Análise de biomarcadores renais em pacientes com doença de Fabry
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Data
2018-02-26
Autores
Braga, Marion Coting [UNIFESP]
Orientadores
D'Almeida, Vania [UNIFESP]
Tipo
Dissertação de mestrado
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Introdução: Recomenda-se que pacientes com Doença de Fabry realizem acompanhamento renal periódico com o objetivo de evitar a falência renal, uma das principais causas de morte nestes pacientes. Objetivo: Avaliar biomarcadores renais não utilizados na prática clínica de pacientes com Doença de Fabry e comparar com biomarcadores renais utilizados atualmente. Método: Foram quantificados em amostras de sangue e/ou urina os biomarcadores usuais para acompanhamento renal (microalbuminúria, proteinúria e creatinina) bem como os biomarcadores propostos (cistatina C, beta-2-microglobulina, lipocalina associada à gelatinase de neutrófilos (NGAL)) em 40 indivíduos com Doença de Fabry, 39 controles sem doença renal pareados por idade e sexo e 38 controles com doença renal em tratamento de hemodiálise. Resultados: Houve diferença estaticamente significante (p<0,05) tanto nos resultados de soro ou plasma pelo teste de Kruskal-Wallis para cistatina C, NGAL, beta-2-microglobulina, creatinina sérica e taxa de filtração glomerular (TFG) calculada pelos métodos Cockcroft Gault e Modification of Diet in Renal Disease (MDRD) simplificada como em amostras de urina isolada para proteinúria e microalbuminúria pelo teste de Mann-Whitney. Creatinina urinária, pH e densidade urinária não apresentaram diferença estaticamente significante entre os grupos. Todos os parâmetros de avaliação dos biomarcadores renais indicaram a beta-2-microglobulina como melhor biomarcador, seguida de cistatina C, proteinúria e microalbuminúria, respectivamente, enquanto os resultados de NGAL e creatinina urinária não indicam bons preditores de alteração renal. Conclusão: Dos biomarcadores propostos, beta-2-microglobulina em soro mostrou ser o biomarcador renal mais indicado para acompanhamento em pacientes com Doença de Fabry, seguido de cistatina C em plasma. NGAL em plasma demonstrou não ser um bom biomarcador renal. Os resultados de microalbuminúria e proteinúria indicaram alteração renal, porém recomenda-se que análises confirmatórias sejam realizadas. A determinação da TFG por MDRD mostrou ser preferível para a avaliação renal comparada à creatinina sérica. É recomendado que ao menos dois biomarcadores estejam alterados para caracterizar uma alteração renal e, dessa forma, estabelecer a melhor conduta terapêutica para os pacientes com Doença de Fabry.
Introduction: It is recommended that patients with Fabry disease undergo periodic renal monitoring with the aim of avoiding renal failure, one of the main causes of death in these patients. Objective: To evaluate unused renal biomarkers in the clinical practice of patients with Fabry disease and to compare them with renal biomarkers used. Method: The usual biomarkers for renal monitoring (microalbuminuria, proteinuria and creatinine) and the proposed biomarkers (cystatin C, beta-2-microglobulin, neutrophil gelatinase-associated lipocalin (NGAL)) were quantified in blood and/or urine samples in 40 patients with Fabry Disease, 39 controls without renal disease paired by age and sex and 38 controls with renal disease undergoing hemodialysis. Results: There was a significant statistical difference (p <0.05) in both serum and plasma results from the Kruskal-Wallis test for cystatin C, NGAL, beta-2-microglobulin, creatinine and glomerular filtration rates (GFR) by Cockcroft Gault and by Dietary Modification in Renal Disease (MDRD) simplified as in urine samples isolated for protein and microalbuminuria by the Mann-Whitney test. Urinary creatinine, pH and urinary density did not present a significant statistical difference between the groups. All renal biomarkers evaluation parameters indicated beta-2-microglobulin as the best biomarker, followed by cystatin C, proteinuria and microalbuminuria, respectively, while the results of NGAL and urinary creatinine do not indicate good predictors of renal impairment. Conclusion: Of the proposed biomarkers, serum beta-2-microglobulin was the most indicated renal biomarker for follow-up in patients with Fabry disease, followed by cystatin C in plasma. Plasma NGAL has not been shown to be a good renal biomarker. The results of microalbuminuria and proteinuria indicated renal alteration, but it is recommended that they be verified. The determination of GFR by MDRD was shown to be preferable for renal evaluation compared to serum creatinine. It is recommended that at least two biomarkers be altered to characterize a renal alteration, thereby establishing a better therapeutic course for patients with Fabry Disease.
Introduction: It is recommended that patients with Fabry disease undergo periodic renal monitoring with the aim of avoiding renal failure, one of the main causes of death in these patients. Objective: To evaluate unused renal biomarkers in the clinical practice of patients with Fabry disease and to compare them with renal biomarkers used. Method: The usual biomarkers for renal monitoring (microalbuminuria, proteinuria and creatinine) and the proposed biomarkers (cystatin C, beta-2-microglobulin, neutrophil gelatinase-associated lipocalin (NGAL)) were quantified in blood and/or urine samples in 40 patients with Fabry Disease, 39 controls without renal disease paired by age and sex and 38 controls with renal disease undergoing hemodialysis. Results: There was a significant statistical difference (p <0.05) in both serum and plasma results from the Kruskal-Wallis test for cystatin C, NGAL, beta-2-microglobulin, creatinine and glomerular filtration rates (GFR) by Cockcroft Gault and by Dietary Modification in Renal Disease (MDRD) simplified as in urine samples isolated for protein and microalbuminuria by the Mann-Whitney test. Urinary creatinine, pH and urinary density did not present a significant statistical difference between the groups. All renal biomarkers evaluation parameters indicated beta-2-microglobulin as the best biomarker, followed by cystatin C, proteinuria and microalbuminuria, respectively, while the results of NGAL and urinary creatinine do not indicate good predictors of renal impairment. Conclusion: Of the proposed biomarkers, serum beta-2-microglobulin was the most indicated renal biomarker for follow-up in patients with Fabry disease, followed by cystatin C in plasma. Plasma NGAL has not been shown to be a good renal biomarker. The results of microalbuminuria and proteinuria indicated renal alteration, but it is recommended that they be verified. The determination of GFR by MDRD was shown to be preferable for renal evaluation compared to serum creatinine. It is recommended that at least two biomarkers be altered to characterize a renal alteration, thereby establishing a better therapeutic course for patients with Fabry Disease.
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BRAGA, Marion Coting. Análise de biomarcadores renais em pacientes com doença de Fabry. 2018. Dissertação (Mestrado em Pediatria) – Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2018.