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Clinical relevance of glomerular C4d deposition in children with early IgA nephropathy or Henoch-Schönlein purpura nephropathy

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Abstract

Background

Both IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephropathy (HSPN) are characterized by glomerular mesangial IgA deposition. Several large studies on adults have suggested that glomerular C4d deposition has prognostic value in IgAN. However, there are few relevant studies on the clinical value of C4d deposition in children with IgAN or HSPN.

Methods

We performed a retrospective cohort study in pediatric patients with IgAN or HSPN. Clinicopathological data were collected at the time of kidney biopsy. Kidney C4d deposition was analyzed by immunohistochemistry. The end point was defined as a ≥ 20% decrease in estimated glomerular filtration from baseline.

Results

We enrolled 75 children, including 36 children with IgAN and 39 with HSPN. The prevalence of C4d deposition was 36% (27/75). C4d deposition was more abundant in children with proteinuria ≥ 50 mg/kg/day (51.9% versus 20.8%, P = 0.006) or nephrotic syndrome (37.0% versus 10.4%, P = 0.006). Mesangial hypercellularity (hazard ratio [HR], 5.745, 95% confidence interval [CI], 1.670–19.761, P = 0.006) and IgM deposition (HR, 4.522, 95% CI, 1.321–15.478, P = 0.016) were associated with C4d deposition. After a median follow-up of 22 months, seven (19.4%) IgAN patients and one (2.6%) HSPN patient had decreased kidney function. In children with IgAN, positive C4d was associated with decreased kidney function (P = 0.047).

Conclusion

Glomerular C4d deposition was associated with mesangial hypercellularity and glomerular IgM deposition in IgAN and HSPN. Glomerular C4d deposition may be a risk factor for eGFR decline in children with IgAN.

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Acknowledgements

The Capital Health Research and Development Special Grant (No. 2016-2-2094), the Beijing Municipal Science and Technology Commission’s Research on the Application of Capital Clinical Characteristics Program (No. Z161100000516106), and the Beijing Science and Technology Commission’s Project (No. D181100000118006) all contributed to this research. We appreciate all of our colleagues from Beijing Children’s Hospital, Department of Nephrology for providing information on the pediatric patients.

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Authors and Affiliations

  1. Department I of Nephrology, Beijing Children’s Hospital, National Center for Children’s Health, Capital Medical University, Beijing, 100045, China

    Dan Wu, Lei Lei, Hejia Zhang, Zhi Chen, Jie Ni, Chen Ling & Xiaorong Liu

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

    Xingfeng Yao & Nan Zhang

  3. Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28th Fuxing Road, Beijing, 100045, China

    Xiangmei Chen

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  1. Dan Wu
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Wu, D., Lei, L., Zhang, H. et al. Clinical relevance of glomerular C4d deposition in children with early IgA nephropathy or Henoch-Schönlein purpura nephropathy. Pediatr Nephrol 38, 431–438 (2023). https://doi.org/10.1007/s00467-022-05585-3

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