title: Risk factors for progression in children and young adults with IgA nephropathy: an analysis of 261 cases from the VALIGA European cohort.
abstract: There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease.
  
  
  
  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.
  
  
  
  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 m2and an eGFR of <90 ml/min/1.73 m2were 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.
  
  
  
  This new statistical approach has identified clinical and histological risk factors associated with outcome in children and young adults with IgAN.
authors.affiliation: Fondazione Ricerca Molinette, Nephrology, Dialysis and Transplantation, Regina Margherita Hospital, Turin, Italy. rosanna.coppo@unito.it.
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authors.lastname: Coppo
authors.affiliation: Annunziata Hospital, Cosenza, Italy.
authors.forename: Danilo
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authors.lastname: Lofaro
authors.affiliation: Fondazione Ricerca Molinette, Nephrology, Dialysis and Transplantation, Regina Margherita Hospital, Turin, Italy.
authors.forename: Roberta R
authors.initials: RR
authors.lastname: Camilla
authors.affiliation: Oxford University Hospitals, Oxford, UK.
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authors.affiliation: Toronto General Hospital, University Health Network, Toronto, Canada.
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authors.affiliation: Oxford University Hospitals, Oxford, UK.
authors.forename: Ian S D
authors.initials: IS
authors.lastname: Roberts
authors.affiliation: Fondazione Ricerca Molinette, Nephrology, Dialysis and Transplantation, Regina Margherita Hospital, Turin, Italy.
authors.forename: Licia
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authors.lastname: Peruzzi
authors.affiliation: Fondazione Ricerca Molinette, Nephrology, Dialysis and Transplantation, Regina Margherita Hospital, Turin, Italy.
authors.forename: Alessandro
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authors.affiliation: Bambino Gesù Hospital, Rome, Italy.
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authors.forename: Ulla
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authors.affiliation: Hacettepe University, Ankara, Turkey.
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authors.forename: Yelda
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authors.lastname: Bilginer
authors.affiliation: University of Bari and Foggia, Bari, Italy.
authors.forename: Loreto
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authors.lastname: Gesualdo
authors.affiliation: Belcolle Hospital, Viterbo, Italy.
authors.forename: Rosaria
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authors.lastname: Polci
authors.affiliation: University of Warsaw, Warsaw, Poland.
authors.forename: Malgorzata
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authors.affiliation: University of Istanbul, Istanbul, Turkey.
authors.forename: Yasar
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authors.forename: Sigrid
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authors.lastname: Lundberg
authors.affiliation: Spedali Civili University Hospital, Brescia, Italy.
authors.forename: Giovanni
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authors.forename: Jack
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authors.lastname: Wetzels
authors.affiliation: Silesian University, Katowice, Poland.
authors.forename: Andrzej
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authors.affiliation: Warsaw Medical University, Warsaw, Poland.
authors.forename: Magdalena
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authors.lastname: Durlik
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authors.affiliation: San Giovanni Bosco Hospital, Turin, Italy.
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authors.lastname: Maggio
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authors.lastname: Praga
authors.affiliation: University of Uppsala, Uppsala, Sweden.
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authors.forename: Gianna
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authors.lastname: Mazzucco
authors.affiliation: University of Rome, Rome, Italy.
authors.forename: Costantinos
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authors.affiliation: Karolinska University Hospital, Huddinge, Sweden.
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authors.affiliation: Hacettepe University, Ankara, Turkey.
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authors.affiliation: University of Bari and Foggia, Bari, Italy.
authors.forename: Anna Maria
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authors.lastname: Di Palma
authors.affiliation: University of Warsaw, Warsaw, Poland.
authors.forename: Jadwiga
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authors.lastname: Maldyk
authors.affiliation: University of Istanbul, Istanbul, Turkey.
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authors.lastname: Ozluk
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authors.forename: Birgitta
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authors.affiliation: Spedali Civili University Hospital, Brescia, Italy.
authors.forename: Regina
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authors.affiliation: Western Infirmary Glasgow, Glasgow, UK.
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authors.lastname: Kipgen
authors.affiliation: Radboud University, Nijmegen, The Netherlands.
authors.forename: Eric
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authors.lastname: Steenbergen
authors.affiliation: Silesian University, Katowice, Poland.
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authors.lastname: Karkoszka
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authors.forename: Agnieszka
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authors.lastname: Perkowska-Ptasinska
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authors.affiliation: Hospital 12 de Octubre, Madrid, Spain.
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mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000367:Age Factors; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D023381:Endpoint Determination; D005060:Europe / Q000453:epidemiology; D005260:Female; D005919:Glomerular Filtration Rate; D005922:Glomerulonephritis, IGA / Q000188:drug therapy / Q000453:epidemiology* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents; D007223:Infant; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000473:pathology; D008297:Male; D011507:Proteinuria / Q000453:epidemiology / Q000473:pathology; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D016019:Survival Analysis
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents
keywords: IgA nephropathy; Pathology classification; Progression; Proteinuria; Risk factors