Skrunes Rannveig, Svarstad Einar, Kampevold Larsen Kristin, Leh Sabine, Tøndel Camilla
Department of Medicine, Haukeland University Hospital, Bergen, Norway.
Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Nephrol Dial Transplant. 2017 May 1;32(5):807-813. doi: 10.1093/ndt/gfw094.
Agalsidase-α 0.2 mg/kg every other week (eow) and agalsidase-β 1.0 mg/kg/eow are licensed in Europe as equipotent treatment of the α-galactosidase deficiency in Fabry disease. This case series describes the effects of agalsidase dose adjustments in serial kidney biopsies in switch patients.
All treatment-naïve patients with classical Fabry disease in our centre started on agalsidase-β 1.0 mg/kg/eow and subsequently switched to agalsidase-α 0.2 mg/kg/eow were included ( n = 3). The median age at enzyme replacement therapy start was 11 (range 7-18) years. Kidney biopsies were performed at baseline, after 5 years of agalsidase-β 1.0 mg/kg/eow and after 3 subsequent years of agalsidase-α 0.2 mg/kg/eow. One patient was re-biopsied 2 years after reswitch to agalsidase-β 1.0 mg/kg/eow. The scoring system of the International Scoring Group of Fabry Nephropathy was used.
The patients completely cleared globotriaosylceramide (GL3) from mesangial and endothelial cells and partly cleared podocytes on agalsidase-β 1.0 mg/kg/eow. Reaccumulation of GL3 in podocytes, but not in the mesangium or endothelium, occurred after 3 years of agalsidase-α 0.2 mg/kg/eow. Subsequent reduction of podocyte GL3 was observed in the single patient rebiopsied 2 years after reswitch to agalsidase-β 1.0 mg/kg/eow.
Partial clearance, reaccumulation and renewed partial clearance of podocyte GL3 deposits in serial kidney biopsies over 8-10 years were seen in parallel with agalsidase dose adjustments. Repeated kidney biopsies may impact therapeutic choices in Fabry disease.
在欧洲，每隔一周一次（eow）给予0.2mg/kg的α-半乳糖苷酶α和1.0mg/kg/eow的α-半乳糖苷酶β被许可用于法布里病中α-半乳糖苷酶缺乏的等效治疗。本病例系列描述了转换治疗的患者在连续肾脏活检中α-半乳糖苷酶剂量调整的效果。
纳入了所有在我们中心开始接受1.0mg/kg/eow的α-半乳糖苷酶β治疗，随后转换为0.2mg/kg/eow的α-半乳糖苷酶α治疗的初治经典法布里病患者（n = 3）。开始酶替代治疗时的中位年龄为11岁（范围7 - 18岁）。在基线、接受1.0mg/kg/eow的α-半乳糖苷酶β治疗5年后以及随后接受0.2mg/kg/eow的α-半乳糖苷酶α治疗3年后进行肾脏活检。一名患者在重新转换为1.0mg/kg/eow的α-半乳糖苷酶β治疗2年后再次进行活检。使用了法布里肾病国际评分组的评分系统。
患者在接受1.0mg/kg/eow的α-半乳糖苷酶β治疗时，系膜细胞和内皮细胞中的球三糖神经酰胺（GL3）完全清除，足细胞中的GL3部分清除。在接受0.2mg/kg/eow的α-半乳糖苷酶α治疗3年后，足细胞中出现GL3再蓄积，但系膜或内皮中未出现。在重新转换为1.0mg/kg/eow的α-半乳糖苷酶β治疗2年后再次活检的单一患者中观察到足细胞GL3随后减少。
在8 - 10年的连续肾脏活检中，足细胞GL3沉积物出现部分清除、再蓄积和再次部分清除，这与α-半乳糖苷酶剂量调整同时发生。重复肾脏活检可能会影响法布里病的治疗选择。
