Division of Clinical Pharmacology, Department of Pharmacology, School of Medicine, Jichi Medical University, Tochigi, 329-0498, Japan.
J Appl Toxicol. 2014 Feb;34(2):184-90. doi: 10.1002/jat.2849. Epub 2013 Jan 11.
Renal complications are often detected in patients with inflammatory bowel disease (IBD). Because conventional markers such as serum creatinine and β2-microglobulin are not sensitive and/or specific, a new renal biomarker is needed. We have recently identified urinary vanin-1 as an early biomarker for the detection of nephrotoxicant-induced renal injury. In this study, we compared the usefulness of urinary vanin-1 with other newly developed biomarkers [urinary monocyte chemoattractant protein-1 (MCP-1), kidney injury molecule-1 (Kim-1) and N-acetyl-beta-D-glucosaminidase (NAG)] for the detection of renal complications in rats with experimental colitis. On day 2 after intracolonic injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), male Wistar rats developed not only colitis, but histologically evident renal injury. Urinary vanin-1 started to elevate on day 1, whereas serum creatinine and urinary excretions of glucose, total protein, albumin, Kim-1, MCP-1 and NAG significantly increased only on day 2. The mRNA expressions of vanin-1 and Kim-1 significantly increased in the kidney, but not in the colon. In addition, vanin-1 did not appear in the blood. On the other hand, colonic mRNA expression and the serum concentration of MCP-1 were significantly higher in the TNBS-treated rats than in the control animals. These results suggest that, in contrast to MCP-1, urinary vanin-1 and Kim-1 mainly originated from the kidney rather than the colon in this model. Compared with Kim-1 and MCP-1, vanin-1 might be an earlier biomarker for the detection of renal injury in rats with experimental colitis.
肾脏并发症在炎症性肠病（IBD）患者中经常被发现。由于血清肌酐和β2-微球蛋白等传统标志物不敏感和/或特异性，因此需要一种新的肾脏生物标志物。我们最近发现尿 vanin-1 是检测肾毒性物质引起的肾损伤的早期生物标志物。在这项研究中，我们比较了尿 vanin-1 与其他新开发的生物标志物[尿单核细胞趋化蛋白-1（MCP-1）、肾损伤分子-1（Kim-1）和 N-乙酰-β-D-氨基葡萄糖苷酶（NAG）]在检测实验性结肠炎大鼠肾脏并发症中的有用性。在 2,4,6-三硝基苯磺酸（TNBS）经结肠内注射后的第 2 天，雄性 Wistar 大鼠不仅发生了结肠炎，而且还出现了明显的肾组织损伤。尿 vanin-1 于第 1 天开始升高，而血清肌酐和尿葡萄糖、总蛋白、白蛋白、Kim-1、MCP-1 和 NAG 的排泄量仅在第 2 天显著增加。肾中 vanin-1 和 Kim-1 的 mRNA 表达显著增加，但在结肠中没有。此外，vanin-1 并未出现在血液中。另一方面，与对照组相比，TNBS 处理的大鼠结肠 mRNA 表达和血清 MCP-1 浓度显著升高。这些结果表明，与 MCP-1 相比，尿 vanin-1 和 Kim-1 主要来源于该模型中的肾脏而不是结肠。与 Kim-1 和 MCP-1 相比，vanin-1 可能是检测实验性结肠炎大鼠肾损伤的更早的生物标志物。
