Zhang Yan, Oetting William S, Harvey Stephen B, Stone Matthew D, Monkkonen Teresa, Matas Arthur J, Cosio Fernando G, Nelsestuen Gary L
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
Transplantation. 2009 Jun 27;87(12):1807-13. doi: 10.1097/TP.0b013e3181a66595.
The use of biopsies to determine kidney health after kidney transplantation is an invasive procedure with some risk to the patient. Consequently, a noninvasive test for transplanted kidney health would provide a significant advantage over current clinical practice.
Urines from kidney donors before nephrectomy, pretransplant patients with native kidney disease, and posttransplant kidney recipients were examined for protein biomarkers to diagnose or prognose kidney disease. Proteins were extracted by C4 reverse phase affinity and analyzed by matrix assisted laser desorption/ionization time-of-flight mass spectrometry.
Urine from individuals with healthy kidneys showed few components other than two ubiquitous saposin B glycoisoforms. Patients with kidney disease lacked saposin B and showed new components in two patterns: the most common contained beta-2 microglobulin (B2M, m/z=11,732) plus one or more peaks at m/z=10,350, 9480, 4337, and 4180. Pattern 2 lacked beta-2 microglobulin but contained several degradation products of alpha-1 antitrypsin. Other pathologic components included urinary protein 1 (m/z=15,835), transthyretin (m/z=13,880), and a component at m/z=13,350.
Patients with acute rejection showed profiles that ranged from those of kidney donors to those of advanced kidney disease. The range of patterns may be useful for analysis of transplant patients without complications and persons with developing kidney disease before or after transplant.
使用活检来确定肾移植后肾脏健康状况是一种侵入性操作,对患者有一定风险。因此,一种用于检测移植肾健康状况的非侵入性检测方法将比当前临床实践具有显著优势。
对肾切除术前的肾脏供体、移植前患有原发性肾脏疾病的患者以及移植后肾受体的尿液进行检测,以寻找用于诊断或预测肾脏疾病的蛋白质生物标志物。通过C4反相亲和法提取蛋白质,并采用基质辅助激光解吸/电离飞行时间质谱法进行分析。
健康肾脏个体的尿液中,除了两种普遍存在的鞘脂激活蛋白B糖异构体之外,几乎没有其他成分。患有肾脏疾病的患者缺乏鞘脂激活蛋白B,并呈现出两种模式的新成分:最常见的模式包含β-2微球蛋白(B2M,m/z = 11,732)以及在m/z = 10,350、9480、4337和4180处的一个或多个峰。模式2缺乏β-2微球蛋白,但包含α-1抗胰蛋白酶的几种降解产物。其他病理成分包括尿蛋白1(m/z = 15,835)、转甲状腺素蛋白(m/z = 13,880)以及在m/z = 13,350处的一种成分。
急性排斥反应患者的检测结果范围从肾脏供体的情况到晚期肾脏疾病的情况不等。这些模式范围可能有助于分析无并发症的移植患者以及移植前后患有进展性肾脏疾病的患者。