Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Pediatric Nephrology
Published in: Pediatric Nephrology 1/2017

01-01-2017 | Original Article

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

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 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

Published in: Pediatric Nephrology | Issue 1/2017

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
Coppo R (2008) Pediatric IgA nephropathy: clinical and therapeutic perspectives. Semin Nephrol 28:18–26CrossRefPubMed
2.
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 12:1–8CrossRefPubMed
4.
Coppo R, D’Amico G (2005) Factors predicting progression of IgA nephropathies. J Nephrol 18:503–512PubMed
5.
Haas M, Rahman MH, Cohn RA (2008) IgA nephropathy in children and adults: comparison of histologic features and clinical outcomes. Nephrol Dial Transplant 23:2537–45CrossRefPubMed
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 6:5–35CrossRef
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 28:71–76CrossRefPubMed
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 18:690–695PubMed
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 76:534–545CrossRefPubMed
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 76:546–56CrossRefPubMed
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 77:921–7CrossRefPubMed
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 27:783–92CrossRefPubMed
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 13:158CrossRefPubMedPubMedCentral
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 27:715–22CrossRefPubMed
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 27:1485–91CrossRefPubMed
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 30:2121–2127CrossRefPubMed
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 86:828–836CrossRefPubMedPubMedCentral
18.
Sleeper LA, Harrington DP (1990) Regression splines in the cox model with application to covariate effects in liver disease. J Am Stat Assoc 85:941–949CrossRef
19.
Work DF, Schwartz GJ (2008) Estimating and measuring glomerular filtration rate in children. Curr Opin Nephrol Hypertens 17:320–325CrossRefPubMed
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 130:461–470CrossRefPubMed
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 20:1995–2007CrossRefPubMed
22.
Reich HN, Troyanov S, Scholey JW, Cattran DC, Registry TG (2007) Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol 18:3177–83CrossRefPubMed
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 19:1149–56CrossRefPubMed
24.
Bou-Hamad I, Larocque D, Ben-Ameur H (2011) A review of survival trees. Stat Surv 5:44–71CrossRef
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 26:3550–65CrossRefPubMed
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 31:317–324PubMed
27.
Hastings MC, Delos Santos NM, Wyatt RJ (2007) Renal survival in pediatric patients with IgA nephropathy. Pediatr Nephrol 22:317–318CrossRefPubMed
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 21:1266–1273CrossRefPubMed
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 89:167–75CrossRefPubMed
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 12:1500–2CrossRefPubMed
Metadata
Title
Risk factors for progression in children and young adults with IgA nephropathy: an analysis of 261 cases from the VALIGA European cohort
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 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
Publication date
01-01-2017
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 1/2017
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-016-3469-3

Other articles of this Issue 1/2017

Pediatric Nephrology 1/2017 Go to the issue

Original Article

Normal values of urine total protein- and albumin-to-creatinine ratios in term newborns

Brief Report

Ofatumumab in two pediatric nephrotic syndrome patients allergic to rituximab

Original Article

Switching from immediate- to extended-release cysteamine in nephropathic cystinosis patients: a retrospective real-life single-center study

Educational Review

C3 Glomerulopathy

Original Article

Prospective study on the potential of RAAS blockade to halt renal disease in Alport syndrome patients with heterozygous mutations

Review

A holey pursuit: lumen formation in the developing kidney