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

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Abstract

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 [β-N-acetyl-d-glucosaminidase (β-NAG) and other proteins in urine] were monitored. We examined whether the proportion of patients with elevated β-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 β-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.

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Acknowledgements

Financial support for this trial was provided by Dr. Falk Pharma GmbH (Freiburg, Germany). We are grateful to Wolfgang Moessner for his excellent technical assistance. The members of the German Salofalk Study Group are the following: Participating investigators: W. Kreisel (principal investigator), C. Dehmer, W. Grotz, W. Koester, Medical Clinic, University of Freiburg, Freiburg; J. Schoelmerich (principal investigator), T. Andus, Medical Clinic, University of Regensburg, Regensburg; H.J. Kramm, private practice, Berlin; L. Wolf, M. Staritz (principal investigator), Hospital Schwenningen, Villingen-Schwenningen; H. Hagmann, private practice, Berlin; J. Schenk, private practice, Erlangen; G. Wolf, private practice, Cologne; A. Brom, private practice, Klinik Oberwald, Grebenhain; E. Hommel, private practice, Stuttgart; C. Struckmeyer, private practice, Gehrden; W. Schneider, private practice, Halle. Industry participant: Dr. Falk Pharma GmbH, Freiburg, R. Greinwald. Biometric planning and evaluation: medicomp GmbH, Planegg-Martinsried, M. Gierend, J. Loeffler, T. Plassmann.

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Authors and Affiliations

  1. Department of Gastroenterology, Hepatology and Endocrinology, Medical Clinic, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany

    Carsten Dehmer & Wolfgang Kreisel

  2. Dr. Falk Pharma GmbH, Leinenweberstrasse 5, 79041 , Freiburg, Germany

    Roland Greinwald

  3. medicomp GmbH, Lochhamer Strasse 11, 82152, Planegg-Martinsried, Germany

    Juergen Löffler

  4. Department of Nephrology, Medical Clinic, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany

    Wolfgang Grotz

  5. Medizinische Klinik Schwenningen, Roentgenstrasse 20, 78054, Villingen-Schwenningen, Germany

    Lothar Wolf

  6. Heilmannring 74, 13627, Berlin, Germany

    Hans-Burkhardt Hagmann

  7. Grosse Steinstrasse 32, 06108, Halle, Germany

    Werner Schneider

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  1. Carsten Dehmer
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  2. Roland Greinwald
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  3. Juergen Löffler
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  4. Wolfgang Grotz
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  6. Hans-Burkhardt Hagmann
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  7. Werner Schneider
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  8. Wolfgang Kreisel
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and the German Salofalk® Study Group

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Correspondence to Wolfgang Kreisel.

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Dehmer, C., Greinwald, R., Löffler, J. et al. No dose-dependent tubulotoxicity of 5-aminosalicylic acid: a prospective study in patients with inflammatory bowel diseases. Int J Colorectal Dis 18, 406–412 (2003). https://doi.org/10.1007/s00384-002-0467-7

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  • DOI: https://doi.org/10.1007/s00384-002-0467-7

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