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

• DOI: 10.1007/s00467-016-3469-3
• Publication Date: 2016-08-24T23:11:11Z
• Authors: Rosanna Coppo; 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 Mizers...; 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 Giann...; Magnus Soderberg; Diclehan Orhan; Anna Maria Di Palma; Jadwiga Maldyk; Yasemin Ozluk; Birgitta Sudelin; Regina Tardanico; David Kipgen; Eric Steenbergen; Henryk Karkoszka; Agnieszka Perkows...; Franco Ferrario; Eduardo Gutierrez; Eva Honsova
• Keywords: Male; Endpoint Determination; Biopsy; 610; IgA nephropathy; pathology classification; progression; proteinuria; risk factors; pediatrics; perinatology and child health; nephrology; Kidney; Pediatrics; Cohort Studies; 03 medical and health sciences; 0302 clinical medicine; Adrenal Cortex Hormones; 1114 Paediatrics And Reproductive Medicine; Humans; Child; Retrospective Studies; Radboudumc 11: Renal disorders RIHS: Radboud Institute for Health Sciences; IgA nephropathy; Pathology classification; Progression; Proteinuria; Risk factors; Science & Technology; Progression; Pathology - Radboud University Medical Center; Age Factors; Pathology classification; Infant; 600; Glomerulonephritis, IGA; IgA nephropathy; Perinatology and Child Health; Urology & Nephrology; Radboudumc 11: Renal disorders RIMLS: Radboud Institute for Molecular Life Sciences; 3. Good health; Europe; Proteinuria; Risk factors; Nephrology; Child, Preschool; IgA nephropathy; Pathology classification; Progression; Proteinuria; Risk factors; Pediatrics, Perinatology and Child Health; Nephrology; Disease Progression; Kidney Failure, Chronic; Female; Risk factor; Life Sciences & Biomedicine; Immunosuppressive Agents; Glomerular Filtration Rate

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