PRESERVE试验使用2×2析因设计比较了静脉内生理盐水溶液与静脉内碳酸氢钠溶液和口服N-乙酰半胱氨酸与安慰剂预防90天主要不良肾脏事件和死亡（MAKE-D）和对比剂-在接受血管造影的慢性肾脏疾病患者中相关的急性肾损伤（CA-AKI）。在这项辅助研究中，我们评估了尿和血浆中血管造影前损伤和修复蛋白对MAKE-D的预测能力，CA-AKI,以及它们对试验设计的影响。
纵向分析。
来自PRESERVE试验的一部分参与者。
伤害（KIM-1，NGAL，和IL-18）和修理（MCP-1，UMOD，血管造影前1至2小时，尿液和血浆中的YKL-40）蛋白。
MAKE-D和CA-AKI。
我们分析了血管造影前生物标志物与MAKE-D和CA-AKI的关联。我们评估了生物标志物水平是否可以丰富的MAKE-D事件率，并通过在线生物标志物预后富集工具提高未来的临床试验效率在prognosticrenumment.com。
我们测量了916名参与者的血浆生物标志物和797名参与者的尿液生物标志物。在调整尿白蛋白-肌酐比值和基线估计的肾小球滤过率之后，4血浆血管造影前水平(KIM-1，NGAL，UMOD,和YKL-40）和3尿（NGAL，IL-18和YKL-40）生物标志物与MAKE-D相关。调整后只有血浆KIM-1水平与CA-AKI显著相关。生物标志物水平为MAKE-D提供了适度的判别能力。使用血管造影前血浆KIM-1或YKL-40水平的第50百分位数筛查患者将使所需的样本量减少30％（约2,000名参与者）。
预后富集的评估并不考虑不断变化的试验成本，筛查患者所需的时间，或后续损失。大多数参与者是男性，限制了我们发现的普遍性。
血管造影前损伤和修复生物标志物水平可适度预测MAKE-D的发展，可用于提高未来CA-AKI试验的效率。
The PRESERVE
trial used a 2 × 2 factorial design to compare intravenous saline solution with intravenous sodium bicarbonate solution and oral N-acetylcysteine with placebo for the prevention of 90-day major adverse kidney events and death (MAKE-D) and contrast-associated acute kidney injury (CA-AKI) among patients with chronic kidney disease undergoing angiography. In this ancillary
study, we evaluated the predictive capacities of preangiography injury and repair proteins in urine and plasma for MAKE-D, CA-AKI, and their impact on
trial design.
Longitudinal analysis.
A subset of participants from the PRESERVE
trial.
Injury (KIM-1, NGAL, and IL-18) and repair (MCP-1, UMOD, and YKL-40) proteins in urine and plasma 1 to 2 hours preangiography.
MAKE-D and CA-AKI.
We analyzed the associations of preangiography biomarkers with MAKE-D and with CA-AKI. We evaluated whether the biomarker levels could enrich the MAKE-D event rate and improve future clinical trial efficiency through an online biomarker prognostic enrichment tool available at prognosticenrichment.com.
We measured plasma biomarkers in 916 participants and urine biomarkers in 797 participants. After adjusting for urinary albumin-creatinine ratio and baseline estimated glomerular filtration rate, preangiography levels of 4 plasma (KIM-1, NGAL, UMOD, and YKL-40) and 3 urine (NGAL, IL-18, and YKL-40) biomarkers were associated with MAKE-D. Only plasma KIM-1 level was significantly associated with CA-AKI after adjustment. Biomarker levels provided modest discriminatory capacity for MAKE-D. Screening patients using the 50th percentile of preangiography plasma KIM-1 or YKL-40 levels would have reduced the required sample size by 30% (∼2,000 participants).
Evaluation of prognostic enrichment does not account for changing
trial costs, time needed to screen patients, or loss to follow-up. Most participants were male, limiting the generalizability of our findings.
Preangiography levels of injury and repair biomarkers modestly predict the development of MAKE-D and can be used to improve the efficiency of future CA-AKI trials.
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