Drug-induced nephrolithiasis and crystalluria: the particular case of the sulfasalazine derivatives

Introduction: Drug-induced calculi are rarely reported in literature but represent a seldom reported complication of long-term or high-dose prescription of certain medications. We review here some drugs involved in stone formation from first case reports of sulfonamides in the 1930s to protease inhibitors and sulfadiazine with more recent emergence of HIV and opportunistic infections. Finally, we will study in particular sulfasalazine and mesalazine, two different forms of a drug used for treatment of ulcerative colitis or Crohn's disease. Material and methods: Review of the literature and report of a series of ten new cases of mesalazine-induced nephrolithiasis. Results and discussion: Ten patients (eight women and two men) produced stones spontaneously passed (n = 9) or surgically removed (n = 1). Patients received mesalazine either for ulcerative colitis (n = 6) or Crohn's disease (n = 4). The daily oral dose was 4 g/d in nine patients and only 2 g/d in one subject. The duration of medication before stone episode ranged from one month up to 15 years with an average of four years. Stone analysis found pure mesalazine in all stones analyzed (n = 9). Rod-shaped crystals found in urine of one patient (stone unavailable) were identified as mesalazine by Fourier transform infrared spectroscopy. Conclusion: We report the largest case-series of mesalazine nephrolithiasis, and the first case of mesalazine crystalluria to date. Nonmetabolized mesalazine composition of concretions suggests peculiar drug absorption and/or metabolism in these patients. Of note, women seem to be more affected by this side effect.