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Predictors of poor kidney outcome in children with C3 glomerulopathy

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Abstract

Background

C3 glomerulopathy (C3G) is characterized by heterogeneous clinical presentation, outcome, and predominant C3 accumulation in glomeruli without significant IgG. There is scarce outcome data regarding childhood C3G. We describe clinical and pathological features, treatment and outcomes, and risk factors for progression to chronic kidney disease stage 5 (CKD5) in the largest pediatric series with biopsy-proven C3G.

Methods

Sixty pediatric patients with C3G from 21 referral centers in Turkey were included in this retrospective study. Patients were categorized according to CKD stage at last visit as CKD5 or non-CKD5. Demographic data, clinicopathologic findings, treatment, and outcome data were compared and possible risk factors for CKD5 progression determined using Cox proportional hazards model.

Results

Mean age at diagnosis was 10.6 ± 3.0 years and follow-up time 48.3 ± 36.3 months. Almost half the patients had gross hematuria and hypertension at diagnosis. Nephritic-nephrotic syndrome was the commonest presenting feature (41.6%) and 1/5 of patients presented with nephrotic syndrome. Membranoproliferative glomerulonephritis was the leading injury pattern, while 40 patients had only C3 staining. Patients with DDD had significantly lower baseline serum albumin compared with C3GN. Eighteen patients received eculizumab. Clinical remission was achieved in 68.3%. At last follow-up, 10 patients (16.6%) developed CKD5: they had lower baseline eGFR and albumin and higher frequency of nephrotic syndrome and dialysis requirement than non-CKD5 patients. Lower serum albumin and eGFR at diagnosis were independent predictors for CKD5 development.

Conclusions

Children with C3G who have impaired kidney function and hypoalbuminemia at diagnosis should be carefully monitored for risk of progression to CKD5.

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References

  1. Pickering MC, D’agati VD, Nester CM, Smith RJ, Haas M, Appel GB, Alpers CE, Bajema IM, Bedrosian C, Braun M, Doyle M, Fakhouri F, Fervenza FC, Fogo AB, Fremeaux-Bacchi V, Gale DP, Jorge EG, Harris CL, Holers VM, Johnson S, Lavin PJ, Medjeral-Thomas N, Morgan BP, Nast CC, Noel L, Peters DK, Cordoba SR, Servais A, Sethi S, Song WC, Tamburini P, Thurman JM, Zavros M, Cook HT (2013) C3 glomerulopathy: consensus report. Kidney Int 84:1079–1089

    Article  Google Scholar 

  2. Nester CM, Smith RJ (2013) Treatment options for C3 glomerulopathy. Curr Opin Nephrol Hypertens 22:231–237

    Article  Google Scholar 

  3. Fakhouri F, Frémeaux-Bacchi V, Noël LH, Cook HT, Pickering MC (2010) C3 glomerulopathy: a new classification. Nat Rev Nephrol 6:494–499

    Article  CAS  Google Scholar 

  4. Rabasco C, Cavero T, Román E, Rojas-Rivera J, Olea T, Espinosa M, Cabello V, Fernandez-Juarez G, Gonzales F, Avila A, Baltar MA, Diza M, Alegre R, Elias S, Anton M, Frutos MA, Pobes A, Blasco M, Martin F, Bernis C, Macias M, Barroso S, Lorenza A, Ariceta G, Lopez-Medoza M, Rivas B, Lopez-Revuelta K, Campistol JM, Mendizabal S, Cordoba SR, Praga M (2015) Effectiveness of mycophenolate mofetil in C3 glomerulonephritis. Kidney Int 88:1153–1160

    Article  CAS  Google Scholar 

  5. Medjeral-Thomas NR, O’Shaughnessy MM, O’Regan JA, Traynor C, Flanagan M, Wong L, Teoh CW, Awan A, Waldron M, Cairns T, O'Kelly P, Dorman AM, Pickering MC, Conlon PJ, Cook HT (2014) C3 glomerulopathy: clinicopathologic features and predictors of outcome. Clin J Am Soc Nephrol 9:46–53

