Malyszko J, Koc-Zorawska E, Malyszko J S, Mysliwiec M
Department of Nephrology and Transplantology, Medical University, Bialystok, Poland.
Transplant Proc. 2010 Dec;42(10):3957-9. doi: 10.1016/j.transproceed.2010.10.005.
KIM-1 (kidney injury molecule-1) is responsible for the clearance of debris from damaged renal tubules. KIM-1 can be expressed and excreted in urine within 12 hours after the initial ischemic insult and before regeneration of the epithelium, persisting over time thereafter. Urinary KIM-1 has been reported to be a noninvasive, rapid, sensitive, and reproducible biomarker of experimental nephrotoxic and ischemic acute kidney injury. Renal KIM-1 expression is significantly increased in human kidney tissue among patients with a wide range of kidney diseases, including various types of glomerulonephritis, chronic allograft nephropathy, acute rejection, hypertension, and Wegener's granulomatosis. Both renal and urinary KIM-1 correlate with kidney damage and negatively with renal function, but not with proteinuria. The aim of this study was to assess whether urinary KIM-1 correlated with kidney function in kidney allograft recipients.
Serum NGAL, creatinine and estimated glomerular filtration rate (eGFR) were evaluated in 170 kidney allograft recipients on therapy with a calcineurin inhibitor plus mycophenolate mofetil or azathioprine and prednisone as well as in healthy volunteers. KIM-1 was estimated in urine using a commercially available kit.
Kidney transplant recipients showed significantly higher KIM-1 values than the control group. Normotensive kidney allograft recipients displayed significantly lower NGAL results than hypertensive subjects. Urinary KIM-1 was significantly higher among diabetic than nondiabetic subjects, whereas creatinine did not differ significantly between them. Upon univariate analysis urinary KIM-1 strongly correlated with serum creatinine (r = .64) and eGFR (r = -.71), and only weakly with other parameters. Upon multiple regression analysis, the best predictor of urinary KIM-1 was eGFR (beta -0.61), which explained 61% of KIM-1 concentrations.
Even a successful kidney transplantation is associated with kidney injury as reflected by elevated urinary KIM-1 and lower eGFR. Therefore, KIM-1 needs to be investigated as a potential early marker for impaired renal function/kidney injury, especially in patients with other risk factors for damage such as hypertension or diabetes.
肾损伤分子-1(KIM-1)负责清除受损肾小管中的碎片。KIM-1可在初次缺血性损伤后12小时内且上皮细胞再生之前在尿液中表达并排泄,此后会持续存在。据报道,尿KIM-1是实验性肾毒性和缺血性急性肾损伤的一种非侵入性、快速、敏感且可重复的生物标志物。在患有多种肾脏疾病的患者的肾组织中,包括各种类型的肾小球肾炎、慢性移植肾肾病、急性排斥反应、高血压和韦格纳肉芽肿病,肾KIM-1表达显著增加。肾KIM-1和尿KIM-1均与肾损伤相关,与肾功能呈负相关,但与蛋白尿无关。本研究的目的是评估尿KIM-1是否与肾移植受者的肾功能相关。
对170名接受钙调神经磷酸酶抑制剂加霉酚酸酯或硫唑嘌呤及泼尼松治疗的肾移植受者以及健康志愿者进行血清中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肌酐和估计肾小球滤过率(eGFR)评估。使用市售试剂盒对尿液中的KIM-1进行检测。
肾移植受者的KIM-1值显著高于对照组。血压正常的肾移植受者的NGAL结果显著低于高血压患者。糖尿病患者的尿KIM-1显著高于非糖尿病患者,而他们之间的肌酐无显著差异。单因素分析显示,尿KIM-1与血清肌酐(r = 0.64)和eGFR(r = -0.71)密切相关,与其他参数的相关性较弱。多因素回归分析显示,尿KIM-1的最佳预测指标是eGFR(β = -0.61),其可解释KIM-1浓度的61%。
即使是成功的肾移植也与肾损伤相关,表现为尿KIM-1升高和eGFR降低。因此,需要将KIM-1作为肾功能受损/肾损伤的潜在早期标志物进行研究,尤其是在患有高血压或糖尿病等其他损伤风险因素的患者中。