Moledina Dennis G, Hall Isaac E, Thiessen-Philbrook Heather, Reese Peter P, Weng Francis L, Schröppel Bernd, Doshi Mona D, Wilson F Perry, Coca Steven G, Parikh Chirag R
Program of Applied Translational Research, Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT.
Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT.
Am J Kidney Dis. 2017 Dec;70(6):807-816. doi: 10.1053/j.ajkd.2017.06.031. Epub 2017 Aug 24.
The diagnosis of acute kidney injury (AKI), which is currently defined as an increase in serum creatinine (Scr) concentration, provides little information on the condition's actual cause. To improve phenotyping of AKI, many urinary biomarkers of tubular injury are being investigated. Because AKI cases are not frequently biopsied, the diagnostic accuracy of concentrations of Scr and urinary biomarkers for histologic acute tubular injury is unknown.
Cross-sectional analysis from multicenter prospective cohort.
SETTINGS & PARTICIPANTS: Hospitalized deceased kidney donors on whom kidney biopsies were performed at the time of organ procurement for histologic evaluation.
(1) AKI diagnosed by change in Scr concentration during donor hospitalization and (2) concentrations of urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], liver-type fatty acid-binding protein [L-FABP], interleukin 18 [IL-18], and kidney injury molecule 1 [KIM-1]) measured at organ procurement.
Histologic acute tubular injury.
Of 581 donors, 98 (17%) had mild acute tubular injury and 57 (10%) had severe acute tubular injury. Overall, Scr-based AKI had poor diagnostic performance for identifying histologic acute tubular injury and 49% of donors with severe acute tubular injury did not have AKI. The area under the receiver operating characteristic curve (AUROC) of change in Scr concentration for diagnosing severe acute tubular injury was 0.58 (95% CI, 0.49-0.67) and for any acute tubular injury was 0.52 (95% CI, 0.45-0.58). Compared with Scr concentration, NGAL concentration demonstrated higher AUROC for diagnosing both severe acute tubular injury (0.67; 95% CI, 0.60-0.74; P=0.03) and any acute tubular injury (0.60; 95% CI, 0.55-0.66; P=0.005). In donors who did not have Scr-based AKI, NGAL concentrations were higher with increasing severities of acute tubular injury (subclinical AKI). However, compared with Scr concentration, AUROCs for acute tubular injury diagnosis were not significantly higher for urinary L-FABP, IL-18, or KIM-1.
The spectrum of AKI cause in deceased donors may be different from that of a general hospitalized population.
Concentrations of Scr and kidney injury biomarkers (L-FABP, IL-18, and KIM-1) lack accuracy for diagnosing acute tubular injury in hospitalized deceased donors. Although urinary NGAL concentration had slightly higher discrimination for acute tubular injury than did Scr concentration, its overall AUROC was still modest.
急性肾损伤（AKI）目前定义为血清肌酐（Scr）浓度升高，关于该病症的实际病因，此定义提供的信息很少。为改善AKI的表型分析，目前正在研究许多肾小管损伤的尿液生物标志物。由于AKI病例不常进行活检，Scr浓度和尿液生物标志物浓度对组织学急性肾小管损伤的诊断准确性尚不清楚。
多中心前瞻性队列的横断面分析。
住院死亡的肾脏捐献者，在器官获取时进行肾脏活检以进行组织学评估。
（1）根据捐献者住院期间Scr浓度变化诊断的AKI；（2）在器官获取时测量的尿液生物标志物（中性粒细胞明胶酶相关脂质运载蛋白[NGAL]、肝型脂肪酸结合蛋白[L-FABP]、白细胞介素18[IL-18]和肾损伤分子1[KIM-1]）浓度。
组织学急性肾小管损伤。
在581名捐献者中，98名（17%）有轻度急性肾小管损伤，57名（10%）有重度急性肾小管损伤。总体而言，基于Scr的AKI在识别组织学急性肾小管损伤方面诊断性能较差，49%的重度急性肾小管损伤捐献者没有AKI。Scr浓度变化用于诊断重度急性肾小管损伤的受试者工作特征曲线下面积（AUROC）为0.58（95%CI，0.49-0.67），用于诊断任何急性肾小管损伤的AUROC为0.52（95%CI，0.45-0.58）。与Scr浓度相比，NGAL浓度在诊断重度急性肾小管损伤（0.67；95%CI，0.60-0.74；P=0.03）和任何急性肾小管损伤（0.60；95%CI，0.55-0.66；P=0.005）方面均显示出更高的AUROC。在没有基于Scr的AKI的捐献者中，随着急性肾小管损伤（亚临床AKI）严重程度的增加，NGAL浓度升高。然而，与Scr浓度相比，尿液L-FABP、IL-18或KIM-1用于急性肾小管损伤诊断的AUROC并没有显著更高。
死亡捐献者中AKI病因的范围可能与一般住院人群不同。
Scr浓度和肾损伤生物标志物（L-FABP、IL-18和KIM-1）在诊断住院死亡捐献者的急性肾小管损伤方面缺乏准确性。尽管尿液NGAL浓度对急性肾小管损伤的鉴别能力略高于Scr浓度，但其总体AUROC仍然一般。