    Article  CAS  Google Scholar 

  6. Ravindran A, Fervenza FC, Smith RJH, De Vriese AS, Sethi S (2018) C3 glomerulopathy: ten years’ experience at Mayo Clinic. Mayo Clin Proc 93:991–1008

    Article  Google Scholar 

  7. Ricklin D, Lambris JD (2016) New milestones ahead in complement-targeted therapy. Semin Immunol 28:208–222

    Article  CAS  Google Scholar 

  8. Al-Ghaithi B, Chanchlani R, Riedl M, Thorner P, Licht C (2016) C3 Glomerulopathy and post-infectious glomerulonephritis define a disease spectrum. Pediatr Nephrol 31:2079–2086

    Article  Google Scholar 

  9. Yazılıtaş F, Kargın Çakıcı E, Kurt Şükür ED, Can G, Güngör T, Orhan D, Bülbül M (2020) C3 glomerulopathy: experience of a pediatric nephrology center. Acta Clin Belg. https://doi.org/10.1080/17843286.2020.1713450

  10. Kumar A, Nada R, Ramachandran R, Rawat A, Tiewsoh K, Das R, Rayat CS, Gupta KL, Vasishta RK (2020) Outcome of C3 glomerulopathy patients: largest single-centre experience from South Asia. J Nephrol 33:539–550

    Article  CAS  Google Scholar 

  11. Pinarbasi AS, Dursun I, Poyrazoglu M, Akgun H, Bozpolat A, Dusunsel R (2020) Evaluation of the children with C3 glomerulopathy. Saudi J Kidney Dis Transpl 31:79–89

    Article  Google Scholar 

  12. Dragon-Durey M, Frmeaux-Bacchi V, Loirat C, Blouin J, Niaudet P, Deschenes G, Coppo P, Fridman WH, Weiss L (2004) Heterozygous and homozygous factor H deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis : report and genetic analysis of 16 cases. J Am Soc Nephrol 15:787–795

    Article  CAS  Google Scholar 

  13. Bomback AS, Santoriello D, Avasare RS, Regunathan-Shenk R, Canetta PA, Ahn W, Radhakrisnan J, Marasa M, Rosenstiel PE, Herlitz LC, Markowitz GS, D'Agati VD, Appel GB (2018) C3 glomerulonephritis and dense deposit disease share a similar disease course in a large United States cohort of patients with C3 glomerulopathy. Kidney Int 93:977–985

    Article  Google Scholar 

  14. Caliskan Y, Torun ES, Tiryaki TO, Oruc A, Ozluk Y, Akgul SU, Temurhan S, Oztop N, Kilicaslan I, Sever MS (2017) Immunosuppressive treatment in C3 glomerulopathy: is it really effective? Am J Nephrol 46:96–107

    Article  CAS  Google Scholar 

  15. Avasare RS, Canetta PA, Bomback AS, Marasa M, Caliskan Y, Ozluk Y, Li Y, Gharavi AG, Appel GB (2018) Mycophenolate mofetil in combination with steroids for treatment of C3 glomerulopathy: a case series. Clin J Am Soc Nephrol 213:406–413

    Article  Google Scholar 

  16. Kojc N, Bahovec A, Levart TK (2019) C3 glomerulopathy in children: is there still a place for anti-cellular immunosuppression? Nephrology 24:188–194

    Article  CAS  Google Scholar 

  17. Ravindran A, Fervenza FC, Smith RJH, Sethi S (2017) C3 glomerulonephritis with a severe crescentic phenotype. Pediatr Nephrol 32:1625–1633

    Article  Google Scholar 

  18. Kurien AA, Larsen C, Rajapurkar M, Bonsib SM, Walker P (2016) Lack of electron microscopy hinders correct renal biopsy diagnosis: a study from India. Ultrastruct Pathol 40:14–17

