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

• Published in: International journal of colorectal disease Vol. 18; no. 5; pp. 406 - 412
• Main Authors: Dehmer, Carsten, Greinwald, Roland, Löffler, Juergen, Grotz, Wolfgang, Wolf, Lothar, Hagmann, Hans-Burkhardt, Schneider, Werner, Kreisel, Wolfgang
• Format: Journal Article
• Language: English
• Published: Germany Springer Nature B.V 01-09-2003
• Subjects: Adult; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; beta-N-Acetyl-Galactosaminidase; Biomarkers - blood; Biomarkers - urine; Crohn Disease - drug therapy; Crohn Disease - enzymology; Crohn Disease - immunology; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hexosaminidases - urine; Humans; Kidney Tubules - drug effects; Male; Mesalamine - administration & dosage; Prospective Studies; Receptors, Interleukin-2 - blood; Receptors, Tumor Necrosis Factor - blood
• ISSN: 0179-1958; 1432-1262
• DOI: 10.1007/s00384-002-0467-7

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.