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Complement gene mutations in children with C3 glomerulopathy: do they affect the response to mycophenolate mofetil?

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Abstract

Background

C3 glomerulopathy (C3G) is a complement-mediated disease. Although genetic studies are not required for diagnosis, they are valuable for treatment planning and prognosis prediction. The aim of this study is to investigate the clinical phenotypes, kidney survival, and response to mycophenolate mofetil (MMF) treatment in pediatric C3G patients with and without mutations in complement-related genes.

Methods

Sixty pediatric C3G patients were included, divided into two groups based on complement-related gene mutations. Demographic and clinical-pathological findings, treatment modalities, and outcome data were compared, and Kaplan–Meier analysis was performed for kidney survival.

Results

Out of the 60 patients, 17 had mutations. The most common mutation was in the CFH gene (47%). The mean age at diagnosis was higher in the group with mutation (12.9 ± 3.6 vs. 11.2 ± 4.1 years, p = 0.039). While the patients without mutation most frequently presented with nephritic syndrome (44.2%), the mutation group was most likely to have asymptomatic urinary abnormalities (47.1%, p = 0.043). Serum parameters and histopathological characteristics were similar, but hypoalbuminemia was more common in patients without mutation. During 45-month follow-up,10 patients progressed to chronic kidney disease stage 5 (CKD5), with 4 having genetic mutation. The time to develop CKD5 was longer in the mutation group but not significant. MMF treatment had no effect on progression in either group.

Conclusions

This study is the largest pediatric C3G study examining the relationship between genotype and phenotype. We showed that the mutation group often presented with asymptomatic urinary abnormalities, was diagnosed relatively late but was not different from the without mutation group in terms of MMF treatment response and kidney survival.

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Data availability

Data for this study may be obtained by emailing the corresponding author.

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Author information

Authors and Affiliations

  1. Department of Pediatric Nephrology, Kayseri City Training and Research Hospital, Kayseri, Turkey

    Neslihan Günay

  2. Department of Pediatric Nephrology, Erciyes University Medical Faculty, Kayseri, Turkey

    İsmail Dursun, Sibel Yel & Hakan M. Poyrazoğlu

  3. Department of Pediatric Nephrology, Marmara University Medical Faculty, Istanbul, Turkey

    İbrahim Gökçe, Neslihan Çiçek & Harika Alpay

  4. Department of Pediatric Nephrology, Gaziantep University Medical Faculty, Gaziantep, Turkey

    Mehtap Akbalık Kara & Beltinge Demircioğlu Kılıç

  5. Department of Pediatric Nephrology, Ondokuz Mayıs University Medical Faculty, Samsun, Turkey

    Demet Tekcan & Özlem Aydoğ

  6. Dokuz Eylül University Medical Faculty, Department of Pediatric Nephrology, İzmir, Turkey

    Meral Torun Bayram & Alper Soylu

  7. Department of Pediatric Nephrology, Akdeniz University Medical Faculty, Antalya, Turkey

    Mustafa Koyun & Elif Çomak

  8. Behçet Uz Pediatric Diseases Training and Research Hospital, Pediatric Nephrology Clinic, İzmir, Turkey

    Nida Dinçel & Aslı Kantar Özşahin

  9. Prof. Dr. Cemil, Taşcıoğlu City Hospital Pediatric Nephrology Clinic, Istanbul, Turkey

    Hasan Dursun & Alper Kaçar

  10. Department of Pediatric Nephrology, İstanbul University Cerrahpaşa Medical Faculty, Istanbul, Turkey

    Seha Saygılı & Nur Canpolat

  11. İstanbul Faculty of Medicine, Department of Pediatric Nephrology, İstanbul University, Istanbul, Turkey

    Zeynep Nagehan Yürük Yıldırım & Alev Yılmaz

  12. Department of Pediatric Nephrology, Pamukkale University Medical Faculty, Denizli, Turkey

    Selçuk Yüksel & İlknur Girişgen

  13. Department of Pediatric Nephrology, Uludağ University Medical Faculty, Bursa, Turkey

    Osman Dönmez & Kadirye Betül Akkoyunlu

  14. Department of Pediatric Nephrology, Çukurova University Medical Faculty, Adana, Turkey

    Bahriye Atmış

  15. Department of Pediatric Nephrology, Ankara Baskent University, Ankara, Turkey

    Aysun Çaltık Yılmaz

  16. Department of Pediatric Nephrology, Gazi University Medical Faculty, Ankara, Turkey

    Sevcan A. Bakkaloğlu

  17. Department of Pediatric Nephrology, Kocaeli University Medical Faculty, Kocaeli, Turkey

    Mehmet Baha Aytaç

  18. Department of Pediatric Nephrology, İstinye University Medical Faculty, Istanbul, Turkey

    Mehmet Taşdemir

  19. Medical Faculty Division of Pediatric Nephrology, İzmir Katip Çelebi University, İzmir, Turkey

    Belde Kasap Demir

Authors
  1. Neslihan Günay
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  2. İsmail Dursun
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  3. İbrahim Gökçe
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  30. İlknur Girişgen
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  32. Harika Alpay
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  33. Hakan M. Poyrazoğlu
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Contributions

NG, ID, and HMP designed the study. NG, ID, IG, MAK, DT, NÇ, MTB, MK, ND, HD, SS, ZNYY, SY, OD, SY, BDK, ÖA, BA, AÇY, SAB, MBA, MT, BKD, AS, EÇ, AKÖ, AK, NC, AY, IG, KBA, HA, and HMP carried out the recruitment of patients into the study. ID and NG analyzed, interpreted the data, and wrote the article. All the authors reviewed and revised the article and approved the final version.

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Correspondence to İsmail Dursun.

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Günay, N., Dursun, İ., Gökçe, İ. et al. Complement gene mutations in children with C3 glomerulopathy: do they affect the response to mycophenolate mofetil?. Pediatr Nephrol 39, 1435–1446 (2024). https://doi.org/10.1007/s00467-023-06231-2

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