Department ofNephrology, Hypertension, and Rheumatology, Internal Medicine D, University Hospital Muenster, Albert-Schweitzer-Campus 1, D-48149 Muenster, Germany.
Institute of Sports Medicine, Molecular Genetics of Cardiovascular Disease, University Hospital Muenster, Muenster, Germany.
Nephrol Dial Transplant. 2017 Dec 1;32(12):2090-2097. doi: 10.1093/ndt/gfw334.
Renal and cardiac involvement is responsible for substantial morbidity and mortality in Fabry disease (FD). We analysed the incidence of FD-related renal, cardiac and neurologic end points in patients with FD on long-term enzyme replacement therapy (ERT).
A retrospective analysis of prospectively collected data from two German FD centres was performed. The impact of renal and cardiac function at ERT-naïve baseline on end point development despite ERT was analysed.
Fifty-four patients (28 females) receiving ERT (mean 81 ± 21 months) were investigated. Forty per cent of patients were diagnosed with clinical end points before ERT initiation and 50% of patients on ERT developed new clinical end points. In patients initially diagnosed with an end point before ERT initiation, the risk for an additional end point on ERT was increased {hazard ratio [HR] 3.83 [95% confidence interval (CI) 1.61-9.08]; P = 0.0023}. A decreased glomerular filtration rate (eGFR) ≤75 mL/min/1.73 m2 in ERT-naïve patients at baseline was associated with an increased risk for cardiovascular end points [HR 3.59 (95% CI 1.15-11.18); P = 0.0273] as well as for combined renal, cardiac and neurologic end points on ERT [HR 4.77 (95% CI 1.93-11.81); P = 0.0007]. In patients with normal kidney function, left ventricular hypertrophy at baseline predicted a decreased end point-free survival [HR 6.90 (95% CI 2.04-23.27); P = 0.0018]. The risk to develop an end point was independent of sex.
In addition to age, even moderately impaired renal function determines FD progression on ERT. In patients with FD, renal and cardiac protection is warranted to prevent patients from deleterious manifestations of the disease.
肾脏和心脏的受累是法布瑞病（Fabry disease，FD）患者出现大量发病率和死亡率的主要原因。我们分析了接受长期酶替代疗法（ERT）的 FD 患者的 FD 相关肾脏、心脏和神经系统终点的发生率。
对来自两个德国 FD 中心的前瞻性收集数据进行回顾性分析。分析了 ERT 起始前肾脏和心脏功能对 ERT 后终点发展的影响。
对接受 ERT（平均 81±21 个月）的 54 例患者（28 例女性）进行了研究。40%的患者在 ERT 起始前被诊断为临床终点，50%的患者在 ERT 期间出现新的临床终点。在 ERT 起始前被诊断为终点的患者中，在 ERT 上发生额外终点的风险增加[风险比（HR）3.83（95%置信区间（CI）1.61-9.08）；P=0.0023]。ERT 起始前基线时肾小球滤过率（eGFR）≤75 mL/min/1.73 m2 的患者，发生心血管终点的风险增加[HR 3.59（95%CI 1.15-11.18）；P=0.0273]，以及 ERT 时发生肾脏、心脏和神经系统终点的风险增加[HR 4.77（95%CI 1.93-11.81）；P=0.0007]。在肾功能正常的患者中，基线时左心室肥厚预测终点无事件生存率降低[HR 6.90（95%CI 2.04-23.27）；P=0.0018]。发生终点的风险与性别无关。
除年龄外，即使是中度肾功能不全也会影响 ERT 后的 FD 进展。在 FD 患者中，需要肾脏和心脏保护以防止疾病的不良表现。
