Department of Nephrology, The Royal Melbourne Hospital, Parkville, Melbourne, Australia.
Nephrol Dial Transplant. 2011 Oct;26(10):3195-202. doi: 10.1093/ndt/gfr084. Epub 2011 Mar 7.
Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder resulting from the deficiency of trihexosylceramide α-galactosidase (α-Gal A). The diagnosis is often missed or delayed, and specific diagnostic tests (serum α-Gal A activity, genotyping or biopsy) are expensive and not widely available. We evaluated the diagnostic potential of urine microscopy in AFD.
We studied 35 male and female AFD patients across a wide phenotypic spectrum and 21 controls with other renal diseases. Fresh urine sediment was examined under phase-contrast microscopy using polarized light for Maltese cross (MC) particles, anti-CD77 antibody to detect globotriaosylceramide (GL3, the substrate of α-Gal A), and anti-podocalyxin antibody to assess podocyte excretion.
Characteristic MC 2 particles and anti-CD77 binding within vacuolated urinary epithelial cells were both detected in AFD with high sensitivity and specificity (MC 2 detection sensitivity 100%, 95% confidence interval (CI) 85.4-100%, specificity 100%, CI 80.8-100%; anti-CD77-binding sensitivity 97.1%, CI 83.3-99.9, specificity 100%, CI 80.8-100%). Albuminuria (urinary albumin-to-creatinine ratio, ACR) correlated with quantitative particle excretion--in low, intermediate and high MC excretors, and median ACR was 1.6, 6.9 and 20.0 mg/μmol, respectively (analysis of variance P = 0.017). Podocyte staining was positive in ~50% of all AFD patients and was similar in those with and without clinical Fabry nephropathy (FN), whether or not treated with enzyme replacement.
Targeted urinary microscopy is a non-invasive, inexpensive, accessible and rapid diagnostic technique, especially applicable where serum α-Gal A activity and genotyping are not affordable or available. As the number of urinary MC 2 particles increases with rising albuminuria, the technique may also be useful in assessing FN burden.
安德森-法布里病（AFD）是一种 X 连锁溶酶体贮积症，由三己糖神经酰胺 α-半乳糖苷酶（α-Gal A）缺乏引起。该疾病的诊断常常被忽视或延迟，而特定的诊断测试（血清α-Gal A 活性、基因分型或活组织检查）昂贵且并不广泛可用。我们评估了尿液显微镜检查在 AFD 中的诊断潜力。
我们研究了跨越广泛表型谱的 35 名男性和女性 AFD 患者以及 21 名患有其他肾脏疾病的对照者。使用相差显微镜和偏光显微镜检查新鲜尿液沉淀物中的马耳他十字（MC）颗粒，使用抗-CD77 抗体检测神经节苷脂（GL3，α-Gal A 的底物），并使用抗足细胞蛋白抗体评估足细胞排泄。
在 AFD 中，MC2 颗粒和空泡化尿上皮细胞内的抗-CD77 结合均具有高灵敏度和特异性（MC2 检测灵敏度 100%，95%置信区间[CI]85.4-100%，特异性 100%，CI 80.8-100%；抗-CD77 结合敏感性 97.1%，CI 83.3-99.9%，特异性 100%，CI 80.8-100%）。白蛋白尿（尿白蛋白与肌酐比值，ACR）与定量颗粒排泄相关-在低、中、高 MC 排泄者中，ACR 中位数分别为 1.6、6.9 和 20.0mg/μmol（方差分析 P=0.017）。约 50%的所有 AFD 患者的足细胞染色呈阳性，且在有无临床 Fabry 肾病（FN）、是否接受酶替代治疗的患者中均相似。
靶向尿液显微镜检查是一种非侵入性、廉价、可及和快速的诊断技术，尤其适用于无法获得或负担得起血清α-Gal A 活性和基因分型的情况。随着白蛋白尿中 MC2 颗粒数量的增加，该技术也可用于评估 FN 负担。
