Kreisel W, Wolf L M, Grotz W, Grieshaber M
Albert-Ludwigs-Universität, Abteilung Gastroenterologie, Hepatologie und Endokrinologie, Freiburg, Germany.
Eur J Gastroenterol Hepatol. 1996 May;8(5):461-8.
To investigate whether treatment of inflammatory bowel disease (IBD) with 5-aminosalicylate or sulphasalazine in IBD may induce renal tubular damage.
The urinary enzymes beta-N-acetyl-D-glucosaminidase ( beta-NAG), dipeptidylpeptidase 4 (DPP4) and alanine aminopeptidase (AAP) were measured as markers of renal tubular damage in 104 consecutive patients with Crohn's disease and in 43 consecutive patients with ulcerative colitis (all with normal serum creatinine values). Control values were gained from 65 healthy persons.
The normal values (mean +/- SD) for the urinary enzymes investigated (U/g creatinine in the urine) were: DPP4 4.5 +/- 2.2, beta-NAG 1.6 +/- 1.4, AAP 11.4 +/- 6.5. In 28% of the patients with ulcerative colitis elevated beta-NAG levels of more than the mean + 2 x SD were measured. This pathological enzymuria was nearly exclusively found in patients with active disease (CAI > 6): DPP4 15.6 +/- 25.3, beta-NAG 8.3 +/- 10.1, AAP 24.7 +/- 50.1 (all three enzymes were significantly elevated). The highest values were measured in patients with active ulcerative colitis before start of therapy. Nineteen per cent of the patients with Crohn's disease had elevated beta-NAG levels of more than the mean + 2 x SD. There was no significant difference in enzymuria between patients with active (CDAI > 150) and patients with inactive Crohn's disease (CDAI < or = 150). DPP4 and AAP were normal in both groups. A correlation between the enzymuria and the cumulative doses of 5-aminosalicylic acid, sulphasalazine or prednisolone could not be found. The courses of enzymuria in three patients who presented with the first severe manifestation of IBD are described. They were treated with either corticosteroids and 5-aminosalicylic acid or corticosteroids and sulphasalazine. Before onset of therapy, very high urine enzyme values were measured. They almost normalized in the course of successful medical therapy despite increasing cumulative doses of 5-aminosalicylic acid or sulphasalazine.
Renal tubular damage can frequently be observed in IBD. Our results suggest that this is an extraintestinal manifestation of the disease and not a toxic side-effect of anti-inflammatory therapy using 5-aminosalicylic acid or sulphasalazine.
研究炎症性肠病（IBD）患者使用5-氨基水杨酸或柳氮磺胺吡啶治疗是否会导致肾小管损伤。
测定104例克罗恩病患者和43例溃疡性结肠炎患者（所有患者血清肌酐值均正常）的尿酶β-N-乙酰-D-氨基葡萄糖苷酶（β-NAG）、二肽基肽酶4（DPP4）和丙氨酸氨基肽酶（AAP），作为肾小管损伤的标志物。对照组为65名健康人。
所研究尿酶的正常值（尿中U/g肌酐，均值±标准差）为：DPP4 4.5±2.2，β-NAG 1.6±1.4，AAP 11.4±6.5。28%的溃疡性结肠炎患者β-NAG水平高于均值+2×标准差。这种病理性酶尿几乎仅见于活动期患者（临床活动指数>6）：DPP4 15.6±25.3，β-NAG 8.3±10.1，AAP 24.7±50.1（所有三种酶均显著升高）。治疗开始前，活动期溃疡性结肠炎患者的酶值最高。19%的克罗恩病患者β-NAG水平高于均值+2×标准差。活动期克罗恩病患者（临床疾病活动指数>150）与非活动期克罗恩病患者（临床疾病活动指数≤150）之间的酶尿无显著差异。两组患者的DPP4和AAP均正常。未发现酶尿与5-氨基水杨酸、柳氮磺胺吡啶或泼尼松龙的累积剂量之间存在相关性。描述了3例首次出现IBD严重表现患者的酶尿病程。他们接受了糖皮质激素和5-氨基水杨酸或糖皮质激素和柳氮磺胺吡啶治疗。治疗开始前，尿酶值非常高。尽管5-氨基水杨酸或柳氮磺胺吡啶的累积剂量增加，但在成功的药物治疗过程中，酶值几乎恢复正常。
IBD患者中经常可观察到肾小管损伤。我们的结果表明，这是该疾病的一种肠外表现，而非使用5-氨基水杨酸或柳氮磺胺吡啶进行抗炎治疗的毒性副作用。
