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Association between glomerular C4d deposition, proteinuria, and disease severity in children with IgA nephropathy

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Abstract

Background

C4d may be used as a marker to evaluate the condition and prognosis of adults with IgA nephropathy, but there have been few studies of children with IgA nephropathy.

Methods

C4d immunohistochemical staining was performed on samples from children with IgA nephropathy with C1q-negative immunofluorescence. The clinical and pathological treatment and prognostic characteristics of children in the C4d-positive and -negative groups were compared.

Results

A total of sixty-five children with IgA nephropathy were included in the study and were followed up for an average of 37 months. C4d was mainly deposited along the capillary loops. The urinary protein-to-creatinine ratio (UPCR) in the C4d-positive group was significantly higher than that in the C4d-negative group (3.97 vs. 0.81, P < 0.001), and the average integrated optical density value of each child was positively correlated with the UPCR (r = 0.441, P < 0.001). There was a significant difference in the proportions of children with mesangial hypercellularity (M1) (68.97% vs. 44.44%, P = 0.048) and segmental glomerulosclerosis (S1) (65.52% vs. 33.33%, P = 0.010) between the C4d-positive group and the C4d-negative group. The proportion of children who received immunosuppressants in the C4d-positive group was higher than that in the C4d-negative group (86.21% vs. 36.11%, P < 0.001). There was no significant difference in the proportion of children developing kidney failure between the two groups.

Conclusion

C4d was found to be associated with proteinuria, segmental lesions, and immunosuppressant treatment. Activation of the lectin pathway may reflect the severity of clinical and pathological manifestations of IgA nephropathy in children.

Graphical abstract

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank Ranran Shi, Zongyan Dai, and Mengmeng Liu for their support with the study.

Funding

This study was funded by the Beijing Municipal Science & Technology Commission No. Z191100006619062, The School Health Association of Shandong No. SDWS2022157, and the Science and Technology project of Jinan Municipal Health Commission No. 2022–2-148.

Author information

Author notes

  1. Shuzhen Sun and Hui Wang contributed equally to the work.

Authors and Affiliations

  1. Department of Pediatric Nephrology, Rheumatology and Immunology, Children’s Hospital Affiliated to Shandong University, Jinan Children’s Hospital, Jinan, Shandong Province, China

    Weiran Zhou, Xuemei Liu, Hongxia Zhang, Yanyan Pan & Linlin Dong

  2. Department 2 of Nephrology, Beijing Children’s Hospital Affiliated to Capital Medical University, National Center for Children’s Health, Key Laboratory of Major Diseases in Children’s Ministry of Education, Beijing Key Laboratory of Pediatric Chronic Kidney Diseases and Blood Purification, Beijing, China

    Hui Wang, Ying Shen & Fan Duan

  3. Department of Pediatric Nephrology, Rheumatology and Immunology, Shandong Provincial Hospital, Shandong University, Jinan, China

    Shuzhen Sun

  4. Department of Pathology, Shandong University, Jinan, China

    Junhui Zhen

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  1. Weiran Zhou
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  2. Hui Wang
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Contributions

Weiran Zhou contributed to the design, research, statistical analyses, data interpretation; drafted the initial manuscript and reviewed and revised the manuscript. Dr. Wang and Dr. Sun provided guidance in the study design and critical review of the manuscript. Dr. Shen supervised the study. Dr. Liu and Hongxia Zhang organized the data and provided guidance in the study design. Dr. Zhen performed pathological evaluations. Yanyan Pan and Linlin Dong contributed to recruiting volunteer patients. Data analysis was performed by Linlin Dong and Fan Duan. All the authors approved the final manuscript for submission.

Corresponding author

Correspondence to Hui Wang.

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Ethics approval

Approval was obtained from the ethics committee of Children’s Hospital Affiliated to Shandong University. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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Informed consent was obtained from the legal guardians.

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All the authors approved the manuscript as submitted and agreed to be accountable for all aspects of the work.

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The authors declare no competing interests.

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Zhou, W., Wang, H., Sun, S. et al. Association between glomerular C4d deposition, proteinuria, and disease severity in children with IgA nephropathy. Pediatr Nephrol 38, 1147–1157 (2023). https://doi.org/10.1007/s00467-022-05725-9

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