Correspondence
Everolimus in Cardiac-Transplant Recipients
N Engl J Med 2003; 349:2271-2272December 4, 2003
- Article
To the Editor:
Eisen et al. (Aug. 28 issue)1 report less severe rejection and less intimal thickening in cardiac-transplant recipients who received everolimus than in those who received azathioprine. However, we are concerned about the marked and sustained impairment of renal function in patients treated with everolimus and full-dose cyclosporine; the mean creatinine concentration at the last measurement during treatment in the two everolimus groups was 2.15 mg per deciliter, as compared with 1.71 mg per deciliter in the azathioprine group, corresponding to a difference of approximately 11 ml per minute in estimated creatinine clearance. Renal impairment after cardiac transplantation is a frequent complication (the average creatinine concentration increases from approximately 0.9 mg per deciliter to nearly 1.8 mg per deciliter at two years, and chronic renal failure develops in approximately 12 percent of cardiac-transplant recipients at five years2,3) and is associated with markedly decreased long-term survival among patients.3-5 It would be of great interest to know whether patients in the present trial progressed to end-stage renal disease and in how many severe chronic renal failure developed.
5 ReferencesBernhard Banas, M.D.
Carsten Böger, M.D.
Bernhard Krämer, M.D.
Klinikum der Universität Regensburg, 93042 Regensburg, Germany
bernhard.kraemer@klinik. uni-regensburg. de 1
Eisen HJ ,Tuzcu EM ,Dorent R , et al. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med 2003;349:847-858
Full Text | Web of Science | Medline2
Herlitz H ,Lindelow B . Renal failure following cardiac transplantation. Nephrol Dial Transplant 2000;15:311-314
CrossRef | Web of Science | Medline3
Ojo AO ,Held PJ ,Port FK , et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 2003;349:931-940
Full Text | Web of Science | Medline4
van Gelder T ,Balk AH ,Zietse R ,Hesse C ,Mochtar B ,Weimar W . Renal insufficiency after heart transplantation: a case-control study. Nephrol Dial Transplant 1998;13:2322-2326
CrossRef | Web of Science | Medline5
Veillon S ,Caillard S ,Epailly E ,Eisenmann B ,Hannedouche T ,Moulin B . Chronic renal failure after cardiac transplantation: predictive factors and influence on mortality -- results of a monocenter study in 141 patients. Transplant Proc 2002;34:2819-2820
CrossRef | Web of Science | Medline
Author/Editor Response
Dr. Banas and colleagues raise the important issue of renal impairment in patients receiving everolimus and full-dose cyclosporine. This was reflected in the elevation in the mean creatinine concentration in the study groups that received everolimus (2.15 mg per deciliter), as compared with the azathioprine group (1.71 mg per deciliter). This clinical observation appears to be the result of an interaction between the calcineurin antagonists and the mTOR inhibitors. The progression of the patients to end-stage renal failure in our trial would therefore be of particular importance in the light of the diminished survival of cardiac-transplant recipients in whom end-stage renal disease or severe chronic renal failure develops.1,2
After 24 months of follow-up, 8 of 209 patients in the 1.5-mg everolimus group (3.8 percent) had chronic renal failure, as did 8 of 211 in the 3.0-mg everolimus group (3.8 percent). In contrast, 2 of 214 patients in the azathioprine group (0.9 percent) had chronic renal failure. One of the eight patients in the 1.5-mg everolimus group who had chronic renal failure underwent renal transplantation. The incidence of chronic renal failure in the two everolimus groups, although elevated as compared with that in the azathioprine group, does not appear to be higher than that reported at 24 months in a recent study.1 Furthermore, there was improvement in renal function in the patients in our study whose cyclosporine doses were reduced, so that the target trough level was 100 ng per deciliter, as part of an amendment introduced during the trial. Future efforts will need to address the issue of the optimal cyclosporine dosage in patients receiving everolimus; reductions in target cyclosporine doses early after transplantation will probably be included.
2 ReferencesHoward J. Eisen, M.D.
Temple University School of Medicine, Philadelphia, PA 19140
eisenh@tuhs.temple. edu for the RAD B253 Study Group
1
Ojo AO ,Held PJ ,Port FK , et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 2003;349:931-940
Full Text | Web of Science | Medline2
Veillon S ,Caillard S ,Epailly E ,Eisenmann B ,Hannedouche T ,Moulin B . Chronic renal failure after cardiac transplantation: predictive factors and influence on mortality -- results of a monocenter study in 141 patients. Transplant Proc 2002;34:2819-2820
CrossRef | Web of Science | Medline
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