Increased incidence of angioedema with ACE inhibitors in combination with mTOR inhibitors in kidney transplant recipients

Clin J Am Soc Nephrol. 2010 Apr;5(4):703-8. doi: 10.2215/CJN.07371009. Epub 2010 Jan 21.

Abstract

Background and objective: The clinical manifestation of angioedema ranges from minor facial edema up to life-threatening swelling of mouth and throat. Hereditary defects, drugs, and food allergies may play a role in the development of angioedema. We systematically investigated the incidence of angioedema in renal allograft recipients treated with mTOR inhibitors (mTORis).

Design, setting, participants, & measurements: All patients in the authors' electronic database who had received mTORis (n = 309) between 2000 and 2008 were identified. Of these, 137 were additionally treated with angiotensin-converting enzyme inhibitors (ACEis).

Results: Nine patients (6.6%, 3.8 per 100 treatment years) developed angioedema after a mean period of 123 days under combined therapy with mTORi and ACEi. Among the remaining 172 patients on mTORi, including 119 patients treated with angiotensin-receptor blockers, only two developed angioedema (1.2%, 0.5 per 100 treatment years, P = 0.01). In patients receiving mycophenolate and ACEi (n = 462), 10 instances of angioedema were found (2.1%, 0.8 per 100 treatment years, P = 0.004).

Conclusions: This systematic investigation demonstrated a noticeable incidence of 6.6% angioedema under combined therapy with mTORi and ACEi in kidney transplant recipients. Treatment with either ACEi or mTORi alone resulted in a significantly lower incidence of angioedema, suggesting that this combination should be avoided.

MeSH terms

  • Adolescent
  • Aged
  • Angioedema / chemically induced*
  • Angioedema / epidemiology
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Chi-Square Distribution
  • Drug Interactions
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Incidence
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • TOR Serine-Threonine Kinases
  • Time Factors
  • Transplantation, Homologous
  • Young Adult

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Immunosuppressive Agents
  • Intracellular Signaling Peptides and Proteins
  • MTOR protein, human
  • Protein Serine-Threonine Kinases
  • TOR Serine-Threonine Kinases