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ANCA-associated glomerulonephritis/systemic vasculitis in childhood: clinical features–outcome

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Abstract

Background

Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis and systemic vasculitis (AAGNV) is uncommon in childhood.

Methods

This is a retrospective study of AAGNV cases diagnosed over a 13-year period in a tertiary pediatric nephrology department.

Results

Thirteen cases of AAGNV were identified: seven Wegener granulomatosis (WG) and six microscopic polyangiitis (MPA). Acute renal failure/nephrotic range proteinuria (NRP) was found in 77 % of the patients (4 with WG, all with MPA). Eleven (85 %) patients showed necrotizing glomerulonephritis (NGN), with ≥50 % crescents identified in nine patients (69 %) (4 with WG, 5 with MPA). Treatment with methylprednisolone, cyclophosphamide and plasma exchange resulted in extra-renal remission and antibody reduction in all patients and renal function improvement/stabilization in 77 % of the patients. Three patients, all without oliguria at presentation and few sclerotic lesions, had normal renal function at follow-up. Chronic kidney disease (CKD) stages 2 and 3–4 were observed in four (WG) and three (MPA) patients, respectively. Three patients (23 %) developed end stage renal disease: two were MPA patients with severe presentation (markedly impaired glomerular filtration rate, oliguria, NRP, crescentic NGN, glomerular sclerosis) and one was a WG patient with extensive interstitial fibrosis/tubular atrophy.

Conclusions

Severe renal involvement was more common in children with MPA than WG. Treatment with methylprednisolone, cyclophosphamide and plasma exchange induced extra-renal remission/serological response and renal function improvement/stabilization. Markedly decreased GFR, oliguria, NRP, and chronic glomerular lesions at presentation were predictors of poor outcome.

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Abbreviations

AAGNV:

ANCA-associated glomerulonephritis and systemic vasculitis

ANCA:

Antineutrophil cytoplasmic antibody

c-ANCA:

cytoplasmic ANCA

CKD:

Chronic kidney disease

CYCP:

Cyclophosphamide

eGFR:

estimated glomerular filtration rate

ELISA:

Enzyme-linked immunosorbent assay

ESRD:

End stage renal disease

MP:

Methylprednisolone

MPA:

Microscopic polyangiitis

MPO:

Myeloperoxidase

NCGN:

Necrotizing crescentic glomerulonephritis

NGN:

Necrotizing glomerulonephritis

NRP:

Nephrotic range proteinuria

p-ANCA:

perinuclear ANCA

PR3:

Proteinase 3

UPr:UCr:

Urine protein to creatinine ratio

WG:

Wegener granulomatosis

References

  1. Vanoni F, Bettinelli A, Keller F, Bianchetti MG, Simonetti GD (2010) Vasculitidies associated with IgG antineutrophil cytoplasmic autoantibodies in childhood. Pediatr Nephrol 25:205–212

    Article  PubMed  Google Scholar 

  2. Jannette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, Hagen EC, Hoffman GS, Hunder GG, Kallenberg CG, McCluskey R, Sinico A, Rees AJ, Van Es LA, Waldherr R, Wiik A (1994) Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 37:187–192

    Article  Google Scholar 

  3. 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  PubMed  CAS  Google Scholar 

  4. Dillon MJ, Ozen S (2006) A new international classification of childhood vasculitis. Pediatr Nephrol 21:1219–1222

    Article  PubMed  Google Scholar 

  5. 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  PubMed  CAS  Google Scholar 

  6. Cabral DA, Uribe AG, Benseler S, O'Neil KM, Hashkes PJ, Higgins G, Zeft AS, Lovell DJ, Kingsbury DJ, Stevens A, McCurdy D, Chira P, Abramson L, Arkachaisri T, Campillo S, Eberhard A, Hersh AO, Huber AM, Kim S, Klein-Gitelman M, Levy DM, Li SC, Mason T, Dewitt EM, Muscal E, Nassi L, Reiff A, Schikler K, Singer NG, Wahezi D, Woodward A, ARChiVe (A Registry for Childhood Vasculitis: e-entry) Investigators Network (2009) Classification, presentation, and initial treatment of Wegener's granulomatosis in childhood. Arthritis Rheum 60:3413–3424

    Article  PubMed  Google Scholar 

  7. 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  PubMed  CAS  Google Scholar 

  8. Ellis EN, Wood EG, Berry P (1995) Spectrum of disease associated with anti-neutrophil cytoplasmic autoantibodies in pediatric patients. J Pediatr 126:40–43

