No dose-dependent tubulotoxicity of 5-aminosalicylic acid: a prospective study in patients with inflammatory bowel diseases.

Background And Aims: 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).

Patients And Methods: 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.

Results: 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.

Conclusion: 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.