospital, Capital Medical University, Beijing, 100045, China

    Xingfeng Yao & Nan Zhang

  3. Department of Nephrology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, National Clinical Research Center for Kidney Diseases, 28th Fuxing Road, Beijing, 100853, China

    Xiangmei Chen

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  1. Dan Wu
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Correspondence to Xiaorong Liu.

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Wu, D., Li, X., Yao, X. et al. Mesangial C3 deposition and serum C3 levels predict renal outcome in IgA nephropathy. Clin Exp Nephrol 25, 641–651 (2021). https://doi.org/10.1007/s10157-021-02034-7

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