    Article  PubMed  CAS  Google Scholar 

  9. Stegmayr BG, Gothefors L, Malmer B, Müller Wiefel DE, Nilsson K, Sundelin B (2000) Wegener granulomatosis in children and young adults. A case study of ten patients. Pediatr Nephrol 14:208–213

    Article  PubMed  CAS  Google Scholar 

  10. Deshpande PV, Gilbert R, Alton H, Milford DV (2000) Microscopic polyarteritis with renal and cerebral involvement. Pediatr Neprhol 15:134–135

    Article  CAS  Google Scholar 

  11. Bakkaloglu A, Ozen S, Baskin E, Besbas N, Gur-Guven A, Kasapçopur O, Tinaztepe K (2001) The significance of antineutrophil cytoplasmic antibody in microscopic polyangitis and classic polyarteritis nodosa. Arch Dis Child 85:427–430

    Article  PubMed  CAS  Google Scholar 

  12. Belostotsky VM, Shah V, Dillon MJ (2002) Clinical features in 17 paediatric patients with Wegener granulomatosis. Pediatr Nephrol 17:754–761

    Article  PubMed  Google Scholar 

  13. Yu F, Huang JP, Zou WZ, Zhao MH (2006) The clinical features of anti-neutrophil cytoplasmic antibody-associated systemic vasculitis in Chinese children. Pediatr Nephrol 21:497–502

    Article  PubMed  Google Scholar 

  14. Peco-Antic A, Bonaci-Nikolic B, Basta-Jovanovic G, Kostic M, Markovic-Lipkovski J, Nikolic M, Spasojevic B (2006) Childhood microscopic polyangiitis associated with MPO-ANCA. Pediatr Nephrol 21:46–53

    Article  PubMed  Google Scholar 

  15. Walters MD, Savage CO, Dillon MJ, Lockwood CM, Barratt TM (1988) Antineutrophil cytoplasm antibody in crescentic glomerulonephritis. Arch Dis Child 63:814–817

    Article  PubMed  CAS  Google Scholar 

  16. Nash MC, Jones CL, Walker RG, Powell HR (1993) Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis in children. Pediatr Nephrol 7:11–14

    Article  PubMed  CAS  Google Scholar 

  17. Valentini RP, Smoyer WE, Sedman AB, Kershaw DB, Gregory MJ, Bunchman TE (1998) Outcome of antineutrophil cytoplasmic autoantibodies-positive glomerulonephritis and vasculitis in children: a single-center experience. J Pediatr 132:325–328

    Article  PubMed  CAS  Google Scholar 

  18. 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

    PubMed  CAS  Google Scholar 

  19. 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-Schönlein 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 

  20. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114(2 Suppl 4th report):555–576

    Article  Google Scholar 

  21. Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263

    PubMed  CAS  Google Scholar 

  22. KDOQI/National Kidney Foundation (2005) K/DOQI clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease. Am J Kidney Dis 46(4 Suppl 1):S1–S121

    Google Scholar 

  23. Ozen S (2005) Problems in classifying vasculitis in children. Pediatr Nephrol 20:1214–1218

    Article  PubMed  Google Scholar 

  24. 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 

  25. Xin G, Zhao MH, Wang HY (2004) Detection rate and antigenic specificities of antineutrophil cytoplasmic antibodies in chinese patients with clinically suspected vasculitis. Clin Diagn Lab Immunol 11:559–562

    PubMed  Google Scholar 

  26. Wang Y, Zhao MH, Yu J, Xin G, Liu YC, Zhang YK, Wang HY (2004) The clinical and pathological characteristics of Chinese elderly patients with anti-neutrophil cytoplasmic autoantibodies associated small vessel vasculitis. Exp Gerontol 39:1401–1405

    Article  PubMed  CAS  Google Scholar 

  27. Abdou NI, Kullman GJ, Hoffman GS, Sharp GC, Specks U, McDonald T, Garrity J, Goeken JA, Allen NB (2002) Wegener's granulomatosis: survey of 701 patients in North America. Changes in outcome in the 1990s. J Rheumatol 29:309–316

    PubMed  Google Scholar 

  28. Watts RA, Mooney J, Skinner J, Scott DG, Macgregor AJ (2012) The contrasting epidemiology of granulomatosis with polyangiitis (Wegener's) and microscopic polyangiitis. Rheumatology (Oxford) 51:926–931

    Article  Google Scholar 

  29. Savige J, Gillis D, Benson E, Davies D, Esnault V, Falk RJ, Hagen EC, Jayne D, Jennette JC, Paspaliaris B, Pollock W, Pusey C, Savage CO, Silvestrini R, van der Woude F, Wieslander J, Wiik A (1999) International consensus statement on testing and reporting of antineutrophil cytoplasmic antibodies (ANCA). Am J Clin Pathol 111:507–513

