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Risk factors for progression in children and young adults with IgA nephropathy: an analysis of 261 cases from the VALIGA European cohort

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Pediatric Nephrology Aims and scope Submit manuscript

An Erratum to this article was published on 04 October 2016

Abstract

Background

There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease.

Methods

Data on 261 young patients [age <23 years; mean follow-up of 4.9 (range 2.5–8.1) years] enrolled in VALIGA, a study designed to validate the Oxford Classification of IgAN, were assessed. Renal biopsies were scored for the presence of mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1-2) (MEST score) and crescents (C1). Progression was assessed as end stage renal disease and/or a 50 % loss of estimated glomerular filtration rate (eGFR) (combined endpoint) as well as the rate of renal function decline (slope of eGFR). Cox regression and tree classification binary models were used and compared.

Results

In this cohort of 261 subjects aged <23 years, Cox analysis validated the MEST M, S and T scores for predicting survival to the combined endpoint but failed to prove that these scores had predictive value in the sub-group of 174 children aged <18 years. The regression tree classification indicated that patients with M1 were at risk of developing higher time-averaged proteinuria (p < 0.0001) and the combined endpoint (p < 0.001). An initial proteinuria of ≥0.4 g/day/1.73 m2 and an eGFR of <90 ml/min/1.73 m2 were determined to be risk factors in subjects with M0. Children aged <16 years with M0 and well-preserved eGFR (>90 ml/min/1.73 m2) at presentation had a significantly high probability of proteinuria remission during follow-up and a higher remission rate following treatment with corticosteroid and/or immunosuppressive therapy.

Conclusion

This new statistical approach has identified clinical and histological risk factors associated with outcome in children and young adults with IgAN.

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Acknowledgments

The study was supported by a grant from the first research call of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) in 2009. Stéphan Troyanov and John Feehally, members of the VALIGA Steering Committee are acknowledged for their helpful advice.