    Article  Google Scholar 

  19. Sethi S, Fervenza FC, Zhang Y, Zand L, Meyer NC, Borsa N, Nasr SH, Smith RJ (2013) Atypical postinfectious glomerulonephritis is associated with abnormalities in the alternative pathway of complement. Kidney Int 83:293–299

    Article  CAS  Google Scholar 

  20. Sethi S, Nester CM, Smith RJH (2012) Membranoproliferative glomerulonephritis and C3 glomerulopathy: resolving the confusion. Kidney Int 81:434–441

    Article  Google Scholar 

  21. Koopman JJE, Vries APJ, De Bajema IM (2019) C3 glomerulopathy. Nephrol Dial Transplant:gfz201. https://doi.org/10.1093/ndt/gfz201

  22. Dimkovic N, Jovanovic D, Kovacevic Z, Rabrenovic V, Nesic V, Savin M, Mitic B, Ratkovic M, Curis S, Mitic I, Pljesa S, Perunici-pekovic G, Marinkovic J, Popovic J, Vujic D (2009) Mycophenolate mofetil in high-risk patients with primary glomerulonephritis: results of a 1-year prospective study. Nephron Clin Pract 111:189–196

    Article  Google Scholar 

  23. Holle J, Berenberg-Goßler L, Wu K, Beringer O, Kropp F, Müller D, Thumfart J (2018) Outcome of membranoproliferative glomerulonephritis and C3-glomerulopathy in children and adolescents. Pediatr Nephrol 33:2289–2298

    Article  Google Scholar 

  24. Gellermann J, Weber L, Pape L, Tönshoff B, Hoyer P, Querfeld U (2013) Mycophenolate mofetil versus cyclosporin a in children with frequently relapsing nephrotic syndrome. J Am Soc Nephrol 24:1689–1697

    Article  CAS  Google Scholar 

  25. Vivarelli M, Emma F (2014) Treatment of C3 glomerulopathy with complement blockers. Semin Thromb Hemost 40:472–477

    Article  CAS  Google Scholar 

  26. Vivarelli M, Pasini A, Emma F (2012) Eculizumab for the treatment of dense-deposit disease. N Engl J Med 366:1163–1165

    Article  CAS  Google Scholar 

  27. Daina E, Noris M, Remuzzi G (2012) Eculizumab in a patient with dense-deposit disease. N Engl J Med 366:1161–1163

    Article  CAS  Google Scholar 

  28. Le Quintrec M, Lapeyraque A, Lionet A, Sellier-leclerc A, Delmas Y, Baudouin V, Daugas E, Decramer S, Tricot L, Cailliez M, Dubot P, Servais A, Mourey-Epron C, Pourcine F, Loirat C, Frémeaux-Bacchi V, Fakhouri F (2018) Patterns of clinical response to eculizumab in patients with C3 glomerulopathy. Am J Kidney Dis 72:84–92

    Article  Google Scholar 

  29. Bomback AS, Smith RJ, Barile GR, Zhang Y, Heher EC, Herlitz L, Stokes MB, Markowitz GS, D'Agati VD, Canetta PA, Radhakrishnan J, Appel GB (2012) Eculizumab for dense deposit disease and C3 glomerulonephritis. Clin J Am Soc Nephrol 7:748–756

    Article  CAS  Google Scholar 

  30. Lebreton C, Bacchetta J, Dijoud F, Bessenay L, Fremeaux-Bacchi V, Sellier-Leclerc AL (2017) C3 glomerulopathy and eculizumab: a report on four paediatric cases. Pediatr Nephrol 32:1023–1028

    Article  Google Scholar 

  31. Barbour S, Gill JS (2015) Advances in the understanding of complement mediated glomerular disease: implications for recurrence in the transplant setting. Am J Transplant 15:312–319

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Prof. Ahmet Ozturk and Dr. Sumeyra Cicek Ozdemir who helped us in statistical analysis.

