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NAG and β2M as biomarkers of steroid resistance in children with idiopathic nephrotic syndrome : a systematic review and meta-analysis
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Introdução: A síndrome nefrótica resistente a corticosteroides (SNRC) é a segunda causa mais comum de doença renal crónica nas primeiras três décadas de vida. Quase 20% das crianças com síndrome nefrótica idiopática (SNI) terão SNRC. Biomarcadores não invasivos poderão ser úteis para prever a resposta aos corticosteroides e individualizar o tratamento de crianças com SNI, levando a melhores cuidados e resultados mais favoráveis.
Objetivos: Avaliar os biomarcadores N-acetil-β-glicosaminidase (NAG) e β2-microglobulina urinária (β2M) como preditores de resposta a corticosteroides em crianças com SNI.
Métodos: Foi realizada uma revisão sistemática com meta-análise, tendo sido incluídos dados de estudos pediátricos, nos quais os biomarcadores urinários NAG, β2M ou ambos tenham sido medidos no início do SNI. Os estudos foram identificados através de uma pesquisa no MEDLINE e no EMBASE, até dezembro de 2017. Dois autores avaliaram independentemente estudos para inclusão e risco de viés e selecionaram os dados. Os valores médios de NAG e β2M (correspondentes ao início do SNI) foram comparados entre os grupos definidos de acordo com a resposta subsequente aos corticosteroides (SNSC ou SNRC).
Resultados: Dois estudos (69 pacientes) foram incluídos. O risco global de viés entre os estudos foi considerado moderado. Comparando pacientes com SNSC àqueles com SNRC, a diferença padronizada da média para o NAG urinário foi de -0,57 (intervalo de confiança de 95%, -0,83 a -0,32; valor de P <0,002) e -0,42 para o β2M urinário (95% de confiança intervalo, -0,77 a -0,07, valor de P <0,002).
Conclusões: Os biomarcadores urinários NAG e o β2M podem ajudar a prever a resposta a corticosteroides em crianças com SNI. No entanto, apenas dois estudos preencheram os critérios definidos. São necessários mais estudos que abordem o ponto de corte ideal do NAG e β2M para esclarecer a utilidade da sua medição na prática clínica.
Background: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of chronic kidney disease in the first three decades of life. Nearly 20% of children presenting with idiopathic nephrotic syndrome (INS) will have SRNS. Noninvasive biomarkers to predict steroid response may be helpful to individualize treatment of children with INS, potentially leading to better care and more favorable outcomes. Objectives: To evaluate urinary N-acetyl-β-glucosaminidase (NAG) and β2-microglobulin (β2M) as predictors of steroid response in children presenting with INS. Methods: We conducted a systematic review with meta-analysis including data from pediatric studies in which urinary NAG, β2M, or both biomarkers were measured at onset of INS. Studies were identified by searching the MEDLINE and EMBASE up to December 2017. Two reviewers independently assessed studies for inclusion and risk of bias and extracted the data. We compared mean NAG and mean β2M at onset of INS between groups defined according to subsequent response to steroids (SSNS or SRNS). Results: Two studies (69 patients) were included. The overall risk of bias across studies was considered moderate. Comparing patients with SSNS to those with SRNS, the estimate of the population standardized mean differences in urinary NAG was -0.57 (95% confidence interval, -0.83 to -0.32; P value <0.002) and -0.42 in urinary β2M (95% confidence interval, -0.77 to -0.07; P value <0.002). Conclusions: Our results suggest that urinary NAG and β2M may help to predict response to steroids in children presenting with INS. Nevertheless, only two studies fulfilled the defined criteria and were included in this review. Further studies addressing the ideal cut off point of urinary NAG and β2M to predict steroid responsiveness are needed to clarify the utility of measuring these biomarkers in the clinical setting.
Background: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of chronic kidney disease in the first three decades of life. Nearly 20% of children presenting with idiopathic nephrotic syndrome (INS) will have SRNS. Noninvasive biomarkers to predict steroid response may be helpful to individualize treatment of children with INS, potentially leading to better care and more favorable outcomes. Objectives: To evaluate urinary N-acetyl-β-glucosaminidase (NAG) and β2-microglobulin (β2M) as predictors of steroid response in children presenting with INS. Methods: We conducted a systematic review with meta-analysis including data from pediatric studies in which urinary NAG, β2M, or both biomarkers were measured at onset of INS. Studies were identified by searching the MEDLINE and EMBASE up to December 2017. Two reviewers independently assessed studies for inclusion and risk of bias and extracted the data. We compared mean NAG and mean β2M at onset of INS between groups defined according to subsequent response to steroids (SSNS or SRNS). Results: Two studies (69 patients) were included. The overall risk of bias across studies was considered moderate. Comparing patients with SSNS to those with SRNS, the estimate of the population standardized mean differences in urinary NAG was -0.57 (95% confidence interval, -0.83 to -0.32; P value <0.002) and -0.42 in urinary β2M (95% confidence interval, -0.77 to -0.07; P value <0.002). Conclusions: Our results suggest that urinary NAG and β2M may help to predict response to steroids in children presenting with INS. Nevertheless, only two studies fulfilled the defined criteria and were included in this review. Further studies addressing the ideal cut off point of urinary NAG and β2M to predict steroid responsiveness are needed to clarify the utility of measuring these biomarkers in the clinical setting.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2018
Palavras-chave
Síndrome nefrótica Corticosteroides N-acetil-β-glucosaminidase β2-microglobulina Fisiopatologia