Parikh C R, Mishra J, Thiessen-Philbrook H, Dursun B, Ma Q, Kelly C, Dent C, Devarajan P, Edelstein C L
Section of Nephrology, Yale University, New Haven, Connecticut 06516, USA.
Kidney Int. 2006 Jul;70(1):199-203. doi: 10.1038/sj.ki.5001527. Epub 2006 May 17.
Acute kidney injury (AKI) is a frequent complication of cardiopulmonary bypass (CPB). The lack of early biomarkers for AKI has impaired our ability to intervene in a timely manner. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is recently demonstrated as an early biomarker of AKI after CPB, increasing 25-fold within 2 h and declining 6 h after surgery. In the present study, we tested whether interleukin-18 (IL-18) is a predictive biomarker for AKI in the same group of patients following CPB. Exclusion criteria included pre-existing renal insufficiency and nephrotoxin use. Serial urine samples were analyzed by enzyme-linked immunosorbent assay for IL-18 in 20 patients who developed AKI (defined as a 50% or greater increase in serum creatinine after CPB) and 35 controls (age, race, and gender-matched patients who did not develop AKI after CPB). Using serum creatinine, AKI was detected only 48-72 h after CPB. In contrast, urine IL-18 increased at 4-6 h after CPB, peaked at over 25-fold at 12 h, and remained markedly elevated up to 48 h after CPB. The performance of IL-18 as demonstrated by area under the receiver operating characteristics curve for diagnosis of AKI at 4, 12, and 24 h after CPB was 61, 75, and 73% respectively. Also, on multivariate analysis, both IL-18 and NGAL were independently associated with number of days in AKI among cases. Our results indicate that IL-18 is an early, predictive biomarker of AKI after CPB, and that NGAL and IL-18 are increased in tandem after CPB. The combination of these two biomarkers may allow for the reliable early diagnosis and prognosis of AKI at all times after CPB, much before the rise in serum creatinine.
急性肾损伤（AKI）是体外循环（CPB）常见的并发症。缺乏AKI的早期生物标志物削弱了我们及时干预的能力。尿中性粒细胞明胶酶相关脂质运载蛋白（NGAL）最近被证明是CPB术后AKI的早期生物标志物，在术后2小时内增加25倍，术后6小时下降。在本研究中，我们测试了白细胞介素-18（IL-18）是否是同一组CPB术后患者AKI的预测生物标志物。排除标准包括既往存在肾功能不全和使用肾毒素。通过酶联免疫吸附测定法对20例发生AKI（定义为CPB术后血清肌酐升高50%或更多）的患者和35例对照（年龄、种族和性别匹配且CPB术后未发生AKI的患者）的系列尿样进行IL-18分析。使用血清肌酐，AKI仅在CPB术后48 - 72小时被检测到。相比之下，尿IL-18在CPB术后4 - 6小时升高，在12小时达到超过25倍的峰值，并在CPB术后48小时内一直显著升高。CPB术后4、12和24小时用于诊断AKI的受试者工作特征曲线下面积所显示的IL-18诊断性能分别为61%、75%和73%。此外，多因素分析显示，IL-18和NGAL在病例中均与AKI持续天数独立相关。我们的结果表明，IL-18是CPB术后AKI的早期预测生物标志物，并且CPB术后NGAL和IL-18同步升高。这两种生物标志物的联合使用可能有助于在CPB术后血清肌酐升高之前很久的任何时候对AKI进行可靠的早期诊断和预后评估。
