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Clinical and histopathological prognostic factors affecting the renal outcomes in childhood ANCA-associated vasculitis

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Abstract

Objective

Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides (AAV) are very rare in childhood with an increased risk of morbidity and mortality. We aimed to evaluate renal prognostic factors in childhood AAV from the perspective of ANCA serotype, histopathological classification, and five-factor score (FFS).

Methods

Pediatric AAV patients from 11 referral centers in Turkey had been included to the study. The demographics, clinical findings, AAV subtypes, outcomes, and FFS were evaluated retrospectively. Kidney biopsies were classified histopathologically.

Results

Totally, 39 patients were enrolled in the study. Among all patients, 74.4% had renal involvement, 56.4% ear-throat-nose involvement, and 51.3% had musculoskeletal involvement. Proteinase 3 (PR3)-ANCA was positive in 48.7%, and myeloperoxidase (MPO)-ANCA was positive in 30.8%. 69.2% of patients had impaired renal function, and 28.2% had progressed to end-stage renal disease (ESRD) during the follow-up. At the time of diagnosis, FFS was ≥ 2 in 53.8%. The most common histopathologic classifications were as follows: crescentic type in 40.7% and sclerotic type in 25.9%. Gastrointestinal and renal involvement, MPO-ANCA positivity, serum creatinine levels, and impaired renal function during the follow-up were significantly higher in patients with FFS ≥ 2, compared to patients with FFS < 2. Patients with FFS ≥ 2 had more common crescentic, mixed and sclerotic histopathologic findings in biopsies. By logistic regression analysis forward method, the strongest single-risk factor among all the parameters was the initial level of creatinine in patients with ESRD, compared to the other patients (p = 0,007).

Conclusions

Evaluation of the FFS, ANCA serology, and the creatinine levels may help to predict renal prognosis.

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References

  1. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA (2013) 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 65:1–11

    Article  CAS  PubMed  Google Scholar 

  2. Akikusa JD, Schneider R, Harvey EA, Hebert D, Thorner PS, Laxer RM, Silverman ED (2007) Clinical features and outcome of pediatric Wegener’s granulomatosis. Arthritis Rheum 57:837–844

    Article  CAS  PubMed  Google Scholar 

  3. Rottem M, Fauci AS, Hallahan CW, Kerr GS, Lebovics R, Leavitt RY, Hoffman GS (1993) Wegener granulomatosis in children and adolescents: clinical presentation and outcome. J Pediatr 122:26–31

    Article  CAS  PubMed  Google Scholar 

  4. Kouri AM, Andreoli SP (2017) Clinical presentation and outcome of pediatric ANCA-associated glomerulonephritis. Pediatr Nephrol 32:449–455

    Article  PubMed  Google Scholar 

  5. Noone DG, Twilt M, Hayes WN, Thorner PS, Benseler S, Laxer RM, Parekh RS, Herbert D (2014) The new histopathologic classification of ANCA-associated GN and its association with renal outcomes in childhood. Clin J Am Soc Nephrol 9:1684–1691

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ford SL, Polkinghorne KR, Longano A, Dowling J, Dayan S, Kerr PG, Holdsworth SR, Kitching AR, Summers SA (2014) Histopathologic and clinical predictors of kidney outcomes in ANCA-associated vasculitis. Am J Kidney Dis 63:227–235

    Article  PubMed  Google Scholar 

  7. Guillevin L, Pagnoux C, Seror R, Mahr A, Mouthon L, Le Toumelin P, French Vasculitis Study Group (FVSG) (2011) The five-factor score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine 90:19–27

    Article  PubMed  Google Scholar 

  8. Berden AE, Ferrario F, Hagen EC, Jayne DR, Jennette JC, Joh K, Neumann I, Noël LH, Pusey CD, Waldherr R, Bruijn JA, Bajema IM (2010) Histopathologic classification of ANCA-associated glomerulonephritis. J Am Soc Nephrol 21:1628–1636

    Article  PubMed  Google Scholar 

  9. Bjorneklett R, Sriskandarajah S, Bostad L (2016) Prognostic value of histologic classification of ANCA-associated glomerulonephritis. Clin J Am Soc Nephrol 11:2159–2167

    Article  PubMed  PubMed Central  Google Scholar 

  10. Chen YX, Xu J, Pan XX, Shen PY, Li X, Ren H, Chen XN, Ni LY, Zhang W, Chen N (2017) Histopathological classification and renal outcome in patients with antineutrophil cytoplasmic antibodies-associated renal vasculitis: a study of 186 patients and metaanalysis. J Rheumatol 44:304–313

