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Pediatric Nephrology

, Volume 32, Issue 1, pp 139–150 | Cite as

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

  • Rosanna CoppoEmail author
  • Danilo Lofaro
  • Roberta R Camilla
  • Shubha Bellur
  • Daniel Cattran
  • H. Terence Cook
  • Ian S. D. Roberts
  • Licia Peruzzi
  • Alessandro Amore
  • Francesco Emma
  • Laura Fuiano
  • Ulla Berg
  • Rezan Topaloglu
  • Yelda. Bilginer
  • Loreto Gesualdo
  • Rosaria Polci
  • Malgorzata Mizerska-Wasiak
  • Yasar Caliskan
  • Sigrid Lundberg
  • Giovanni Cancarini
  • Colin Geddes
  • Jack Wetzels
  • Andrzej Wiecek
  • Magdalena Durlik
  • Stefano Cusinato
  • Cristiana Rollino
  • Milena Maggio
  • Manuel Praga
  • Hilde K.Smerud
  • Vladimir Tesar
  • Dita Maixnerova
  • Jonathan Barratt
  • Teresa Papalia
  • Renzo Bonofiglio
  • Gianna Mazzucco
  • Costantinos Giannakakis
  • Magnus Soderberg
  • Diclehan Orhan
  • Anna Maria Di Palma
  • Jadwiga Maldyk
  • Yasemin Ozluk
  • Birgitta Sudelin
  • Regina Tardanico
  • David Kipgen
  • Eric Steenbergen
  • Henryk Karkoszka
  • Agnieszka Perkowska-Ptasinska
  • Franco Ferrario
  • Eduardo Gutierrez
  • Eva Honsova
Original Article

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.

Keywords

IgA nephropathy Progression Pathology classification Proteinuria Risk factors 

Notes

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.

