Top

Published in:

01-05-2019 | Vasculitis | Original Article

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

Authors: Gül Özçelik, Hafize Emine Sönmez, Sezgin Şahin, Ayşim Özağarı, Meral Torun Bayram, Rümeysa Yasemin Çiçek, Evrim Kargın Çakıcı, Elif Çomak, Kenan Barut, Nihal Şahin, Sevcan Bakkaloğlu, İbrahim Gökçe, Ali Düzova, Yelda Bilginer, Ceyhun Açarı, Engin Melek, Beltinge Demircioğlu Kılıç, Semanur Özdel, Amra Adroviç, Özgür Kasapçopur, Erbil Ünsal, Harika Alpay, Diclehan Orhan, Rezan Topaloğlu, Ruhan Düşünsel, Seza Özen

Published in: Pediatric Nephrology | Issue 5/2019

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.

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 65:1–11CrossRefPubMed

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 57:837–844CrossRefPubMed

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 122:26–31CrossRefPubMed

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

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 9:1684–1691CrossRefPubMedPubMedCentral

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 63:227–235CrossRefPubMed

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 90:19–27CrossRefPubMed

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 21:1628–1636CrossRefPubMed

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

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 44:304–313CrossRefPubMed

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 69:798–806CrossRefPubMed

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 65:936–941CrossRefPubMed

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 33:1094–1100CrossRefPubMed

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 75:7–28CrossRef

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 20:629–637CrossRefPubMedPubMedCentral

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 66:605–617CrossRefPubMed

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 26:196–200PubMed

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 23:1968–7194PubMed

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 23:1981–1987PubMed

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

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 68:2514–2526CrossRef

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 39:108–115CrossRefPubMed

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 40:29–35CrossRef

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 64:3452–3462CrossRefPubMedPubMedCentral

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 29:1764–1769CrossRefPubMed

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 27:2343–2349CrossRefPubMed

27.

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

Title: Clinical and histopathological prognostic factors affecting the renal outcomes in childhood ANCA-associated vasculitis
Authors: Gül Özçelik
Hafize Emine Sönmez
Sezgin Şahin
Ayşim Özağarı
Meral Torun Bayram
Rümeysa Yasemin Çiçek
Evrim Kargın Çakıcı
Elif Çomak
Kenan Barut
Nihal Şahin
Sevcan Bakkaloğlu
İbrahim Gökçe
Ali Düzova
Yelda Bilginer
Ceyhun Açarı
Engin Melek
Beltinge Demircioğlu Kılıç
Semanur Özdel
Amra Adroviç
Özgür Kasapçopur
Erbil Ünsal
Harika Alpay
Diclehan Orhan
Rezan Topaloğlu
Ruhan Düşünsel
Seza Özen
Publication date: 01-05-2019
Publisher: Springer Berlin Heidelberg
Keywords: Vasculitis
Vasculitis
Granulomatosis with Polyangiitis
Churg-Strauss Syndrome
Churg-Strauss Syndrome
Granulomatosis with Polyangiitis
Published in: Pediatric Nephrology / Issue 5/2019
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-018-4162-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Objective

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 5/2019

The aminoglycoside geneticin permits translational readthrough of the CTNS W138X nonsense mutation in fibroblasts from patients with nephropathic cystinosis

Persistent fever in a pediatric renal transplant patient: Questions

Low-dose rituximab is no less effective for nephrotic syndrome measured by 12-month outcome

Pediatric intradialytic hypotension: recommendations from the Pediatric Continuous Renal Replacement Therapy (PCRRT) Workgroup

Optimal duration of treatment with eculizumab in atypical hemolytic uremic syndrome (aHUS)—a question to be addressed in a scientific way

Chronic kidney disease following twin-to-twin transfusion syndrome—long-term outcomes