Vaidya Vishal S, Ford Glen M, Waikar Sushrut S, Wang Yizhuo, Clement Matthew B, Ramirez Victoria, Glaab Warren E, Troth Sean P, Sistare Frank D, Prozialeck Walter C, Edwards Joshua R, Bobadilla Norma A, Mefferd Stephen C, Bonventre Joseph V
Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Kidney Int. 2009 Jul;76(1):108-14. doi: 10.1038/ki.2009.96. Epub 2009 Apr 22.
Kidney injury molecule-1 (Kim-1) has been qualified by the Food and Drug Administration and European Medicines Agency as a highly sensitive and specific urinary biomarker to monitor drug-induced kidney injury in preclinical studies and on a case-by-case basis in clinical trials. Here we report the development and evaluation of a rapid direct immunochromatographic lateral flow 15-min assay for detection of urinary Kim-1 (rat) or KIM-1 (human). The urinary Kim-1 band intensity using the rat Kim-1 dipstick significantly correlated with levels of Kim-1 as measured by a microbead-based assay, histopathological damage, and immunohistochemical assessment of renal Kim-1 in a dose- and time-dependent manner. Kim-1 was detected following kidney injury induced in rats by cadmium, gentamicin, or bilateral renal ischemia/reperfusion. In humans, the urinary KIM-1 band intensity was significantly greater in urine from patients with acute kidney injury than in urine from healthy volunteers. The KIM-1 dipstick also enabled temporal evaluation of kidney injury and recovery in two patients who developed postoperative acute kidney injury following cytoreductive surgery for malignant mesothelioma with intraoperative local cisplatin administration. We hope that future, more extensive studies will confirm the utility of these results, which show that the Kim-1/KIM-1 dipsticks can provide a sensitive and accurate detection of Kim-1/KIM-1, thereby providing a rapid diagnostic assay for kidney damage and facilitating the rapid and early detection of kidney injury in preclinical and clinical studies.
肾损伤分子-1(Kim-1)已被美国食品药品监督管理局和欧洲药品管理局认定为一种高度敏感且特异的尿液生物标志物,可在临床前研究以及临床试验中逐案监测药物性肾损伤。在此,我们报告了一种用于检测尿液中Kim-1(大鼠)或KIM-1(人类)的快速直接免疫层析侧向流动15分钟检测方法的开发与评估。使用大鼠Kim-1试纸条检测到的尿液Kim-1条带强度与基于微珠检测法测得的Kim-1水平、组织病理学损伤以及肾脏Kim-1的免疫组织化学评估呈剂量和时间依赖性显著相关。在大鼠经镉、庆大霉素诱导肾损伤或双侧肾缺血/再灌注后检测到了Kim-1。在人类中,急性肾损伤患者尿液中的尿KIM-1条带强度显著高于健康志愿者尿液中的强度。KIM-1试纸条还能够对两名在术中局部给予顺铂的恶性间皮瘤细胞减灭术后发生术后急性肾损伤的患者的肾损伤和恢复情况进行实时评估。我们希望未来更广泛的研究能够证实这些结果的实用性,即Kim-1/KIM-1试纸条能够灵敏且准确地检测Kim-1/KIM-1,从而为肾损伤提供一种快速诊断检测方法,并有助于在临床前和临床研究中快速早期检测肾损伤。