Author information

Authors and Affiliations

  1. Fondazione Ricerca Molinette, Nephrology, Dialysis and Transplantation, Regina Margherita Hospital, Turin, Italy

    Rosanna Coppo, Roberta R Camilla, Licia Peruzzi & Alessandro Amore

  2. Annunziata Hospital, Cosenza, Italy

    Danilo Lofaro, Teresa Papalia & Renzo Bonofiglio

  3. Oxford University Hospitals, Oxford, UK

    Shubha Bellur & Ian S. D. Roberts

  4. Toronto General Hospital, University Health Network, Toronto, Canada

    Daniel Cattran

  5. Imperial College, Hammersmith Hospital, London, UK

    H. Terence Cook

  6. Bambino Gesù Hospital, Rome, Italy

    Francesco Emma & Laura Fuiano

  7. Karolinska University Hospital, Huddinge, Sweden

    Ulla Berg & Magnus Soderberg

  8. Hacettepe University, Ankara, Turkey

    Rezan Topaloglu, Yelda. Bilginer & Diclehan Orhan

  9. University of Bari and Foggia, Bari, Italy

    Loreto Gesualdo & Anna Maria Di Palma

  10. Belcolle Hospital, Viterbo, Italy

    Rosaria Polci

  11. University of Warsaw, Warsaw, Poland

    Malgorzata Mizerska-Wasiak & Jadwiga Maldyk

  12. University of Istanbul, Istanbul, Turkey

    Yasar Caliskan & Yasemin Ozluk

  13. Karolinska Institutet, Stockholm, Sweden

    Sigrid Lundberg & Birgitta Sudelin

  14. Spedali Civili University Hospital, Brescia, Italy

    Giovanni Cancarini & Regina Tardanico

  15. Western Infirmary Glasgow, Glasgow, UK

    Colin Geddes & David Kipgen

  16. Radboud University, Nijmegen, The Netherlands

    Jack Wetzels & Eric Steenbergen

  17. Silesian University, Katowice, Poland

    Andrzej Wiecek & Henryk Karkoszka

  18. Warsaw Medical University, Warsaw, Poland

    Magdalena Durlik & Agnieszka Perkowska-Ptasinska

  19. Borgomanero Hospital, Borgomanero, Italy

    Stefano Cusinato

  20. San Giovanni Bosco Hospital, Turin, Italy

    Cristiana Rollino

  21. Hospital Maggiore di Lodi, Lodi, Italy

    Milena Maggio

  22. Hospital 12 de Octubre, Madrid, Spain

    Manuel Praga & Eduardo Gutierrez

  23. University of Uppsala, Uppsala, Sweden

    Hilde K.Smerud

  24. General University Hospital, Prague, Czech Republic

    Vladimir Tesar, Dita Maixnerova & Eva Honsova

  25. Leicester General Hospital, Leicester, UK

    Jonathan Barratt

  26. University of Turin, Turin, Italy

    Gianna Mazzucco

  27. University of Rome, Rome, Italy

    Costantinos Giannakakis

  28. Monza Hospital, Monza, Italy

    Franco Ferrario

Authors
  1. Rosanna Coppo
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  2. Danilo Lofaro
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  3. Roberta R Camilla
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  4. Shubha Bellur
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  5. Daniel Cattran
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  6. H. Terence Cook
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  7. Ian S. D. Roberts
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  8. Licia Peruzzi
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  9. Alessandro Amore
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  10. Francesco Emma
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  11. Laura Fuiano
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  12. Ulla Berg
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  13. Rezan Topaloglu
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  14. Yelda. Bilginer
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  15. Loreto Gesualdo
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  16. Rosaria Polci
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  17. Malgorzata Mizerska-Wasiak
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  18. Yasar Caliskan
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  19. Sigrid Lundberg
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  20. Giovanni Cancarini
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  21. Colin Geddes
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  26. Cristiana Rollino
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  29. Hilde K.Smerud
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  30. Vladimir Tesar
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  31. Dita Maixnerova
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  32. Jonathan Barratt
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  33. Teresa Papalia
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  34. Renzo Bonofiglio
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  35. Gianna Mazzucco
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  36. Costantinos Giannakakis
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  37. Magnus Soderberg
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  38. Diclehan Orhan
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  39. Anna Maria Di Palma
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  40. Jadwiga Maldyk
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  41. Yasemin Ozluk
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  42. Birgitta Sudelin
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  43. Regina Tardanico
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  44. David Kipgen
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  45. Eric Steenbergen
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  46. Henryk Karkoszka
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  47. Agnieszka Perkowska-Ptasinska
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  48. Franco Ferrario
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  49. Eduardo Gutierrez
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  50. Eva Honsova
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Corresponding author

Correspondence to Rosanna Coppo.

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Conflict of interest

We declare that the results presented in this paper have not been published previously in whole or in part.

Additional information

The authors of this article acted on behalf of the VALIGA study of the ERA-EDTA Immunonephrology Working Group.

An erratum to this article is available at http://dx.doi.org/10.1007/s00467-016-3506-2.

VALIGA Centers

VALIGA Centers

Nephrologists

V. Tesar, D. Maixnerova (Nephrology, First Faculty of Medicine and General University Hospital, Prague, Czech Republic); S. Lundberg (Nephrology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden); L. Gesualdo (Nephrology, Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Foggia-Bari, Italy); F. Emma, L. Fuiano (Nephrology, Bambino Gesù Children’s Hospital, Rome, Italy); G. Beltrame, C. Rollino (Nephrology, San Giovanni Bosco Hospital, Turin, Italy); R.Coppo, A.Amore, R.Camilla, L.Peruzzi (Nephrology, Regina Margherita Children’s Hospital, Turin, Italy); D.Lofaro, T.Papalia, R.Bonofiglio (Kidney and Transplantation Research Centre, Nephrology, Dialysis and Transplantation, Annunziata Hospital, Cosenza, Italy); M. Praga (Nephrology, Hospital 12 de Octubre, Madrid, Spain); S. Feriozzi, R. Polci, (Nephrology, Belcolle Hospital, Viterbo, Italy); L. Biancone, L.Colla (Nephrology, S. Giovanni Battista University Hospital, Turin, Italy); A. Pani, A. Angioi, D. Piras (Nephrology, G. Brotzu Hospital, Cagliari, Italy); J. Feehally (John Walls Renal Unit, Leicester General Hospital, Leicester, United Kingdom); G. Cancarini, S. Ravera (Nephrology, Spedali Civili University Hospital, Brescia, Italy); M. Durlik (Transplantation Medicine and Nephrology, Warsaw Medical University, Warsaw, Poland); E. Moggia (Nephrology, Santa Croce Hospital, Cuneo, Italy); J. Ballarin (Nephrology, Fundacion Puigvert, Barcelona, Spain); S. Di Giulio (Nephrology, San Camillo Forlanini Hospital, Rome, Italy); A.Pierucci (Nephrology, Policlinico Umberto I University Hospital, Rome, Italy); Y. Caliskan, M. Sever,(Nephrology, Internal Medicine, Istanbul Faculty of Medicine, Istanbul, Turkey); F.Locatelli, L. Del Vecchio (Nephrology, A. Manzoni Hospital, Lecco, Italy); J.F.M.Wetzels, H. Peters (Nephrology and Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands); U.Berg (Pediatrics, Department of Clinical Science, Intervention and Technology, Huddinge, Sweden); F. Carvalho, A.C. da Costa Ferreira (Nephrology, Hospital de Curry Cabral, Lisbon, Portugal); M. Maggio (Nephrology, Hospital Maggiore di Lodi, Lodi, Italy); A.Wiecek, H.Karkoszka (Nephrology, Endocrinology and Metabolic Diseases, Silesian University of Medicine, Katowice, Poland); M. Ots-Rosenberg (Nephrology, Tartu University Clinics, Tartu, Estonia); R.Magistroni (Nephrology, Policlinic of Modena and Reggio Emilia; Modena, Italy); R.Topaloglu, Y.Bilginer (Pediatric Nephrology and Rheumatology, Hacettepe University, Ankara, Turkey); M.D’Amico (Nephrology, S. Anna Hospital, Como, Italy); M.Stangou (Nephrology, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece); F.Giacchino (Nephrology, Ivrea Hospital, Ivrea, Italy); D.Goumenos, P.Kalliakmani, M.Gerolymos (Nephrology, University Hospital of Patras, Patras, Greece); K.Galesic (Nephrology, University Hospital Dubrava, Zagreb, Croatia); C.Geddes (Renal Unit, Western Infirmary Glasgow, Glasgow, United Kingdom); K.Siamopoulos, O.Balafa (Nephrology, Medical School University of Ioannina, Ioannina, Greece); M. Galliani (Nephrology, S.Pertini Hospital, Rome, Italy); P.Stratta, M.Quaglia (Nephrology, Maggiore della Carità Hospital, Piemonte Orientale University, Novara, Italy); R.Bergia, R.Cravero (Nephrolgy, Degli Infermi Hospital, Biella, Italy); M.Salvadori, L.Cirami (Nephrology, Careggi Hospital, Florence, Italy); B.Fellstrom, H.Kloster Smerud (Renal Department, University of Uppsala, Uppsala, Sweden); F. Ferrario, T. Stellato (Nephropathology, San Gerardo Hospital Monza, Italy); J. Egido, C. Martin Cleary (Nephrology, Fundacion Jimenez Diaz, Madrid, Spain); J. Floege, T. Rauen (Nephrology and Immunology, Medizinische Klinik II, University of Aachen, Aachen, Germany); A. Lupo, P. Bernich (Nephrology, University of Verona, Verona, Italy); P. Menè (Nephrology, S. Andrea Hospital, Rome, Italy); M. Morosetti (Nephrology, Grassi Hospital, Ostia, Italy); C. van Kooten, T. Rabelink, M.E.J. Reinders (Nephrology, Leiden University Medical Centre, Leiden, The Netherlands); J.M. Boria Grinyo (Nephrology, Hospital Bellvitge, Barcelona, Spain); S. Cusinato, L. Benozzi (Nephrology, Borgomanero Hospital, Borgomanero, Italy); S. Savoldi, C. Licata (Nephrology, Civile Hospital, Ciriè, Italy); M. Mizerska-Wasiak, M. Roszkowska-Blaim (Pediatrics and Nephrology, Medical University of Warsaw, Warsaw, Poland); G. Martina, A. Messuerotti (Nephrology, Chivasso Hospital, Chivasso, Italy); A. Dal Canton, C. Esposito, C. Migotto (Nephrology Units, S. Matteo Hospital and Maugeri Foundation, Pavia, Italy); G.Triolo, F.Mariano (Nephrology CTO, Turin, Italy); C.Pozzi (Nephrology, Bassini Hospital, Cinisello Balsamo, Italy); R. Boero (Nephrology, Martini Hospital, Turin, Italy)