    Article  PubMed  Google Scholar 

  11. Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, Buoncompagni A, Lazar C, Bilge I, Uziel Y, Rigante D, Cantarini L, Hilario MO, Silva CA, Alegria M, Norambuena X, Belot A, Berkun Y, Estrella AI, Olivieri AN, Alpigiani MG, Rumba I, Sztajnbok F, Tambic-Bukovac L, Breda L, Al-Mayouf S, Mihaylova D, Chasnyk V, Sengler C, Klein-Gitelman M, Djeddi D, Nuno L, Pruunsild C, Brunner J, Kondi A, Pagava K, Pederzoli S, Martini A, Ruperto N, Paediatric Rheumatology International Trials Organisation (PRINTO) (2010) EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis 69:798–806

    Article  PubMed  Google Scholar 

  12. Ozen S, Ruperto N, Dillon MJ, Bagga A, Barron K, Davin JC, Kawasaki T, Lindsley C, Petty RE, Prieur AM, Ravelli A, Woo P (2006) EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides. Ann Rheum Dis 65:936–941

    Article  CAS  PubMed  Google Scholar 

  13. Masi AT, Hunder GG, Lie JT, Michel BA, Bloch DA, Arend WP, Calabrese LH, Edworthy SM, Fauci AS, Leavitt RY, Lightfoot RW, McShane DJ, Mills JA, Stevens MB, Wallace SL, Zvaifle NJ (1990) The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 33:1094–1100

    Article  CAS  PubMed  Google Scholar 

  14. Guillevin L, Lhote F, Gayraud M, Cohen P, Jarrousse B, Lortholary O, Thibult N, Casassus P (1996) Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. A prospective study in 342 patients. Medicine 75:7–28

    Article  Google Scholar 

  15. Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637

    Article  PubMed  PubMed Central  Google Scholar 

  16. Hellmich B, Flossmann O, Gross WL, Bacon P, Cohen-Tervaert JW, Guillevin L, Jayne D, Mahr A, Merkel PA, Raspe H, Scott DG, Witter J, Yazici H (2007) EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis. Ann Rheum Dis 66:605–617

    Article  CAS  PubMed  Google Scholar 

  17. Ozen S, Bakkaloglu A, Dusunsel R, Soylemezoglu O, Ozaltin F, Poyrazoglu H, Kasapcopur O, Ozkaya O, Yalcinkaya F, Balat A, Kural N, Donmez O, Alpay H, Anarat A, Mir S, Gur-Guven A, Sonmez F, Gok F, Turkish Pediatric Vasculitis Study Group (2007) Childhood vasculitides in Turkey: a nationwide survey. Clin Rheumatol 26:196–200

    PubMed  Google Scholar 

  18. Bowyer S, Roettcher P (1996) Pediatric rheumatology clinic populations in the United States: results of a 3 year survey. Pediatric Rheumatology Database Research Group. J Rheumatol 23:1968–7194

    CAS  PubMed  Google Scholar 

  19. Malleson PN, Fung MY, Rosenberg AM (1996) The incidence of pediatric rheumatic diseases: results from the Canadian Pediatric Rheumatology Association Disease Registry. J Rheumatol 23:1981–1987

    CAS  PubMed  Google Scholar 

  20. Sacri AS, Chambaraud T, Ranchin B, Florkin B, Sée H, Decramer S, Flodrops H, Ulinski T, Allain-Launay E, Boyer O, Dunand O, Fischbach M, Hachulla E, Pietrement C, Le Pogamp P, Stephan JL, Belot A, Nivet H, Nobili F, Guillevin L, Quartier P, Deschênes G, Salomon R, Essig M, Harambat J (2015) Clinical characteristics and outcomes of childhood-onset ANCA-associated vasculitis: a French nationwide study. Nephrol Dial Transplant 30:104–112

    Google Scholar 

  21. Cabral DA, Canter DL, Muscal E, Nanda K, Wahezi DM, Spalding SJ, Twilt M, Benseler SM, Campillo S, Charuvanij S, Dancey P, Eberhard BA, Elder ME, Hersh A, Higgins GC, Huber AM, Khubchandani R, Kim S, Klein-Gitelman M, Kostik MM, Lawson EF, Lee T, Lubieniecka JM, McCurdy D, Moorthy LN, Morishita KA, Nielsen SM, O'Neil KM, Reiff A, Ristic G, Robinson AB, Sarmiento A, Shenoi S, Toth MB, Van Mater HA, Wagner-Weiner L, Weiss JE, White AJ, Yeung RS, ARChiVe Investigators Network within the PedVas Initiative (2016) Comparing presenting clinical features in 48 children with microscopic polyangiitis to 183 children who have granulomatosis with polyangiitis (Wegener’s): an ARChiVe cohort study. Arthritis Rheum 68:2514–2526

