Incidence of Cyclophosphamide-induced Urotoxicity and Protective Effect of Mesna in Rheumatic Diseases

J Rheumatol. 2015 Sep;42(9):1661-6. doi: 10.3899/jrheum.150065. Epub 2015 Jul 15.


Objective: To assess bladder toxicity of cyclophosphamide (CYC) and uroprotective effect of mesna in rheumatic diseases.

Methods: Data of 1018 patients (725 women/293 men) treated with CYC were evaluated in this retrospective study. All of the following information was obtained: the cumulative CYC dose, route of CYC administration, duration of therapy, concomitant mesna usage, and hemorrhagic cystitis. Cox proportional hazard model was used for statistics.

Results: We identified 17 patients (1.67%) with hemorrhagic cystitis and 2 patients (0.19%) with bladder cancer in 4224 patient-years. The median time for diagnosis to hemorrhagic cystitis was 10 months (4-48) and bladder cancer was 8 years (6-10.9). There were 583 patients (57.2%) who received mesna with intravenous CYC therapy. We observed similar incidence rate for hemorrhagic cystitis in both patient groups concomitantly treated with or without mesna [9/583 (1.5%) vs 8/425 (1.8%) respectively, p = 0.08]. Cumulative CYC dose (HR for 10-g increments 1.24, p < 0.001) was associated with hemorrhagic cystitis.

Conclusion: Cumulative dose was the only risk factor for hemorrhagic cystitis in patients treated with CYC. No proof was obtained for the uroprotective effect of mesna in our cohort.


MeSH terms

  • Adult
  • Aged
  • Cyclophosphamide / adverse effects*
  • Cyclophosphamide / therapeutic use
  • Cystitis / chemically induced
  • Cystitis / epidemiology*
  • Female
  • Humans
  • Incidence
  • Male
  • Mesna / therapeutic use*
  • Middle Aged
  • Protective Agents / therapeutic use*
  • Rheumatic Diseases / drug therapy*
  • Treatment Outcome


  • Protective Agents
  • Cyclophosphamide
  • Mesna