Use of mTOR inhibitors in chronic heart transplant recipients with renal failure: Calcineurin-inhibitors conversion or minimization?

Abstract Background In the last decade, mTOR inhibitors (mTOR-is) have become the cornerstone of the calcineurin inhibitor (CNI)-reduced/free regimens aimed to the preservation of post-transplant renal function. We compared utility and safety of the total replacement of calcineurin inhibitors with a...

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Published in:International journal of cardiology 2014-01, Vol.171 (1), p.15-23
Main Authors: Gonzalez-Vilchez, F, Vazquez de Prada, J.A, Paniagua, M.J, Gomez-Bueno, M, Arizon, J.M, Almenar, L, Roig, E, Delgado, J, Lambert, J.L, Perez-Villa, F, Sanz-Julve, M.L, Crespo-Leiro, M, Segovia, J, Lopez-Granados, A, Martinez-Dolz, L, Mirabet, S, Escribano, P, Diaz-Molina, B, Farrero, M, Blasco, T
Format: Article
Language:English
Subjects:
Aged
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Biological and medical sciences
Calcineurin - metabolism
Calcineurin Inhibitors
Cardiac transplantation
Cardiology. Vascular system
Cardiovascular
Cohort Studies
Drug Substitution - trends
Everolimus
Female
Follow-Up Studies
Heart
Heart Transplantation - trends
Humans
Immunosuppression
Immunosuppressive Agents - pharmacology
Immunosuppressive Agents - therapeutic use
Male
Medical sciences
Middle Aged
Nephrology. Urinary tract diseases
Nephropathies. Renovascular diseases. Renal failure
Pharmacology. Drug treatments
Renal failure
Renal function
Renal Insufficiency - drug therapy
Renal Insufficiency - metabolism
Renal Insufficiency - surgery
Retrospective Studies
Sirolimus
Sirolimus - analogs & derivatives
Sirolimus - pharmacology
Sirolimus - therapeutic use
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Surgery of the heart
TOR Serine-Threonine Kinases - antagonists & inhibitors
TOR Serine-Threonine Kinases - metabolism
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Summary:Abstract Background In the last decade, mTOR inhibitors (mTOR-is) have become the cornerstone of the calcineurin inhibitor (CNI)-reduced/free regimens aimed to the preservation of post-transplant renal function. We compared utility and safety of the total replacement of calcineurin inhibitors with a mTOR-i with a strategy based on calcineurin inhibitor minimization and concomitant use of m-TOR-i. Methods In a retrospective multi-center cohort of 394 maintenance cardiac recipients with renal failure (GFR < 60 mL/min/1.73 m2 ), we compared 235 patients in whom CNI was replaced with a mTOR-i (sirolimus or everolimus) with 159 patients in whom mTOR-is were used to minimize CNIs. A propensity score analysis was carried out to balance between group differences. Results Overall, after a median time of 2 years from mTOR-i initiation, between group differences for the evolution of renal function were not observed. In a multivariate adjusted model, improvement of renal function was limited to patients with mTOR-i usage within 5 years after transplantation, particularly with the conversion strategy, and in those patients who could maintain mTOR-i therapy. Significant differences between strategies were not found for mortality, infection and mTOR-i withdrawal due to drug-related adverse events. However, conversion group tended to have a higher acute rejection incidence than the minimization group (p = 0.07). Conclusion In terms of renal benefits, our results support an earlier use of mTOR-is, irrespective of the strategy. The selection of either a conversion or a CNI minimization protocol should be based on the clinical characteristics of the patients, particularly their rejection risk.
ISSN:0167-5273
1874-1754
DOI:10.1016/j.ijcard.2013.11.036