Division of Gastroenterology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
J Clin Gastroenterol. 2012 Apr;46(4):308-10. doi: 10.1097/MCG.0b013e31822b80e0.
Citrulline is a nitrogen end product produced from the intermediary metabolism of glutamine through the enzymatically mediated urea cycle, almost exclusively in the enterocytes of small intestinal epithelium, with some synthesis in colonocytes. Intestinal dysfunction resulting from intestinal diseases or injuries affects intermediary metabolism, which includes citrulline synthesis. We sought to determine whether plasma citrulline was a biomarker for disease activity in patients with Crohn's disease with the hypothesis that citrulline concentration would be reduced during active disease.
A total of 81 outpatients aged 18 to 65 years (mean, 40.6±15.4 y) with a known history of Crohn's disease were studied prospectively. Patients with prior small intestinal resection, or renal or hepatic insufficiency were excluded. Crohn's disease activity was measured by Harvey-Bradshaw Index (HBI) and was correlated to the plasma citrulline concentration measured simultaneously (ion chromatography). Spearman correlation coefficients were used to assess for an association between the 2 variables. Subgroup analyses of patients with isolated small intestinal disease and endoscopically or radiologic verified disease activity were also performed.
Twenty-two patients had isolated colonic disease and 59 had small intestinal involvement. Twenty-six of these patients had concurrent endoscopy and/or computed tomography or magnetic resonance imaging. On the basis of HBI scores, 32 patients had active disease (HBI ≥5) and 49 patients had inactive disease. The mean HBI scores were 4.8±5.5. The mean plasma citrulline concentration was normal, although was below normal in some patients. However, it failed to distinguish between active and inactive patients based on the HBI (active 27.8±8.8 μmol/L, inactive 27.8±11.1 μmol/L, P=0.991). There was no significant linear association between the ranks of citrulline and ranks of HBI (rs=0.012, P=0.915). Of the 59 patients with isolated small intestinal disease, there was no association between plasma citrulline concentration and the HBI (Spearman correlation coefficient, 0.073; P=0.583). There was no difference in plasma citrulline concentrations among those with confirmed inflammation by imaging or endoscopy (confirmed, 26.2±11.8; negative, 28.0±10.0; independent t test P=0.583).
Plasma citrulline concentration was not a marker of disease activity in patients with Crohn's disease. However, all patients studied were outpatients and it is possible that plasma citrulline concentration may be depressed only in patients with more severe disease or extensive small bowel involvement. In addition, plasma citrulline may be increased in the postabsorptional state, and for the most part, our patients were nonfasting. More studies are needed to further elucidate the role of citrulline as a marker of disease activity in patients with Crohn's disease. The possibility also exists that citrulline may be a better marker in patients with previous resection, and this group will require specific evaluation.
瓜氨酸是一种氮的终产物，通过酶介导的尿素循环从中间代谢物谷氨酰胺产生，几乎仅在小肠上皮的肠细胞中产生，一些在结肠细胞中合成。肠道疾病或损伤导致的肠道功能障碍会影响中间代谢物，包括瓜氨酸的合成。我们试图确定血浆瓜氨酸是否是克罗恩病患者疾病活动的生物标志物，假设在疾病活动期瓜氨酸浓度会降低。
我们前瞻性地研究了 81 名年龄在 18 至 65 岁（平均 40.6±15.4 岁）之间的已知克罗恩病病史的门诊患者。排除了有小肠切除术史、肾功能或肝功能不全的患者。通过 Harvey-Bradshaw 指数（HBI）测量克罗恩病的活动度，并同时（离子色谱法）测量血浆瓜氨酸浓度。使用 Spearman 相关系数评估两个变量之间的关联。还对仅累及小肠和内镜或放射学确认的疾病活动的患者进行了亚组分析。
22 例患者为单纯结肠疾病，59 例患者为小肠受累。其中 26 例患者同时进行了内镜和/或计算机断层扫描或磁共振成像检查。根据 HBI 评分，32 例患者为活动期疾病（HBI≥5），49 例患者为非活动期疾病。HBI 评分平均为 4.8±5.5。平均血浆瓜氨酸浓度正常，但有些患者的浓度低于正常水平。然而，根据 HBI 评分，它无法区分活动期和非活动期患者（活动期 27.8±8.8 μmol/L，非活动期 27.8±11.1 μmol/L，P=0.991）。瓜氨酸等级与 HBI 等级之间没有显著的线性关联（rs=0.012，P=0.915）。在 59 例仅累及小肠的患者中，血浆瓜氨酸浓度与 HBI 之间无相关性（Spearman 相关系数为 0.073，P=0.583）。经影像学或内镜证实有炎症的患者的血浆瓜氨酸浓度无差异（证实，26.2±11.8；阴性，28.0±10.0；独立 t 检验，P=0.583）。
在克罗恩病患者中，血浆瓜氨酸浓度不是疾病活动的标志物。然而，所有研究的患者都是门诊患者，可能只有病情更严重或小肠受累广泛的患者血浆瓜氨酸浓度才会降低。此外，血浆瓜氨酸可能在吸收后增加，而且我们的大部分患者都没有禁食。需要进一步的研究来阐明瓜氨酸作为克罗恩病患者疾病活动标志物的作用。瓜氨酸可能是以前有过切除手术的患者的一个更好的标志物，而这一群体需要特定的评估。