Pathologists

G.Mazzucco (Turin, Italy); C. Giannakakis (Rome, Italy); E. Honsova (Prague, Czech Republic); B. Sundelin (Stockholm, Sweden); A.M. Di Palma (Foggia-Bari, Italy); F. Ferrario (Monza, Italy); E. Gutiérrez (Madrid, Spain); A.M. Asunis (Cagliari, Italy); J. Barratt (Leicester, United Kingdom); R. Tardanico (Brescia, Italy); A. Perkowska-Ptasinska (Warsaw, Poland); J. Arce Terroba (Barcelona, Spain); M. Fortunato (Cuneo, Italy); A. Pantzaki (Thessaloniki, Greece); Y. Ozluk, I. Kilicaslan (Istanbul, Turkey); E. Steenbergen (Nijmegen, The Netherlands); M. Soderberg (Huddinge, Sweden); Z. Riispere (Tartu, Estonia); L. Furci (Modena, Italy); D. Orhan (Ankara, Turkey); D. Kipgen (Glasgow, United Kingdom); D. Casartelli (Lecco, Italy); D. Galesic Ljubanovic (Zagreb, Croatia); H Gakiopoulou (Athens, Greece), E. Bertoni (Florence, Italy); P. Cannata Ortiz (Madrid, Spain); H. Karkoszka (Katowice, Poland), H.J. Groene (Heidelberg, Germany); A. Stoppacciaro (Rome, Italy); I. Bajema, J. Bruijn (Leiden, The Netherlands); X. Fulladosa Oliveras (Barcelona, Spain); J. Maldyk (Medical University of Warsaw, Poland); E. Ioachim (Ioannina, Greece).

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Coppo, R., Lofaro, D., Camilla, R.R. et al. Risk factors for progression in children and young adults with IgA nephropathy: an analysis of 261 cases from the VALIGA European cohort. Pediatr Nephrol 32, 139–150 (2017). https://doi.org/10.1007/s00467-016-3469-3

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  • DOI: https://doi.org/10.1007/s00467-016-3469-3

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