Tahir Hindia, Jackson Leslie L, Warnock David G
Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, AL 35294-0006, USA.
J Am Soc Nephrol. 2007 Sep;18(9):2609-17. doi: 10.1681/ASN.2006121400. Epub 2007 Jul 26.
This report describes an open-label, nonrandomized, prospective evaluation of the effects of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy on patients who have Fabry disease and also received enzyme replacement therapy with agalsidase-beta, given at 1 mg/kg body wt every 2 wk. Previous placebo-controlled phase III and phase IV trials with agalsidase-beta demonstrated clearing of globotriaosylceramide from vascular endothelia but little effect on proteinuria or progressive loss of kidney function in patients with Fabry disease and severe chronic kidney disease marked by overt proteinuria and/or estimated GFR <60 ml/min per 1.73 m2. Angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker therapy is the standard of care for patients with proteinuric kidney diseases, but their use is challenging in patients with Fabry disease and low or low-normal baseline systemic BP. A group of patients with Fabry disease were treated with antiproteinuric therapy, in conjunction with agalsidase-beta; sustained reductions in proteinuria with stabilization of kidney function were achieved in a group of six patients who had severe Fabry nephropathy; the progression rate was -0.23 +/- 1.12 ml/min per 1.73 m2 per yr with 30 mo of follow-up.
本报告描述了一项开放标签、非随机、前瞻性评估,旨在研究血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂疗法对患有法布里病且同时接受β-半乳糖苷酶替代酶疗法(每2周按1mg/kg体重给药)的患者的影响。此前针对β-半乳糖苷酶进行的安慰剂对照III期和IV期试验表明,血管内皮中的球三糖神经酰胺得以清除,但对于以明显蛋白尿和/或估计肾小球滤过率<60ml/min/1.73m²为特征的法布里病和严重慢性肾病患者的蛋白尿或肾功能进行性丧失几乎没有影响。血管紧张素转换酶抑制剂和/或血管紧张素受体阻滞剂疗法是蛋白尿性肾病患者的标准治疗方法,但在基线系统性血压较低或正常下限的法布里病患者中使用具有挑战性。一组法布里病患者接受了抗蛋白尿治疗,并联合使用β-半乳糖苷酶;6名患有严重法布里肾病的患者实现了蛋白尿持续减少且肾功能稳定;随访30个月时,进展速率为-0.23±1.12ml/min/1.73m²/年。