title: No dose-dependent tubulotoxicity of 5-aminosalicylic acid: a prospective study in patients with inflammatory bowel diseases.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medical Clinic, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Dehmer
authors.forename: Roland
authors.initials: R
authors.lastname: Greinwald
authors.forename: Juergen
authors.initials: J
authors.lastname: Löffler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Grotz
authors.forename: Lothar
authors.initials: L
authors.lastname: Wolf
authors.forename: Hans-Burkhardt
authors.initials: HB
authors.lastname: Hagmann
authors.forename: Werner
authors.initials: W
authors.lastname: Schneider
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kreisel
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003424:Crohn Disease / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006596:Hexosaminidases / Q000652:urine*; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects*; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage*; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D048828:beta-N-Acetyl-Galactosaminidase
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D015375:Receptors, Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D019804:Mesalamine; D006596:Hexosaminidases; D048828:beta-N-Acetyl-Galactosaminidase