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

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 O...

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Published inPediatric nephrology (Berlin, West) Vol. 32; no. 1; pp. 139 - 150
Main Authors Coppo, Rosanna, Lofaro, Danilo, Camilla, Roberta R, Bellur, Shubha, Cattran, Daniel, Cook, H. Terence, Roberts, Ian S. D., Peruzzi, Licia, Amore, Alessandro, Emma, Francesco, Fuiano, Laura, Berg, Ulla, Topaloglu, Rezan, Bilginer, Yelda, Gesualdo, Loreto, Polci, Rosaria, Mizerska-Wasiak, Malgorzata, Caliskan, Yasar, Lundberg, Sigrid, Cancarini, Giovanni, Geddes, Colin, Wetzels, Jack, Wiecek, Andrzej, Durlik, Magdalena, Cusinato, Stefano, Rollino, Cristiana, Maggio, Milena, Praga, Manuel, K.Smerud, Hilde, Tesar, Vladimir, Maixnerova, Dita, Barratt, Jonathan, Papalia, Teresa, Bonofiglio, Renzo, Mazzucco, Gianna, Giannakakis, Costantinos, Soderberg, Magnus, Orhan, Diclehan, Di Palma, Anna Maria, Maldyk, Jadwiga, Ozluk, Yasemin, Sudelin, Birgitta, Tardanico, Regina, Kipgen, David, Steenbergen, Eric, Karkoszka, Henryk, Perkowska-Ptasinska, Agnieszka, Ferrario, Franco, Gutierrez, Eduardo, Honsova, Eva
Format Journal Article
LanguageEnglish
Published Berlin/Heidelberg Springer Berlin Heidelberg 01.01.2017
Springer Nature B.V
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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 m 2 and an eGFR of <90 ml/min/1.73 m 2 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 m 2 ) 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.
AbstractList 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 &lt; 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 &lt; 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 &lt; 18 years. The regression tree classification indicated that patients with M1 were at risk of developing higher time-averaged proteinuria (p &lt; 0.0001) and the combined endpoint (p &lt; 0.001). An initial proteinuria of ae&lt;yen&gt;0.4 g/day/1.73 m(2) and an eGFR of &lt; 90 ml/min/1.73 m(2) were determined to be risk factors in subjects with M0. Children aged &lt; 16 years with M0 and well-preserved eGFR (&gt; 90 ml/min/1.73 m(2)) 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.
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 greater than or equal to 0.4 g/day/1.73 m super(2) and an eGFR of <90 ml/min/1.73 m super(2) 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 m super(2) ) 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.
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 m 2 and an eGFR of <90 ml/min/1.73 m 2 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 m 2 ) 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.
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 m and an eGFR of <90 ml/min/1.73 m 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 m ) 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.
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 [greater than or equal to]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.
There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease.BACKGROUNDThere 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.METHODSData 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.RESULTSIn 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.CONCLUSIONThis new statistical approach has identified clinical and histological risk factors associated with outcome in children and young adults with IgAN.
Author Tesar, Vladimir
Mizerska-Wasiak, Malgorzata
Emma, Francesco
Wetzels, Jack
Papalia, Teresa
Maldyk, Jadwiga
Rollino, Cristiana
Lundberg, Sigrid
Wiecek, Andrzej
Giannakakis, Costantinos
Maixnerova, Dita
Topaloglu, Rezan
Bonofiglio, Renzo
Maggio, Milena
Steenbergen, Eric
Caliskan, Yasar
Di Palma, Anna Maria
Bilginer, Yelda
Sudelin, Birgitta
Cook, H. Terence
Orhan, Diclehan
Karkoszka, Henryk
Camilla, Roberta R
Amore, Alessandro
Fuiano, Laura
Cusinato, Stefano
Ferrario, Franco
Bellur, Shubha
Geddes, Colin
Coppo, Rosanna
Tardanico, Regina
Roberts, Ian S. D.
K.Smerud, Hilde
Gutierrez, Eduardo
Honsova, Eva
Cattran, Daniel
Ozluk, Yasemin
Barratt, Jonathan
Lofaro, Danilo
Polci, Rosaria
Berg, Ulla
Cancarini, Giovanni
Praga, Manuel
Gesualdo, Loreto
Kipgen, David
Mazzucco, Gianna
Perkowska-Ptasinska, Agnieszka
Durlik, Magdalena
Soderberg, Magnus
Peruzzi, Licia
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http://kipublications.ki.se/Default.aspx?queryparsed=id:134726861$$DView record from Swedish Publication Index
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IgA nephropathy
Pathology classification
Risk factors
Proteinuria
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PublicationSubtitle Journal of the International Pediatric Nephrology Association
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References_xml – volume: 26
  start-page: 3550
  year: 2007
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Snippet Background There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease. Methods Data...
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...
Background There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease. Methods Data...
There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease.BACKGROUNDThere is a...
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...
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pubmed
crossref
springer
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Enrichment Source
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StartPage 139
SubjectTerms Adrenal Cortex Hormones - therapeutic use
Age Factors
Biopsy
Child
Child, Preschool
Classification
Cohort Studies
Disease Progression
Endpoint Determination
Europe - epidemiology
Female
Glomerular Filtration Rate
Glomerulonephritis, IGA - drug therapy
Glomerulonephritis, IGA - epidemiology
Glomerulonephritis, IGA - pathology
Humans
IgA nephropathy
Immunosuppressive Agents
Infant
Kidney - pathology
Kidney diseases
Kidney Failure, Chronic - epidemiology
Kidney Failure, Chronic - pathology
Male
Medicine
Medicine & Public Health
Nephrology
Original Article
Pathology
Pathology classification
Pediatrics
Progression
Proteinuria
Proteinuria - epidemiology
Proteinuria - pathology
Remission (Medicine)
Retrospective Studies
Risk Factors
Sex Factors
Survival Analysis
Urology
Young adults
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Title Risk factors for progression in children and young adults with IgA nephropathy: an analysis of 261 cases from the VALIGA European cohort
URI https://link.springer.com/article/10.1007/s00467-016-3469-3
https://www.ncbi.nlm.nih.gov/pubmed/27557557
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