Author information

Author notes

  1. Ayşe Seda Pınarbaşı and Ismail Dursun contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatric Nephrology, Erciyes University, Faculty of Medicine, Kayseri, Turkey

    Ayşe Seda Pınarbaşı, Ismail Dursun & Ruhan Düşünsel

  2. Department of Pediatric Nephrology, Faculty of Medicine, Marmara University, İstanbul, Turkey

    Ibrahim Gokce & Neslihan Çiçek

  3. Department of Pediatric Nephrology, Faculty of Medicine, Akdeniz University, Antalya, Turkey

    Elif Çomak & Mustafa Koyun

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

    Seha Saygılı & Nur Canpolat

  5. Department of Pediatric Nephrology, Faculty of Medicine, Dokuz Eylül University, İzmir, Turkey

    Meral Torun Bayram & Alper Soylu

  6. Department of Pediatric Nephrology, Faculty of Medicine, Uludağ University, Bursa, Turkey

    Osman Donmez

  7. Department of Pediatric Nephrology, Faculty of Medicine, Cukurova University, Adana, Turkey

    Engin Melek

  8. Department of Pediatric Nephrology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey

    Demet Tekcan

  9. Department of Pediatric Nephrology, Faculty of Medicine, Adnan Menderes University, Aydın, Turkey

    Dilek Yılmaz

  10. Department of Pediatric Nephrology, Faculty of Medicine, İnönü University, Malatya, Turkey

    Yılmaz Tabel

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

    Zeynep Y. Yıldırım

  12. Department of Pediatric Nephrology, Faculty of Medicine, Karadeniz Teknik University, Trabzon, Turkey

    Elif Bahat

  13. Department of Pediatric Nephrology, University of Health Sciences, Haseki Education and Research Hospital, İstanbul, Turkey

    Bağdagül Aksu

  14. Department of Pediatric Nephrology, Faculty of Medicine, Kocaeli University, İzmit, Kocaeli, Turkey

    Mehtap Ezel Çelakıl

  15. Department of Pediatric Nephrology, Faculty of Medicine, Koç University, İstanbul, Turkey

    Mehmet Taşdemir

  16. Department of Pediatric Nephrology, Bakırköy Dr Sadi Konuk Training and Research Hospital, İstanbul, Turkey

    Meryem Benzer

  17. Department of Pediatric Nephrology, University of Health Sciences, Sisli Hamidiye Etfal Training and Research Hospital, İstanbul, Turkey

    Gül Özçelik

  18. Department of Pediatric Nephrology, Faculty of Medicine, Gazi University, Ankara, Turkey

    Sevcan A. Bakkaloğlu

Authors
  1. Ayşe Seda Pınarbaşı
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Contributions

A.S.P, I.D, and R.D designed the study. A.S.P, I.D, I.G, E.Ç, S.S, M.T.B, O.D, E.M, D.T, N.Ç. D.Y, S.A.B, Y.T, Z.Y.Y, E.B, M.K, A.S, N.C, B.A, M.E.Ç, M.T, M.B, G.Ö, and RD carried out the recruitment of patients into the study. I.D and A.S.P analyzed, interpreted the data, and wrote the article. All the authors reviewed and revised the article and approved the final version.

Corresponding author

Correspondence to Ismail Dursun.

Ethics declarations

The study protocol was approved by the local institutional Ethics Committee (2017/209).

Conflict of interest

The authors declare that they have no competing interests and they have not received any funds or grants for this manuscript. The results presented in this paper have not been published previously in whole or part, except in abstract format.

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Pınarbaşı, A.S., Dursun, I., Gokce, I. et al. Predictors of poor kidney outcome in children with C3 glomerulopathy. Pediatr Nephrol 36, 1195–1205 (2021). https://doi.org/10.1007/s00467-020-04799-7

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