Avoidance of Calcineurin Inhibitors With Use of Proliferation Signal Inhibitors in De Novo Heart Transplantation With Renal Failure

• Published in: The Journal of heart and lung transplantation Vol. 27; no. 10; pp. 1135 - 1141
• Main Authors: González-Vílchez, Francisco, MD, Vázquez de Prada, José Antonio, MD, Exṕosito, Víctor, MD, García-Camarero, Tamara, MD, Fernández-Friera, Leticia, MD, Llano, Miguel, MD, Ruano, Javier, MD, Martín-Durán, Rafael, MD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.10.2008; Elsevier Science
• Subjects: Administration, Oral; Adrenal Cortex Hormones - therapeutic use; Azathioprine - therapeutic use; Biological and medical sciences; Calcineurin Inhibitors; Cardiology. Vascular system; Cell Division - drug effects; Everolimus; Glomerular Filtration Rate; Graft Rejection - prevention & control; Heart; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Heart Transplantation - adverse effects; Humans; Immunosuppressive Agents - therapeutic use; Kidney - drug effects; Kidney - pathology; Kidney Function Tests; Medical sciences; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Renal failure; Renal Insufficiency - epidemiology; Retrospective Studies; Sirolimus - administration & dosage; Sirolimus - analogs & derivatives; Sirolimus - therapeutic use; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Kidney disease; Heart; Heart failure; Urinary system disease; Calcineurin inhibitor; Use; Cardiovascular disease; Transplantation; Proliferation; Homotransplantation; Phlebology; De novo; Signal; Treatment; Heart disease; Surgery; Renal failure; Graft; Circulatory system; Cardiology; Avoidance
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2008.07.020

Background This study describes our experience with proliferation signal inhibitors in de novo heart transplant recipients with significant renal impairment. To circumvent further nephrotoxicity, calcineurin inhibitors were avoided in the peri-operative period. Methods Immunosuppression in 20 patients was with a proliferation signal inhibitor (sirolimus, 14; everolimus, 6), an anti-mitotic drug, and corticosteroids from the time of transplantation. Induction was used in 9 patients (45%). All patients had preoperative significant renal dysfunction (mean glomerular filtration rate <30 ml/min/1.73 m2 ), and 4 patients required dialysis. Results Post-operatively, the glomerular filtration rate significantly increased (>65 ml/min/1.73 m2 at Month 1, remaining stable thereafter). No patients required dialysis after the first month of transplantation. Mean follow-up was 500 days. Rejection episodes occurred in 11 patients (55%), and 4 patients died (2 of rejection, although 1 death occurred 48 days after conversion to conventional treatment with tacrolimus). Half of the patients were eventually converted to conventional calcineurin-inhibitor therapy because of proliferation signal inhibitor adverse events. Conclusion Although this immunosuppressive approach was associated with a somewhat high rate of rejection and frequent side effects, it represents an attractive alternative in the complicated peri-operative setting of patients with significant renal impairment. This approach could serve as a temporary bridge to a conventional treatment.