Dehmer Carsten, Greinwald Roland, Löffler Juergen, Grotz Wolfgang, Wolf Lothar, Hagmann Hans-Burkhardt, Schneider Werner, Kreisel Wolfgang
Department of Gastroenterology, Hepatology and Endocrinology, Medical Clinic, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany.
Int J Colorectal Dis. 2003 Sep;18(5):406-12. doi: 10.1007/s00384-002-0467-7. Epub 2003 Feb 8.
Elevated levels of renal tubular markers in the urine are found in 20-30% of patients with chronic inflammatory bowel diseases. We investigated whether this reflects a dose-dependent tubulotoxicity of 5-aminosalicylic acid (5-ASA).
In an open, prospective, multicenter study 18 patients with Crohn's disease and 29 with ulcerative colitis were treated with 3 g 5-ASA or more daily as the sole drug for 6 weeks. Clinical activity (CDAI, CAI) and renal tubular markers [beta-N-acetyl-D-glucosaminidase (beta-NAG) and other proteins in urine] were monitored. We examined whether the proportion of patients with elevated beta-NAG is more than 15% higher (absolute difference) than that prior to treatment.
The proportion decreased from 19.2% to 12.8% in the intention-to-treat analysis (n=47) and from 24.3% to 13.5% in the per-protocol analysis (n=37), which was not more than 15% higher than at baseline. Mean CDAI decreased from 222 to 146 and mean CAI from 7.3 to 3.1 (intention-to-treat analysis). Response to therapy was shown by 61% of patients with Crohn's disease and 66% of patients with ulcerative colitis. The cumulative dose of 5-ASA was not correlated with beta-NAG level in the urine.
This study largely rules out that 5-ASA at 3 g or higher per day for 6 weeks induces renal tubular damage. Elevated renal tubular markers reflect inflammatory activity or an extraintestinal manifestation of inflammatory bowel diseases.
在20%至30%的慢性炎症性肠病患者尿液中发现肾小管标志物水平升高。我们研究了这是否反映了5-氨基水杨酸（5-ASA）的剂量依赖性肾小管毒性。
在一项开放、前瞻性、多中心研究中，18例克罗恩病患者和29例溃疡性结肠炎患者每天接受3克或更多的5-ASA作为唯一药物治疗6周。监测临床活动度（CDAI、CAI）和肾小管标志物[β-N-乙酰-D-葡萄糖苷酶（β-NAG）及尿液中的其他蛋白质]。我们检查了β-NAG升高的患者比例是否比治疗前高出15%以上（绝对差异）。
在意向性分析（n = 47）中，该比例从19.2%降至12.8%，在符合方案分析（n = 37）中从24.3%降至13.5%，均未比基线高出15%以上。在意向性分析中，平均CDAI从222降至146，平均CAI从7.3降至3.1。61%的克罗恩病患者和66%的溃疡性结肠炎患者显示对治疗有反应。5-ASA的累积剂量与尿液中β-NAG水平无关。
本研究在很大程度上排除了每天3克或更高剂量的5-ASA持续6周会导致肾小管损伤。肾小管标志物升高反映了炎症活动或炎症性肠病的肠外表现。
