Increased Incidence of Angioedema with ACE Inhibitors in Combination with MTOR Inhibitors in Kidney Transplant Recipients

Overview

Journal Clin J Am Soc Nephrol

Specialty Nephrology

Date 2010 Jan 23

PMID 20093343

Citations 32

Authors

Michael Duerr

Petra Glander

Fritz Diekmann

Duska Dragun

Hans-H Neumayer

Klemens Budde

Affiliations

Soon will be listed here.

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.

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References

Stallone G, Infante B, Di Paolo S, Schena A, Grandaliano G, Gesualdo L . Sirolimus and angiotensin-converting enzyme inhibitors together induce tongue oedema in renal transplant recipients. Nephrol Dial Transplant. 2004; 19(11):2906-8. DOI: 10.1093/ndt/gfh352. View

Gabb G, Ryan P, Wing L, Hutchinson K . Epidemiological study of angioedema and ACE inhibitors. Aust N Z J Med. 1996; 26(6):777-82. DOI: 10.1111/j.1445-5994.1996.tb00624.x. View

Ajayi A, Adigun A . Angioedema and cough in Nigerian patients receiving ACE inhibitors. Br J Clin Pharmacol. 2000; 50(1):81-2. PMC: 2014970. DOI: 10.1046/j.1365-2125.2000.00207.x. View

Fritsche L, Horstrup J, Budde K, Reinke P, Giessing M, Tullius S . Old-for-old kidney allocation allows successful expansion of the donor and recipient pool. Am J Transplant. 2003; 3(11):1434-9. DOI: 10.1046/j.1600-6135.2003.00251.x. View

Cicardi M, Zingale L, Bergamaschini L, Agostoni A . Angioedema associated with angiotensin-converting enzyme inhibitor use: outcome after switching to a different treatment. Arch Intern Med. 2004; 164(8):910-3. DOI: 10.1001/archinte.164.8.910. View

Campbell D, Krum H, Esler M . Losartan increases bradykinin levels in hypertensive humans. Circulation. 2005; 111(3):315-20. DOI: 10.1161/01.CIR.0000153269.07762.3B. View

Yusuf S, Teo K, Pogue J, Dyal L, Copland I, Schumacher H . Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008; 358(15):1547-59. DOI: 10.1056/NEJMoa0801317. View

Fuchs U, Zittermann A, Berthold H, Tenderich G, Deyerling K, Minami K . Immunosuppressive therapy with everolimus can be associated with potentially life-threatening lingual angioedema. Transplantation. 2005; 79(8):981-3. DOI: 10.1097/00007890-200504270-00020. View

Brown N, Ray W, Snowden M, Griffin M . Black Americans have an increased rate of angiotensin converting enzyme inhibitor-associated angioedema. Clin Pharmacol Ther. 1996; 60(1):8-13. DOI: 10.1016/S0009-9236(96)90161-7. View

10.

Zuraw B . Clinical practice. Hereditary angioedema. N Engl J Med. 2008; 359(10):1027-36. DOI: 10.1056/NEJMcp0803977. View

11.

Jeanmart H, Malo O, Carrier M, Nickner C, Desjardins N, Perrault L . Comparative study of cyclosporine and tacrolimus vs newer immunosuppressants mycophenolate mofetil and rapamycin on coronary endothelial function. J Heart Lung Transplant. 2002; 21(9):990-8. DOI: 10.1016/s1053-2498(02)00429-1. View

12.

Mahe E, Morelon E, Lechaton S, Kreis H, de Prost Y, Bodemer C . Angioedema in renal transplant recipients on sirolimus. Dermatology. 2007; 214(3):205-9. DOI: 10.1159/000099584. View

13.

Burdese M, Rossetti M, Guarena C, Consiglio V, Mezza E, Soragna G . Sirolimus and ACE-inhibitors: a note of caution. Transplantation. 2005; 79(2):251-2. DOI: 10.1097/01.tp.0000140966.13047.85. View

14.

Ulmer J, Garvey M . Fatal angioedema associated with lisinopril. Ann Pharmacother. 1992; 26(10):1245-6. DOI: 10.1177/106002809202601012. View

15.

Vleeming W, Van Amsterdam J, Stricker B, de Wildt D . ACE inhibitor-induced angioedema. Incidence, prevention and management. Drug Saf. 1998; 18(3):171-88. DOI: 10.2165/00002018-199818030-00003. View

16.

Bas M, Adams V, Suvorava T, Niehues T, Hoffmann T, Kojda G . Nonallergic angioedema: role of bradykinin. Allergy. 2007; 62(8):842-56. DOI: 10.1111/j.1398-9995.2007.01427.x. View

17.

DONALDSON V, Evans R . A BIOCHEMICAL ABNORMALITY IN HEREDIATRY ANGIONEUROTIC EDEMA: ABSENCE OF SERUM INHIBITOR OF C' 1-ESTERASE. Am J Med. 1963; 35:37-44. DOI: 10.1016/0002-9343(63)90162-1. View

18.

Kostis J, Kim H, Rusnak J, Casale T, Kaplan A, Corren J . Incidence and characteristics of angioedema associated with enalapril. Arch Intern Med. 2005; 165(14):1637-42. DOI: 10.1001/archinte.165.14.1637. View

19.

Wadei H, Gruber S, El-Amm J, Garnick J, West M, Granger D . Sirolimus-induced angioedema. Am J Transplant. 2004; 4(6):1002-5. DOI: 10.1111/j.1600-6143.2004.00429.x. View

20.

Schiller P, Messmer S, Haefeli W, Schlienger R, Bircher A . Angiotensin-converting enzyme inhibitor-induced angioedema: late onset, irregular course, and potential role of triggers. Allergy. 1997; 52(4):432-5. DOI: 10.1111/j.1398-9995.1997.tb01024.x. View