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Low levels of complement factor C3 at diagnosis can predict outcome in antineutrophil antibody associated vasculitis

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Abstract

Introduction

Experimental data support the involvement of complement in the pathogenesis of antineutrophil antibody associated vasculitis, and clinical studies describe a more severe disease phenotype in patients with antineutrophil antibody associated vasculitis and complement activation. In the present study, we looked for an association between circulating serum complement factor 3 levels at diagnosis and outcomes.

Methods

One hundred sixty-four patients with antineutrophil antibody associated vasculitis who underwent kidney biopsy at our center during the last 15 years were retrospectively reviewed. Patients were categorized according to their serum complement factor 3 level at diagnosis. Patient and renal survival were compared between those above and below the median serum complement factor 3 at diagnosis.

Results

During the first year, 6 patients died and 53 reached end-stage renal disease. Death or end-stage renal disease at one-year were significantly more common in the low serum complement factor 3 group (44 vs. 29%, p = 0.037). In the multivariable analysis, serum complement factor 3 was the strongest negative outcome predictor (HR, 95%CI 0.118, (0.021–0.670)). The lower the serum complement factor 3 level at baseline, the higher the risk of dialysis and death. The risk was particularly high for both endpoints if the serum complement factor 3 concentration was below 0.9 g/l at baseline.

Conclusion

Complement activation at diagnosis may identify a distinct subgroup of patients with antineutrophil antibody associated vasculitis and higher risk for poor outcomes. However, it remains to be proven whether inhibition of serum complement factor 3 is beneficial and safe in the clinical setting.

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Data availability

Data can be shared, after publication, in fully anonymous form after request.

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Acknowledgements

FGS and PRM are supported by grants from the Deutsche Forschungsgemeinschaft SFB 854 (project A01; GRK 2408, project 8) and grants ME-1365/7-2 and ME-1365/9-2.

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Authors and Affiliations

  1. University Clinic for Nephrology and Hypertension, Diabetology and Endocrinology, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany

    Florian G. Scurt, Verena Hirschfeld, Maximilian Ganz & Peter R. Mertens

  2. Clinic of Orthopedics and Traumatology, St. Elisabeth Hospital Mayen, Mayen, Germany

    Verena Hirschfeld

  3. Department of Nephrology and Hypertension, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Christos Chatzikyrkou

Authors
  1. Florian G. Scurt
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  2. Verena Hirschfeld
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  3. Maximilian Ganz
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  4. Peter R. Mertens
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  5. Christos Chatzikyrkou
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Contributions

FGS and CC conceived the study. VH searched files and retrieved patient data. MJG contributed to the acquisition of patient data. CC wrote the manuscript. FGS did the statistical analysis and created the Tables and Figures. PRM read and edited the manuscript.

Corresponding authors

Correspondence to Florian G. Scurt or Christos Chatzikyrkou.

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The authors declare that they have no competing interests.

Ethical approval

The trial was conducted in accordance with local laws and the internationally accepted principles of good clinical practice, which have their origin in the Declaration of Helsinki. The local ethics committee approved the study.

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Written informed consent was obtained from each participant.

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Scurt, F.G., Hirschfeld, V., Ganz, M. et al. Low levels of complement factor C3 at diagnosis can predict outcome in antineutrophil antibody associated vasculitis. J Nephrol 36, 2281–2293 (2023). https://doi.org/10.1007/s40620-023-01683-z

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  • DOI: https://doi.org/10.1007/s40620-023-01683-z

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