    PubMed  CAS  Google Scholar 

  30. Savige J, Dimech W, Fritzler M, Goeken J, Hagen EC, Jannette JC, McEvoy R, Pusey C, Pollock W, Trevisin M, Wiik A, Wong R, International Group for Consensus Statement on Testing and Reporting of Antineutrophil Cytoplasmic Antibodies (ANCA) (2003) Addendum to the International Consensus Statement on testing and reporting of antineutrophil cytoplasmic antibodies. Quality control guidelines, comments, and recommendations for testing in other autoimmune diseases. Am J Clin Pathol 120:312–318

    Article  PubMed  CAS  Google Scholar 

  31. Haas M, Eustace JA (2004) Immune complex deposits in ANCA-associated crescentic glomerulonephritis: a study of 126 cases. Kidney Int 65:2145–2152

    Article  PubMed  CAS  Google Scholar 

  32. Bosch X, Guilabert A, Espinosa G, Mirapeix E (2007) Treatment of antineutrophil cytoplasmic antibody associated vasculitis: a systematic review. JAMA 298:655–669

    Article  PubMed  CAS  Google Scholar 

  33. Mukhtyar C, Guillevin L, Cid MC, Dasgupta B, de Groot K, Gross W, Hauser T, Hellmich B, Jayne D, Kallenberg CG, Merkel PA, Raspe H, Salvarani C, Scott DG, Stegeman C, Watts R, Westman K, Witter J, Yazici H, Luqmani R, European Vasculitis Study Group (2009) EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis 68:310–317

    Article  PubMed  CAS  Google Scholar 

  34. Wright E, Dillon MJ, Tullus K (2007) Childhood vasculitis and plasma exchange. Eur J Pediatr 166:145–151

    Article  PubMed  Google Scholar 

  35. Gianviti A, Trompeter RS, Barratt TM, Lythgoe MF, Dillon MJ (1996) Retrospective study of plasma exchange in patients with idiopathic rapidly progressive glomerulonephritis and vasculitis. Arch Dis Child 75:186–190

    Article  PubMed  CAS  Google Scholar 

  36. Vamvakopoulos J, Savage CO, Harper L (2010) ANCA-associated vasculitides- lessons from the adult literature. Pediatr Nephrol 25:1397–1407

    Article  PubMed  Google Scholar 

  37. Jayne D, Rasmussen N, Andrassy K, Bacon P, Tervaert JW, Dadoniené J, Ekstrand A, Gaskin G, Gregorini G, de Groot K, Gross W, Hagen EC, Mirapeix E, Pettersson E, Siegert C, Sinico A, Tesar V, Westman K, Pusey C, European Vasculitis Study Group (2003) A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 349:36–44

    Article  PubMed  CAS  Google Scholar 

  38. Hiemstra TF, Walsh M, Mahr A, Savage CO, de Groot K, Harper L, Hauser T, Neumann I, Tesar V, Wissing KM, Pagnoux C, Schmitt W, Jayne DR, European Vasculitis Study Group (EUVAS) (2010) Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA 304:2381–2388

    Article  PubMed  CAS  Google Scholar 

  39. Arulkumaran N, Jawad S, Smith SW, Harper L, Brogan P, Pusey CD, Salama AD (2011) Long-term outcome of paediatric patients with ANCA vasculitis. Pediatr Rheumatol Online J 9:12

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Nephrology, Birmingham Children’s Hospital NHS Foundation Trust, Steelhouse Lane, Birmingham, B4 6NH, UK

    Ekaterini Siomou, Despoina Tramma & David V. Milford

  2. Department of Paediatric Pathology, Birmingham Children’s Hospital NHS Foundation Trust, Steelhouse Lane, Birmingham, B4 6NH, UK

    Claire Bowen

  3. University Hospital of Ioannina, Stavros Niarchos Avenue, 45 500, Ioannina, Greece

    Ekaterini Siomou

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  1. Ekaterini Siomou
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Correspondence to Ekaterini Siomou.

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Siomou, E., Tramma, D., Bowen, C. et al. ANCA-associated glomerulonephritis/systemic vasculitis in childhood: clinical features–outcome. Pediatr Nephrol 27, 1911–1920 (2012). https://doi.org/10.1007/s00467-012-2198-5

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  • DOI: https://doi.org/10.1007/s00467-012-2198-5

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