Compliance with ethical standards

Conflict of interest

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

References

  1. 1.
    Coppo R (2008) Pediatric IgA nephropathy: clinical and therapeutic perspectives. Semin Nephrol 28:18–26CrossRefPubMedGoogle Scholar
  2. 2.
    Wyatt RJ, Julian BA (2013) IgA nephropathy. N Engl J Med 368:2402–2414CrossRefPubMedGoogle Scholar
  3. 3.
    Yamagata K, Iseki K, Nitta K, Imai H, Iino Y, Matsuo S, Makino H, Hishida A (2008) Chronic kidney disease perspectives in Japan and the importance of urinalysis screening. Clin Exp Nephrol 12:1–8CrossRefPubMedGoogle Scholar
  4. 4.
    Coppo R, D’Amico G (2005) Factors predicting progression of IgA nephropathies. J Nephrol 18:503–512PubMedGoogle Scholar
  5. 5.
    Haas M, Rahman MH, Cohn RA (2008) IgA nephropathy in children and adults: comparison of histologic features and clinical outcomes. Nephrol Dial Transplant 23:2537–45CrossRefPubMedGoogle Scholar
  6. 6.
    Fassbinder W, Brunner FP, Brynger H, Ehrich JH, Geerlings W, Raine AE, Rizzoni G, Selwood NH, Tufveson G, Wing AJ (1991) Combined report on regular dialysis and transplantation in Europe. Nephrol Dial Transplant 6:5–35CrossRefGoogle Scholar
  7. 7.
    Shima Y, Nakanishi K, Hama T, Mukaiyama H, Togawa H, Sako M, Kaito H, Nozu K, Tanaka R, Iijima K, Yoshikawa N (2013) Spontaneous remission in children with IgA nephropathy. Pediatr Nephrol 28:71–76CrossRefPubMedGoogle Scholar
  8. 8.
    Komatsu H, Fujimoto S, Sato Y, Hara S, Yamada K, Morita S, Eto T (2005) “Point of no return (PNR)” in progressive IgA nephropathy: significance of blood pressure and proteinuria management up to PNR. J Nephrol 18:690–695PubMedGoogle Scholar
  9. 9.
    Cattran DC, Coppo R, Cook HT, Feehally J, Roberts IS, Troyanov S, Alpers CE, Amore A, Barratt J, Berthoux F, Bonsib S, Bruijn JA, D’Agati V, D’Amico G, Emancipator S, Emma F, Ferrario F, Fervenza FC, Florquin S, Fogo A, Geddes CC, Groene HJ, Haas M, Herzenberg AM, Hill PA, Hogg RJ, Hsu SI, Jennette JC, Joh K, Julian BA, Kawamura T, Lai FM, Leung CB, Li LS, Li PK, Liu ZH, Mackinnon B, Mezzano S, Schena FP, Tomino Y, Walker PD, Wang H, Weening JJ, Yoshikawa N, Zhang H (2009) The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int 76:534–545CrossRefPubMedGoogle Scholar
  10. 10.
    Roberts IS, Cook HT, Troyanov S, Alpers CE, Amore A, Barratt J, Berthoux F, Bonsib S, Bruijn JA, Cattran DC, Coppo R, D’Agati V, D’Amico G, Emancipator S, Emma F, Feehally J, Ferrario F, Fervenza FC, Florquin S, Fogo A, Geddes CC, Groene HJ, Haas M, Herzenberg AM, Hill PA, Hogg RJ, Hsu SI, Jennette JC, Joh K, Julian BA, Kawamura T, Lai FM, Li LS, Li PK, Liu ZH, Mackinnon B, Mezzano S, Schena FP, Tomino Y, Walker PD, Wang H, Weening JJ, Yoshikawa N, Zhang H (2009) The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int 76:546–56CrossRefPubMedGoogle Scholar
  11. 11.
    Coppo R, Troyanov S, Camilla R, Hogg RJ, Cattran DC, Cook HT, Feehally J, Roberts IS, Amore A, Alpers CE, Barratt J, Berthoux F, Bonsib S, Bruijn JA, D’Agati V, D’Amico G, Emancipator SN, Emma F, Ferrario F, Fervenza FC, Florquin S, Fogo AB, Geddes CC, Groene HJ, Haas M, Herzenberg AM, Hill PA, Hsu SI, Jennette JC, Joh K, Julian BA, Kawamura T, Lai FM, Li LS, Li PK, Liu ZH, Mezzano S, Schena FP, Tomino Y, Walker PD, Wang H, Weening JJ, Yoshikawa N, Zhang H (2010) The Oxford IgA nephropathy clinicopathological classification is valid for children as well as adults. Kidney Int 77:921–7CrossRefPubMedGoogle Scholar
  12. 12.
    Shima Y, Nakanishi K, Hama T, Mukaiyama H, Togawa H, Hashimura Y, Kaito H, Sako M, Iijima K, Yoshikawa N (2012) Validity of the Oxford classification of IgA nephropathy in children. Pediatr Nephrol 27:783–92CrossRefPubMedGoogle Scholar
  13. 13.
    Le W, Zeng CH, Liu Z, Liu D, Yang Q, Lin RX, Xia ZK, Fan ZM, Zhu G, Wu Y, Xu H, Zhai Y, Ding Y, Yang X, Liang S, Chen H, Xu F, Huang Q, Shen H, Wang J, Fogo AB, Liu ZH (2012) Validation of the Oxford classification of IgA nephropathy for pediatric patients from China. BMC Nephrol 13:158CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Edström Halling S, Söderberg MP, Berg UB (2012) Predictors of outcome in paediatric IgA nephropathy with regard to clinical and histopathological variables (Oxford classification). Nephrol Dial Transplant 27:715–22CrossRefPubMedGoogle Scholar
