Rapalogs and ACE-I-angioedema

Q: Post-transplant patients are at increased risk of ACE inhibitor-induced angioedema.

A) True

B) False

Answer: A

Post-transplant patients who take rapamycin (mTOR) inhibitors, commonly known as rapalogs such as sirolimus or everolimus, are at increased risk of Angiotensin-converting enzyme (ACE) inhibitor-induced angioedema when both are co-administered. Rapalogs reduce the metabolism of bradykinin. The effect appears to be dose-dependent for rapalog. 

Overall, all transplant patients are at increased risk of ACE inhibitor-induced angioedema because immunosuppressants decrease dipeptidyl peptidase 4 (DPP-4) levels, which is responsible for breaking down bradykinin, a key culprit in ACE inhibitor-related angioedema.

#toxicity

#pharmacology

#transplantation

References:

1. Duerr M, Glander P, Diekmann F, et al. Increased incidence of angioedema with ACE inhibitors in combination with mTOR inhibitors in kidney transplant recipients. Clin J Am Soc Nephrol 2010; 5:703.

2. Charmillon A, Deibener J, Kaminsky P, Louis G. Angioedema induced by angiotensin converting enzyme inhibitors, potentiated by m-TOR inhibitors: successful treatment with icatibant. Intensive Care Med 2014; 40:893.

3. Fuchs U, Zittermann A, Berthold HK, et al. Immunosuppressive therapy with everolimus can be associated with potentially life-threatening lingual angioedema. Transplantation 2005; 79:981.

4. Scott SI, Andersen MF, Aagaard L, Buchwald CV, Rasmussen ER. Dipeptidyl Peptidase-4 Inhibitor Induced Angioedema - An Overlooked Adverse Drug Reaction? Curr Diabetes Rev. 2018;14(4):327-333. doi: 10.2174/1573399813666170214113856. PMID: 28201967.