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1.
Pediatr Nephrol ; 32(1): 139-150, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27557557

RESUMO

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.


Assuntos
Glomerulonefrite por IGA/epidemiologia , Corticosteroides/uso terapêutico , Fatores Etários , Biópsia , Criança , Pré-Escolar , Estudos de Coortes , Progressão da Doença , Determinação de Ponto Final , Europa (Continente)/epidemiologia , Feminino , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/patologia , Humanos , Imunossupressores , Lactente , Rim/patologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/patologia , Masculino , Proteinúria/epidemiologia , Proteinúria/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Análise de Sobrevida
3.
Kidney Int ; 86(4): 828-36, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24694989

RESUMO

The Oxford Classification of IgA Nephropathy (IgAN) identified mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) as independent predictors of outcome. Whether it applies to individuals excluded from the original study and how therapy influences the predictive value of pathology remain uncertain. The VALIGA study examined 1147 patients from 13 European countries that encompassed the whole spectrum of IgAN. Over a median follow-up of 4.7 years, 86% received renin-angiotensin system blockade and 42% glucocorticoid/immunosuppressive drugs. M, S, and T lesions independently predicted the loss of estimated glomerular filtration rate (eGFR) and a lower renal survival. Their value was also assessed in patients not represented in the Oxford cohort. In individuals with eGFR less than 30 ml/min per 1.73 m(2), the M and T lesions independently predicted a poor survival. In those with proteinuria under 0.5 g/day, both M and E lesions were associated with a rise in proteinuria to 1 or 2 g/day or more. The addition of M, S, and T lesions to clinical variables significantly enhanced the ability to predict progression only in those who did not receive immunosuppression (net reclassification index 11.5%). The VALIGA study provides a validation of the Oxford classification in a large European cohort of IgAN patients across the whole spectrum of the disease. The independent predictive value of pathology MEST score is reduced by glucocorticoid/immunosuppressive therapy.


Assuntos
Glomerulonefrite por IGA/classificação , Glomerulonefrite por IGA/patologia , Falência Renal Crônica/patologia , Rim/patologia , Adolescente , Adulto , Atrofia , Criança , Progressão da Doença , Europa (Continente) , Feminino , Fibrose , Seguimentos , Taxa de Filtração Glomerular , Mesângio Glomerular/patologia , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Imunossupressores/uso terapêutico , Rim/irrigação sanguínea , Falência Renal Crônica/fisiopatologia , Túbulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/patologia , Valor Preditivo dos Testes , Proteinúria/patologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Estudos Retrospectivos , Adulto Jovem
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