Warnock David G, Thomas Christie P, Vujkovac Bojan, Campbell Ruth C, Charrow Joel, Laney Dawn A, Jackson Leslie L, Wilcox William R, Wanner Christoph
Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
J Med Genet. 2015 Dec;52(12):860-6. doi: 10.1136/jmedgenet-2015-103471. Epub 2015 Oct 21.
Nephropathy is an important feature of classical Fabry disease, which results in alpha-galactosidase A deficiency and cellular globotriaosylceramide accumulation. We report the safety and efficacy of antiproteinuric therapy with ACE inhibitors or angiotensin II receptor blockers (ARBs) in a study of classical Fabry patients receiving recombinant agalsidase-beta therapy.
The goal was maintenance of urine protein to creatinine ratio (UPCR) <0.5 g/g or a 50% reduction in baseline UPCR for 24 patients at eight study sites. The change in estimated glomerular filtration rate (eGFR) was assessed over 21 months of treatment.
18 out of 24 patients achieved the UPCR goal with eGFR slopes that were significantly better than six patients who did not achieve the UPCR goal (-3.6 (-4.8 to -1.1) versus -7.0 (-9.0 to -5.6) mL/min/1.73 m(2)/year, respectively, p=0.018). Despite achieving the UPCR goal, 67% (12/18 patients) still progressed with an eGFR slope <-2 mL/min/1.73 m(2)/year. Regression analysis showed that increased age at initiation of agalsidase-beta therapy was significantly associated with worsened kidney outcome. Hypotension and hyperkalaemia occurred in seven and eight patients, respectively, which required modification of antiproteinuric therapy but was not associated with serious adverse events.
This study documents the effectiveness of agalsidase-beta (1 mg/kg/2 weeks) and antiproteinuric therapy with ACE inhibitors and/or ARB in patients with severe Fabry nephropathy. Patients had preservation of kidney function if agalsidase-beta treatment was initiated at a younger age, and UPCR maintained at or below 0.5 g/g with antiproteinuric therapy.
NCT00446862.
肾病是典型法布里病的一个重要特征，该病导致α-半乳糖苷酶A缺乏和细胞内球三糖神经酰胺蓄积。我们在一项针对接受重组β-半乳糖苷酶治疗的典型法布里病患者的研究中，报告了使用血管紧张素转换酶抑制剂（ACE抑制剂）或血管紧张素II受体阻滞剂（ARB）进行抗蛋白尿治疗的安全性和有效性。
目标是在8个研究地点的24例患者中，将尿蛋白与肌酐比值（UPCR）维持在<0.5 g/g，或使基线UPCR降低50%。在21个月的治疗期间评估估计肾小球滤过率（eGFR）的变化。
24例患者中有18例达到了UPCR目标，其eGFR斜率显著优于未达到UPCR目标的6例患者（分别为-3.6（-4.8至-1.1）与-7.0（-9.0至-5.6）mL/min/1.73 m²/年，p=0.018）。尽管达到了UPCR目标，但67%（12/18例患者）的eGFR斜率仍<-2 mL/min/1.73 m²/年，病情仍在进展。回归分析显示，开始β-半乳糖苷酶治疗时年龄增加与肾脏预后恶化显著相关。分别有7例和8例患者发生低血压和高钾血症，这需要调整抗蛋白尿治疗，但未发生严重不良事件。
本研究证明了β-半乳糖苷酶（1 mg/kg/每2周）以及使用ACE抑制剂和/或ARB进行抗蛋白尿治疗对重度法布里肾病患者的有效性。如果在较年轻时开始β-半乳糖苷酶治疗，且通过抗蛋白尿治疗将UPCR维持在或低于0.5 g/g，则患者的肾功能可得到保留。
NCT00446862。
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