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The clinical and laboratory features of Chinese Han anti-factor H autoantibody-associated hemolytic uremic syndrome

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Abstract

Background

Anti-complement factor H (CFH) autoantibody-associated hemolytic uremic syndrome (HUS) is a severe sub-type of HUS.

Methods

We assessed the clinical and renal pathological features, circulating complement levels, and genetic background of Chinese pediatric patients with this sub-type of HUS. Thirty-three consecutive patients with acute kidney injury who tested positive for serum anti-CFH autoantibodies were enrolled in this study.

Results

All of the eight patients who underwent renal biopsies presented with changes typical of thrombotic microangiopathy, especially changes in chronic characteristics. Compared to patients in remission and normal control subjects, patients with acute disease had significantly lower plasma CFH levels and significantly higher plasma complement 3a (C3a), C5a, and terminal complement complex (SC5b-9) levels. The CFH–anti-CFH immunoglobin G (IgG) circulating immunocomplex (CFH-CIC) titers were more closely correlated with CFH plasma levels than anti-CFH IgG levels. Of the 22 patients, four (18%) were homozygous for CFHR3–1Δ and ten were heterozygous for CFHR1 or CFHR3 deletions. Most patients responded well to a combination of plasma and immunosuppressive therapies, with a remission rate of 87%. At the end of the follow-up, nine patients reached the combined end-points, including two with end-stage renal disease and seven with relapses.

Conclusion

Plasma C3a, C5a, and SC5b-9 levels predicted disease activity in anti-CFH autoantibody-associated HUS patients enrolled in this study. These patients responded well to plasma therapy combined with immunosuppression.

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Acknowledgements

We gratefully acknowledge the contributions of Jie AO, Xin ZHENG and Lei QU of the Peking University First Hospital in our histopathological studies. This work was supported by grants from the National Natural Science Foundation of China to Innovation Research Group (No. 81321064), National Natural Science Foundation of China (No. 81470932, No.81500526, No, 81670639 and No. 81670640), The Capital Health Research and Development of Special Grant (No. 2016-2-2094) and the Research on the Application of Capital Clinical Characteristics Program of Beijing Municipal Science and Technology Commission (No. Z161100000516106).

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    Authors and Affiliations

    1. Renal Division, Department of Medicine, Peking University Institute of Nephrology, Peking University First Hospital, Beijing, People’s Republic of China

      Di Song, Wei-yi Guo, Su-xia Wang, Feng Yu & Ming-hui Zhao

    2. Key laboratory of Renal Disease, Ministry of Health of China, Beijing, People’s Republic of China

      Di Song, Wei-yi Guo, Su-xia Wang, Feng Yu & Ming-hui Zhao

    3. Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing, 100034, People’s Republic of China

      Di Song, Wei-yi Guo, Su-xia Wang, Feng Yu & Ming-hui Zhao

    4. Department of Nephrology, Beijing Children’s Hospital affiliated to Capital Medical University, West District Nan Li Shi Lu 56th, Beijing, 100045, People’s Republic of China

      Xiao-rong Liu & Zhi Chen

    5. Department of Pediatrics, Peking University First Hospital, Beijing, People’s Republic of China

      Hui-jie Xiao & Jie Ding

    6. Department of Pediatrics, Shandong Provincial Hospital affiliated with Shandong University, Jinan, People’s Republic of China

      Shu-zhen Sun

    7. Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China

      Hong-yan Liu

    8. Department of Nephrology, Peking University International Hospital, Beijing, 102206, People’s Republic of China

      Feng Yu

    9. Peking-Tsinghua Center for Life Sciences, Beijing, People’s Republic of China

      Ming-hui Zhao

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    1. Di Song
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    On Behalf of the Chinese Renal–TMA Network Institutes

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    Correspondence to Xiao-rong Liu or Feng Yu.

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    The research was in compliance with the Declaration of Helsinki Principles and approved by the local ethical committees. Informed consent of the participants or the parents of minor patients was obtained for blood sampling and renal biopsy

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    Xiao-rong Liu and Feng Yu contributed equally to this work.

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    Song, D., Liu, Xr., Chen, Z. et al. The clinical and laboratory features of Chinese Han anti-factor H autoantibody-associated hemolytic uremic syndrome. Pediatr Nephrol 32, 811–822 (2017). https://doi.org/10.1007/s00467-016-3562-7

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