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


METHODS
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.
Duerr
Michael
M
Department of Nephrology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. michael.duerr@charite.de
Glander
Petra
P
Diekmann
Fritz
F
Dragun
Duska
D
Neumayer
Hans-H
HH
Budde
Klemens
K
D000293:Adolescent; D000368:Aged; D000799:Angioedema / Q000139:chemically induced* / Q000453:epidemiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D016009:Chi-Square Distribution; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors; D014184:Transplantation, Homologous; D055815:Young Adult
D000806:Angiotensin-Converting Enzyme Inhibitors; D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases