Everolimus With Reduced Calcineurin Inhibitor in Thoracic Transplant Recipients With Renal Dysfunction: A Multicenter, Randomized Trial
2010 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 89, no 7, 864-872 p.Article in journal (Refereed) Published
Background. The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking. Methods. In a 12-month, open-labeled, multicenter study, maintenance thoracic transplant patients (glomerular filtration rate greater than= 20 mL/min/1.73m(2) and less than90 mL/min/1.73 m(2)) greater than1 year posttransplant were randomized to continue their current CNI-based immunosuppression or start everolimus with predefined CNI exposure reduction. Results. Two hundred eighty-two patients were randomized (140 everolimus, 142 controls; 190 heart, 92 lung transplants). From baseline to month 12, mean cyclosporine and tacrolimus trough levels in the everolimus cohort decreased by 57% and 56%, respectively. The primary endpoint, mean change in measured glomerular filtration rate from baseline to month 12, was 4.6 mL/min with everolimus and -0.5 mL/min in controls (Pless than0.0001). Everolimus-treated heart and lung transplant patients in the lowest tertile for time posttransplant exhibited mean increases of 7.8 mL/min and 4.9 mL/min, respectively. Biopsy-proven treated acute rejection occurred in six everolimus and four control heart transplant patients (P=0.54). In total, 138 everolimus patients (98.6%) and 127 control patients (89.4%) experienced one or more adverse event (P=0.002). Serious adverse events occurred in 66 everolimus patients (46.8%) and 44 controls (31.0%) (P=0.02). Conclusion. Introduction of everolimus with CNI reduction offers a significant improvement in renal function in maintenance heart and lung transplant recipients. The greatest benefit is observed in patients with a shorter time since transplantation.
Place, publisher, year, edition, pages
Williams and Wilkins , 2010. Vol. 89, no 7, 864-872 p.
Everolimus; Certican; CNI; Cyclosporine; Tacrolimus; Renal Impairment
National CategoryMedical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-58406DOI: 10.1097/TP.0b013e3181cbac2dISI: 000276807100015OAI: oai:DiVA.org:liu-58406DiVA: diva2:343224