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 in | Pediatric nephrology (Berlin, West) Vol. 32; no. 1; pp. 139 - 150 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
01.01.2017
Springer Nature B.V |
Subjects | |
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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 < 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 ae<yen>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. 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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D. organization: Oxford University Hospitals – sequence: 8 givenname: Licia surname: Peruzzi fullname: Peruzzi, Licia organization: Fondazione Ricerca Molinette, Nephrology, Dialysis and Transplantation, Regina Margherita Hospital – sequence: 9 givenname: Alessandro surname: Amore fullname: Amore, Alessandro organization: Fondazione Ricerca Molinette, Nephrology, Dialysis and Transplantation, Regina Margherita Hospital – sequence: 10 givenname: Francesco surname: Emma fullname: Emma, Francesco organization: Bambino Gesù Hospital – sequence: 11 givenname: Laura surname: Fuiano fullname: Fuiano, Laura organization: Bambino Gesù Hospital – sequence: 12 givenname: Ulla surname: Berg fullname: Berg, Ulla organization: Karolinska University Hospital – sequence: 13 givenname: Rezan surname: Topaloglu fullname: Topaloglu, Rezan organization: Hacettepe University – sequence: 14 givenname: Yelda surname: Bilginer fullname: Bilginer, Yelda organization: Hacettepe University – sequence: 15 givenname: Loreto surname: Gesualdo fullname: Gesualdo, Loreto organization: University of Bari and Foggia – sequence: 16 givenname: Rosaria surname: Polci fullname: Polci, Rosaria organization: Belcolle Hospital – sequence: 17 givenname: Malgorzata surname: Mizerska-Wasiak fullname: Mizerska-Wasiak, Malgorzata organization: University of Warsaw – sequence: 18 givenname: Yasar surname: Caliskan fullname: Caliskan, Yasar organization: University of Istanbul – sequence: 19 givenname: Sigrid surname: Lundberg fullname: Lundberg, Sigrid organization: Karolinska Institutet – sequence: 20 givenname: Giovanni surname: Cancarini fullname: Cancarini, Giovanni organization: Spedali Civili University Hospital – sequence: 21 givenname: Colin surname: Geddes fullname: Geddes, Colin organization: Western Infirmary Glasgow – sequence: 22 givenname: Jack surname: Wetzels fullname: Wetzels, Jack organization: Radboud University – sequence: 23 givenname: Andrzej surname: Wiecek fullname: Wiecek, Andrzej 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surname: Barratt fullname: Barratt, Jonathan organization: Leicester General Hospital – sequence: 33 givenname: Teresa surname: Papalia fullname: Papalia, Teresa organization: Annunziata Hospital – sequence: 34 givenname: Renzo surname: Bonofiglio fullname: Bonofiglio, Renzo organization: Annunziata Hospital – sequence: 35 givenname: Gianna surname: Mazzucco fullname: Mazzucco, Gianna organization: University of Turin – sequence: 36 givenname: Costantinos surname: Giannakakis fullname: Giannakakis, Costantinos organization: University of Rome – sequence: 37 givenname: Magnus surname: Soderberg fullname: Soderberg, Magnus organization: Karolinska University Hospital – sequence: 38 givenname: Diclehan surname: Orhan fullname: Orhan, Diclehan organization: Hacettepe University – sequence: 39 givenname: Anna Maria surname: Di Palma fullname: Di Palma, Anna Maria organization: University of Bari and Foggia – sequence: 40 givenname: Jadwiga surname: Maldyk fullname: Maldyk, Jadwiga organization: University of Warsaw – sequence: 41 givenname: Yasemin surname: Ozluk fullname: Ozluk, Yasemin organization: University of Istanbul – sequence: 42 givenname: Birgitta surname: Sudelin fullname: Sudelin, Birgitta organization: Karolinska Institutet – sequence: 43 givenname: Regina surname: Tardanico fullname: Tardanico, Regina organization: Spedali Civili University Hospital – sequence: 44 givenname: David surname: Kipgen fullname: Kipgen, David organization: Western Infirmary Glasgow – sequence: 45 givenname: Eric surname: Steenbergen fullname: Steenbergen, Eric organization: Radboud University – sequence: 46 givenname: Henryk surname: Karkoszka fullname: Karkoszka, Henryk organization: Silesian University – sequence: 47 givenname: Agnieszka surname: Perkowska-Ptasinska fullname: Perkowska-Ptasinska, Agnieszka organization: Warsaw Medical University – sequence: 48 givenname: Franco surname: Ferrario fullname: Ferrario, Franco organization: Monza Hospital – sequence: 49 givenname: Eduardo surname: Gutierrez fullname: Gutierrez, Eduardo organization: Hospital 12 de Octubre – sequence: 50 givenname: Eva surname: Honsova fullname: Honsova, Eva organization: General University Hospital |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27557557$$D View this record in MEDLINE/PubMed https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-312033$$DView record from Swedish Publication Index http://kipublications.ki.se/Default.aspx?queryparsed=id:134726861$$DView record from Swedish Publication Index |
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ContentType | Journal Article |
Copyright | IPNA 2016 Pediatric Nephrology is a copyright of Springer, 2017. |
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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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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 |
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