Sections of Nephrology & Biomedical Proteomics, Health Sciences Centre, GE421C, 820 Sherbrooke Street, Winnipeg, Manitoba, MB R3A 1R9, Canada.
Clin J Am Soc Nephrol. 2011 Oct;6(10):2340-6. doi: 10.2215/CJN.01000211. Epub 2011 Sep 1.
Acute kidney injury (AKI) complicating cardiopulmonary bypass (CPB) results in increased morbidity and mortality. Urinary hepcidin-25 has been shown to be elevated in patients who do not develop AKI after CPB using semiquantitative mass spectrometry (SELDI TOF-MS). The goals of this study were to quantitatively validate these findings with ELISA and evaluate the diagnostic performance of hepcidin-25 for AKI.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A nested, case-control analysis of urinary hepcidin-25 in AKI (n = 22) and non-AKI (n = 22) patients was conducted to validate the SELDI TOF-MS data at the following times: preoperatively; the start of CPB; 1 hour on CPB; on arrival to the intensive care unit; and postoperative days (POD) 1 and 3 to 5. The diagnostic performance of hepcidin-25 was then evaluated in the entire prospective observational cohort (n = 338) at POD 1. AKI was defined as Cr >50% from baseline, within 72 hours postoperatively.
Urinary hepcidin-25/Cr ratio was significantly elevated in all patients at POD 1 compared with baseline (P < 0.0005) and was also significantly elevated in non-AKI versus AKI patients at POD 1 (P < 0.0005). Increased log(10) hepcidin-25/Cr ratio was strongly associated with avoidance of AKI on univariate analysis. On multivariate analysis, the log(10) hepcidin-25/Cr ratio (P < 0.0001) was associated with avoidance of AKI with an area under the curve of 0.80, sensitivity 0.68, specificity 0.68, and negative predictive value 0.96.
Elevated urinary hepcidin-25 on POD 1 is a strong predictor of avoidance of AKI beyond postoperative day 1.
体外循环（CPB）并发急性肾损伤（AKI）会增加发病率和死亡率。使用半定量质谱（SELDI-TOF-MS）发现，CPB 后未发生 AKI 的患者尿液中的肝素素-25 升高。本研究的目的是使用 ELISA 定量验证这些发现，并评估肝素素-25 对 AKI 的诊断性能。
设计、设置、参与者和测量：对 AKI（n=22）和非 AKI（n=22）患者的尿液肝素素-25 进行嵌套病例对照分析，以验证 SELDI-TOF-MS 数据在以下时间点的结果：术前；CPB 开始时；CPB 1 小时后；到达重症监护病房时；术后第 1 天和第 3 天至第 5 天。然后在整个前瞻性观察队列（n=338）中评估肝素素-25 在术后第 1 天的诊断性能。AKI 的定义为术后 72 小时内 Cr 比基线升高 50%以上。
与基线相比，所有患者在术后第 1 天的尿肝素素-25/Cr 比值均显著升高（P<0.0005），且非 AKI 患者与 AKI 患者相比也显著升高（P<0.0005）。在单变量分析中，肝素素-25/Cr 比值的对数增加与避免 AKI 强烈相关。在多变量分析中，肝素素-25/Cr 比值的对数（P<0.0001）与避免 AKI 相关，曲线下面积为 0.80，灵敏度 0.68，特异性 0.68，阴性预测值 0.96。
术后第 1 天尿肝素素-25 升高是术后第 1 天避免 AKI 的有力预测指标。
