Christchurch Kidney Research Group, Department of Medicine, University of Otago, Christchurch, New Zealand.
Kidney Int. 2010 Jun;77(11):1020-30. doi: 10.1038/ki.2010.25. Epub 2010 Feb 17.
We performed a double-blind placebo-controlled trial to study whether early treatment with erythropoietin could prevent the development of acute kidney injury in patients in two general intensive care units. As a guide for choosing the patients for treatment we measured urinary levels of two biomarkers, the proximal tubular brush border enzymes gamma-glutamyl transpeptidase and alkaline phosphatase. Randomization to either placebo or two doses of erythropoietin was triggered by an increase in the biomarker concentration product to levels above 46.3, with a primary outcome of relative average plasma creatinine increase from baseline over 4 to 7 days. Of 529 patients, 162 were randomized within an average of 3.5 h of a positive sample. There was no difference in the incidence of erythropoietin-specific adverse events or in the primary outcome between the placebo and treatment groups. The triggering biomarker concentration product selected patients with more severe illness and at greater risk of acute kidney injury, dialysis, or death; however, the marker elevations were transient. Early intervention with high-dose erythropoietin was safe but did not alter the outcome. Although these two urine biomarkers facilitated our early intervention, their transient increase compromised effective triaging. Further, our study showed that a composite of these two biomarkers was insufficient for risk stratification in a patient population with a heterogeneous onset of injury.
我们进行了一项双盲安慰剂对照试验，以研究早期使用促红细胞生成素是否可以预防两个普通重症监护病房患者的急性肾损伤的发展。作为治疗患者的指导，我们测量了两种生物标志物（近端肾小管刷状缘酶γ-谷氨酰转肽酶和碱性磷酸酶）的尿水平。通过生物标志物浓度乘积增加到 46.3 以上来触发随机分配至安慰剂或两种剂量促红细胞生成素，主要结局是相对平均血浆肌酐从基线增加 4 到 7 天。在 529 名患者中，有 162 名在阳性样本后平均 3.5 小时内被随机分配。在促红细胞生成素特异性不良事件发生率或主要结局方面，安慰剂组和治疗组之间没有差异。触发生物标志物浓度乘积选择了病情更严重、急性肾损伤、透析或死亡风险更高的患者；然而，标志物升高是短暂的。早期使用高剂量促红细胞生成素是安全的，但并未改变结果。尽管这两种尿生物标志物有助于我们进行早期干预，但它们的短暂升高会影响有效的分类。此外，我们的研究表明，在损伤起始时间不同的患者人群中，这两种生物标志物的组合不足以进行风险分层。
