Curso de Especialização em Análises Clínicas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
Clin Chim Acta. 2018 Mar;478:62-67. doi: 10.1016/j.cca.2017.12.033. Epub 2017 Dec 21.
Fabry disease (FD) is a disorder that results from mutations of hydrolase α-galactosidase A. The enzymatic defect leads to accumulation of globotriaosylceramide (Gb3) in the kidney. Substrate deposition is related to tissue damage in FD, but the relation of urinary Gb3 levels in patients and the renal function markers remain not completely understood. Once nephropathy is one of the main features of FD and is marked by an insidious development, we investigated a possible correlation of Gb3 with biochemical markers of nephropathy including albuminuria, estimated glomerular filtration rate (eGFR), serum creatinine and urea, and proteinuria in male and female patients under or not enzyme replacement therapy (ERT).Gb3, proteinuria and albuminuria were increased in male and female FD patients. We found no correlation between urinary Gb3 levels and all renal function parameters evaluated in Fabry patients (in both sexes and using or not ERT). On the other hand, albuminuria showed negative correlation with eGFR only in male under or not ERT, demonstrating that albuminuria seems to be an early marker of renal function alteration. In conclusion, the results suggest that urinary Gb3 level does not reflect the renal function and that albuminuria is an important biomarker in male FD patients.
法布雷病(FD)是一种由于α-半乳糖苷酶 A 水解酶基因突变引起的疾病。酶缺陷导致糖鞘脂类(Gb3)在肾脏中积累。底物沉积与 FD 中的组织损伤有关,但患者尿液 Gb3 水平与肾功能标志物之间的关系尚未完全清楚。由于肾病是 FD 的主要特征之一,且其发展隐匿,因此我们研究了 Gb3 与包括蛋白尿、估算肾小球滤过率(eGFR)、血清肌酐和尿素在内的肾病生化标志物以及蛋白尿之间的可能相关性,这些标志物在接受或未接受酶替代疗法(ERT)的男性和女性 FD 患者中均有体现。男性和女性 FD 患者的 Gb3、蛋白尿和白蛋白尿均增加。我们发现 Fabry 患者(无论男女,无论是否接受 ERT)的尿液 Gb3 水平与所有肾功能参数之间均无相关性。另一方面,白蛋白尿仅在接受或未接受 ERT 的男性中与 eGFR 呈负相关,表明白蛋白尿似乎是肾功能改变的早期标志物。总之,这些结果表明,尿液 Gb3 水平不能反映肾功能,而白蛋白尿是男性 FD 患者的一个重要生物标志物。