Zhang P L, Rothblum L I, Han W K, Blasick T M, Potdar S, Bonventre J V
Division of Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania, USA.
Kidney Int. 2008 Mar;73(5):608-14. doi: 10.1038/sj.ki.5002697. Epub 2007 Dec 26.
Kidney injury molecule-1 (KIM-1) is a specific histological biomarker for diagnosing early tubular injury on renal biopsies. In this study, KIM-1 expression was quantitated in renal transplant biopsies by immunohistochemistry and correlated with renal function. None of the 25 protocol biopsies showed detectable tubular injury on histologic examination, yet 28% had focal positive KIM-1 expression. Proximal tubule KIM-1 expression was present in all biopsies from patients with histological changes showing acute tubular damage and deterioration of kidney function. In this group, higher KIM-1 staining predicted a better outcome with improved blood urea nitrogen (BUN), serum creatinine, and estimated glomerular filtration rate (eGFR) over an ensuing 18 months. KIM-1 was expressed focally in affected tubules in 92% of kidney biopsies from patients with acute cellular rejection. By contrast, there was little positive staining for Ki-67, a cell proliferation marker, in any of the groups. KIM-1 expression significantly correlated with serum creatinine and BUN, and inversely with the eGFR on the biopsy day. Our study shows that KIM-1 staining sensitively and specifically identified proximal tubular injury and correlated with the degree of renal dysfunction. KIM-1 expression is more sensitive than histology for detecting early tubular injury, and its level of expression in transplant biopsies may indicate the potential for recovery of kidney function.
肾损伤分子-1(KIM-1)是诊断肾活检早期肾小管损伤的一种特异性组织学生物标志物。在本研究中,通过免疫组织化学对肾移植活检组织中的KIM-1表达进行定量,并将其与肾功能相关联。25例方案活检组织在组织学检查中均未显示可检测到的肾小管损伤,但28%有局灶性KIM-1阳性表达。在组织学改变显示急性肾小管损伤和肾功能恶化的患者的所有活检组织中均存在近端肾小管KIM-1表达。在该组中,较高的KIM-1染色预示着在随后18个月中血尿素氮(BUN)、血清肌酐和估计肾小球滤过率(eGFR)改善的更好结局。在急性细胞排斥患者的92%的肾活检组织中,KIM-1在受影响的肾小管中局灶性表达。相比之下,在任何组中细胞增殖标志物Ki-67几乎没有阳性染色。在活检当天,KIM-1表达与血清肌酐和BUN显著相关,与eGFR呈负相关。我们的研究表明,KIM-1染色灵敏且特异地识别近端肾小管损伤,并与肾功能障碍程度相关。KIM-1表达在检测早期肾小管损伤方面比组织学更敏感,其在移植活检组织中的表达水平可能表明肾功能恢复的潜力。