  15. 15.
    Bjørneklett R, Vikse BE, Bostad L, Leivestad T, Iversen BM (2011) Long-term risk of ESRD in IgAN; validation of Japanese prognostic model in a Norwegian cohort. Nephrol Dial Transplant 27:1485–91CrossRefPubMedGoogle Scholar
  16. 16.
    Higa A, Shima Y, Hama T, Sato M, Mukaiyama H, Togawa H, Tanaka R, Nozu K, Sako M, Iijima K, Nakanishi K, Yoshikawa N (2015) Long-term outcome of childhood IgA nephropathy with minimal proteinuria. Pediatr Nephrol 30:2121–2127CrossRefPubMedGoogle Scholar
  17. 17.
    Coppo R, Troyanov S, Bellur S, Cattran D, Cook HT, Feehally J, Roberts IS, Morando L, Camilla R, Tesar V, Lunberg S, Gesualdo L, Emma F, Rollino C, Amore A, Praga M, Feriozzi S, Segoloni G, Pani A, Cancarini G, Durlik M, Moggia E, Mazzucco G, Giannakakis C, Honsova E, Sundelin BB, Di Palma AM, Ferrario F, Gutierrez E, Asunis AM, Barratt J, Tardanico R, Perkowska-Ptasinska A, VALIGA study of the ERA-EDTA Immunonephrology Working Group, (2014) Validation of the Oxford classification of IgA nephropathy in cohorts with different presentations and treatments. Kidney Int 86:828–836CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Sleeper LA, Harrington DP (1990) Regression splines in the cox model with application to covariate effects in liver disease. J Am Stat Assoc 85:941–949CrossRefGoogle Scholar
  19. 19.
    Work DF, Schwartz GJ (2008) Estimating and measuring glomerular filtration rate in children. Curr Opin Nephrol Hypertens 17:320–325CrossRefPubMedGoogle Scholar
  20. 20.
    Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130:461–470CrossRefPubMedGoogle Scholar
  21. 21.
    Wühl E, Witte K, Soergel M, Mehls O, Schaefer F (2002) Distribution of 24-h ambulatory blood pressure in children: normalized reference values and role of body dimensions. J Hypertens 20:1995–2007CrossRefPubMedGoogle Scholar
  22. 22.
    Reich HN, Troyanov S, Scholey JW, Cattran DC, Registry TG (2007) Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol 18:3177–83CrossRefPubMedGoogle Scholar
  23. 23.
    Matsushita S, Ishikura K, Okamoto S, Okuda Y, Nagaoka Y, Harada R, Hamada R, Sakai T, Hamasaki Y, Hataya H, Ando T, Ogata K, Honda M (2015) Long-term morbidity of IgA nephropathy in children evaluated with newly proposed remission criteria in Japan. Clin Exp Nephrol 19:1149–56CrossRefPubMedGoogle Scholar
  24. 24.
    Bou-Hamad I, Larocque D, Ben-Ameur H (2011) A review of survival trees. Stat Surv 5:44–71CrossRefGoogle Scholar
  25. 25.
    Austin PC (2007) A comparison of the statistical power of different methods for the analysis of cluster randomization trials with binary outcomes. Stat Med 26:3550–65CrossRefPubMedGoogle Scholar
  26. 26.
    Lofaro D, Jager KJ, Abu-Hanna A, Groothoff JW, Arikoski P, Hoecker B, Roussey-Kesler G, Spasojević B, Verrina E, Schaefer F, van Stralen KJ, ESPN/ERA-EDTA Registry (2015) Identification of subgroups by risk of graft failure after paediatric renal transplantation: application of survival tree models on the ESPN/ERA-EDTA Registry. Nephrol Dial Transplant 31:317–324PubMedGoogle Scholar
  27. 27.
    Hastings MC, Delos Santos NM, Wyatt RJ (2007) Renal survival in pediatric patients with IgA nephropathy. Pediatr Nephrol 22:317–318CrossRefPubMedGoogle Scholar
  28. 28.
    Ronkainen J, Ala-Houhala M, Autio-Harainen H, Jahnukainen T, Koskimies O, Merenmies J, Mustonen J, Ormälä T, Turtinen J, Nuutinen M (2006) Long-term outcome 19 years after childhood IgA nephritis: a retrospective cohort study. Pediatr Nephrol 21:1266–1273CrossRefPubMedGoogle Scholar
  29. 29.
    Barbour SJ, Espino-Hernandez G, Reich HN, Coppo R, Roberts IS, Feehally J, Herzenberg AM, Cattran DC, VALIGA; OXFORD DERIVATION AND NORTH AMERICAN VALIDATION (2016) The MEST score provides earlier risk prediction in IgA nephropathy. Kidney Int 89:167–75CrossRefPubMedGoogle Scholar
  30. 30.
    Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, Poole C, Schlesselman JJ, Egger M, Initiative STROBE (2014) Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. Int J Surg 12:1500–2CrossRefPubMedGoogle Scholar