    Article  CAS  Google Scholar 

  22. Zwerina J, Eger G, Englbrecht M, Manger B, Schett G (2009) Churg-Strauss syndrome in childhood: a systematic literature review and clinical comparison with adult patients. Semin Arthritis Rheum 39:108–115

    Article  PubMed  Google Scholar 

  23. Gendelman S, Zeft A, Spalding SJ (2013) Childhood-onset eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome): a contemporary single-center cohort. J Rheumatol 40:29–35

    Article  CAS  Google Scholar 

  24. Lionaki S, Blyth ER, Hogan SL, Hu Y, Senior BA, Jennette CE, Nachman PH, Jennette JC, Falk RJ (2012) Classification of antineutrophil cytoplasmic autoantibody vasculitides: the role of antineutrophil cytoplasmic autoantibody specificity for myeloperoxidase or proteinase 3 in disease recognition and prognosis. Arthritis Rheum 64:3452–3462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Quintana LF, Peréz NS, De Sousa E, Rodas LM, Griffiths MH, Solé M, Jayne D (2014) ANCA serotype and histopathological classification for the prediction of renal outcome in ANCA-associated glomerulonephritis. Nephrol Dial Transplant 29:1764–1769

    Article  CAS  PubMed  Google Scholar 

  26. Chang DY, Wu LH, Liu G, Chen M, Kallenberg CG, Zhao MH (2012) Re-evaluation of the histopathologic classification of ANCA-associated glomerulonephritis: a study of 121 patients in a single center. Nephrol Dial Transplant 27:2343–2349

    Article  PubMed  Google Scholar 

  27. Hattori M, Kurayama H, Koitabashi Y, Japanese Society for Pediatric Nephrology (2001) Antineutrophil cytoplasmic autoantibody-associated glomerulonephritis in children. J Am Soc Nephrol 12:1493–1500

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatric Nephrology, SBÜ. Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey

    Gül Özçelik

  2. Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey

    Hafize Emine Sönmez, Yelda Bilginer & Seza Özen

  3. Department of Pediatric Rheumatology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey

    Sezgin Şahin, Kenan Barut, Amra Adroviç & Özgür Kasapçopur

  4. Department of Pathology, SBÜ. Sisli Etfal Training and Research Hospital, Istanbul, Turkey

    Ayşim Özağarı

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

    Meral Torun Bayram

  6. Department of Pediatric Nephrology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey

    Rümeysa Yasemin Çiçek

  7. Department of Pediatric Nephrology, SBÜ. Dr. Sami Ulus Training and Research Hospital, Istanbul, Turkey

    Evrim Kargın Çakıcı

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

    Elif Çomak

  9. Department of Pediatric Nephrology and Rheumatology, Erciyes University Faculty of Medicine, Kayseri, Turkey

    Nihal Şahin & Ruhan Düşünsel

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

    Sevcan Bakkaloğlu

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

    İbrahim Gökçe & Harika Alpay

  12. Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey

    Ali Düzova & Rezan Topaloğlu

  13. Department of Pediatric Rheumatology, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey

    Ceyhun Açarı & Erbil Ünsal

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

    Engin Melek

  15. Department of Pediatric Nephrology, Gaziantep University Faculty of Medicine, Gaziantep, Turkey

    Beltinge Demircioğlu Kılıç

  16. Department of Pediatric Rheumatology, SBÜ. Dr. Sami Ulus Training and Research Hospital, Istanbul, Turkey

    Semanur Özdel

  17. Department of Pediatrics, Division of Rheumatology, Hacettepe University Faculty of Medicine, 06100, Ankara, Turkey

    Diclehan Orhan

  18. Department of Pediatric Pathology, Hacettepe University Faculty of Medicine, Ankara, Turkey

    Seza Özen

Authors
  1. Gül Özçelik
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  2. Hafize Emine Sönmez
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  15. Ceyhun Açarı
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  16. Engin Melek
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  20. Özgür Kasapçopur
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  21. Erbil Ünsal
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  22. Harika Alpay
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  23. Diclehan Orhan
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  24. Rezan Topaloğlu
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  25. Ruhan Düşünsel
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  26. Seza Özen
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Correspondence to Seza Özen.

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Özçelik, G., Sönmez, H.E., Şahin, S. et al. Clinical and histopathological prognostic factors affecting the renal outcomes in childhood ANCA-associated vasculitis. Pediatr Nephrol 34, 847–854 (2019). https://doi.org/10.1007/s00467-018-4162-5

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  • DOI: https://doi.org/10.1007/s00467-018-4162-5

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