University of Alabama at Birmingham, Birmingham, AL, USA.
Nephrol Dial Transplant. 2012 Mar;27(3):1042-9. doi: 10.1093/ndt/gfr420. Epub 2011 Jul 29.
The purpose of this study was to identify determinants of renal disease progression in adults with Fabry disease during treatment with agalsidase beta.
Renal function was evaluated in 151 men and 62 women from the Fabry Registry who received agalsidase beta at an average dose of 1 mg/kg/2 weeks for at least 2 years. Patients were categorized into quartiles based on slopes of estimated glomerular filtration rate (eGFR) during treatment. Multivariate logistic regression analyses were used to identify factors associated with renal disease progression.
Men within the first quartile had a mean eGFR slope of -0.1 mL/min/1.73m(2)/year, whereas men with the most rapid renal disease progression (Quartile 4) had a mean eGFR slope of -6.7 mL/min/1.73m(2)/year. The risk factor most strongly associated with renal disease progression was averaged urinary protein:creatinine ratio (UP/Cr) ≥1 g/g (odds ratio 112, 95% confidence interval (95% CI) 4-3109, P = 0.0054). Longer time from symptom onset to treatment was also associated with renal disease progression (odds ratio 19, 95% CI 2-184, P = 0.0098). Women in Quartile 4 had the highest averaged UP/Cr (mean 1.8 g/g) and the most rapid renal disease progression: (mean slope -4.4 mL/min/1.73m(2)/year).
Adults with Fabry disease are at risk for progressive loss of eGFR despite enzyme replacement therapy, particularly if proteinuria is ≥1 g/g. Men with little urinary protein excretion and those who began receiving agalsidase beta sooner after the onset of symptoms had stable renal function. These findings suggest that early intervention may lead to optimal renal outcomes.
本研究旨在确定接受阿加糖酶β治疗的法布瑞病成人患者肾功能进展的决定因素。
对接受阿加糖酶β治疗至少 2 年、平均剂量为 1 mg/kg/2 周的 151 名男性和 62 名女性患者进行了肾功能评估。根据治疗期间估算肾小球滤过率（eGFR）斜率，将患者分为 4 个四分位组。采用多变量逻辑回归分析确定与肾脏疾病进展相关的因素。
第 1 四分位数组男性的平均 eGFR 斜率为-0.1 mL/min/1.73m²/年，而肾脏疾病进展最快（第 4 四分位数）的男性平均 eGFR 斜率为-6.7 mL/min/1.73m²/年。与肾脏疾病进展最密切相关的危险因素是平均尿蛋白与肌酐比值（UP/Cr）≥1 g/g（比值比 112，95%置信区间[95%CI] 4-3109，P=0.0054）。从症状发作到治疗的时间延长也与肾脏疾病进展相关（比值比 19，95%CI 2-184，P=0.0098）。第 4 四分位数的女性平均 UP/Cr（1.8 g/g）最高，肾脏疾病进展最快（平均斜率-4.4 mL/min/1.73m²/年）。
尽管接受了酶替代治疗，但法布瑞病成人仍有发生 eGFR 进行性下降的风险，尤其是蛋白尿≥1 g/g 时。尿蛋白排泄少的男性和症状发作后尽快开始接受阿加糖酶β治疗的男性肾功能稳定。这些发现表明早期干预可能会导致最佳的肾脏结局。