Copyright information

© IPNA 2016

Authors and Affiliations

  • Rosanna Coppo
    • 1
    Email author
  • Danilo Lofaro
    • 2
  • Roberta R Camilla
    • 1
  • Shubha Bellur
    • 3
  • Daniel Cattran
    • 4
  • H. Terence Cook
    • 5
  • Ian S. D. Roberts
    • 3
  • Licia Peruzzi
    • 1
  • Alessandro Amore
    • 1
  • Francesco Emma
    • 6
  • Laura Fuiano
    • 6
  • Ulla Berg
    • 7
  • Rezan Topaloglu
    • 8
  • Yelda. Bilginer
    • 8
  • Loreto Gesualdo
    • 9
  • Rosaria Polci
    • 10
  • Malgorzata Mizerska-Wasiak
    • 11
  • Yasar Caliskan
    • 12
  • Sigrid Lundberg
    • 13
  • Giovanni Cancarini
    • 14
  • Colin Geddes
    • 15
  • Jack Wetzels
    • 16
  • Andrzej Wiecek
    • 17
  • Magdalena Durlik
    • 18
  • Stefano Cusinato
    • 19
  • Cristiana Rollino
    • 20
  • Milena Maggio
    • 21
  • Manuel Praga
    • 22
  • Hilde K.Smerud
    • 23
  • Vladimir Tesar
    • 24
  • Dita Maixnerova
    • 24
  • Jonathan Barratt
    • 25
  • Teresa Papalia
    • 2
  • Renzo Bonofiglio
    • 2
  • Gianna Mazzucco
    • 26
  • Costantinos Giannakakis
    • 27
  • Magnus Soderberg
    • 7
  • Diclehan Orhan
    • 8
  • Anna Maria Di Palma
    • 9
  • Jadwiga Maldyk
    • 11
  • Yasemin Ozluk
    • 12
  • Birgitta Sudelin
    • 13
  • Regina Tardanico
    • 14
  • David Kipgen
    • 15
  • Eric Steenbergen
    • 16
  • Henryk Karkoszka
    • 17
  • Agnieszka Perkowska-Ptasinska
    • 18
  • Franco Ferrario
    • 28
  • Eduardo Gutierrez
    • 22
  • Eva Honsova
    • 24
  1. 1.Fondazione Ricerca Molinette, Nephrology, Dialysis and TransplantationRegina Margherita HospitalTurinItaly
  2. 2.Annunziata HospitalCosenzaItaly
  3. 3.Oxford University HospitalsOxfordUK
  4. 4.Toronto General HospitalUniversity Health NetworkTorontoCanada
  5. 5.Imperial CollegeHammersmith HospitalLondonUK
  6. 6.Bambino Gesù HospitalRomeItaly
  7. 7.Karolinska University HospitalHuddingeSweden
  8. 8.Hacettepe UniversityAnkaraTurkey
  9. 9.University of Bari and FoggiaBariItaly
  10. 10.Belcolle HospitalViterboItaly
  11. 11.University of WarsawWarsawPoland
  12. 12.University of IstanbulIstanbulTurkey
  13. 13.Karolinska InstitutetStockholmSweden
  14. 14.Spedali Civili University HospitalBresciaItaly
  15. 15.Western Infirmary GlasgowGlasgowUK
  16. 16.Radboud UniversityNijmegenThe Netherlands
  17. 17.Silesian UniversityKatowicePoland
  18. 18.Warsaw Medical UniversityWarsawPoland
  19. 19.Borgomanero HospitalBorgomaneroItaly
  20. 20.San Giovanni Bosco HospitalTurinItaly
  21. 21.Hospital Maggiore di LodiLodiItaly
  22. 22.Hospital 12 de OctubreMadridSpain
  23. 23.University of UppsalaUppsalaSweden
  24. 24.General University HospitalPragueCzech Republic
  25. 25.Leicester General HospitalLeicesterUK
  26. 26.University of TurinTurinItaly
  27. 27.University of RomeRomeItaly
  28. 28.Monza HospitalMonzaItaly

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