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Presenter: Frieder, Keller, Ulm, Germany
Authors: Keller F.
CLINICAL IMMUNOSUPPRESSION - KIDNEY LATE
Internal Medicine, Nephrology, University Hospital, Ulm/GERMANY
The mTOR inhibitor everolimus is used for immunosuppression after kidney transplantation and stem cell transplantation. Everolimus is more hydrophilic, the half-life shorter (31 vs 60 h), and theadverse events might be less frequent as compared to sirolimus [Rehm B, Keller F, Mayer J, Stracke S. Resolution of sirolimus-induced pneumonitis after conversion to everolimus. Transplant Proc. 2006Apr;38(3):711-3.]. We report on our experience with everolimus, and compared the therapeutic effect and adverse events between kidney and stem cell transplant patients.
Patients and Methods
Therapeutic drug monitoring was performed in 162 patients receiving everolimus in our hospital in the years 2007 to 2009. The clinical course retrospectively could be assessed in 122 patients, 76males and 46 females.. Everolimus was given to 81 patients after kidney transplantation and to 41 patients after stem cell transplantation. Everolimus co-medication was mycophenolate in 63 andglucocorticoids in 48 patients. Everolimus was taken for 1 to 51 months with a median of 7 months in kidney and 5 months in stem cell patients.
At start of everolimus, the kidney transplant patients were significantly older (p < 0.01) than stem cell transplant patients (56 +/- 12 vs 47 +/- 11 y). The reason for everolimus was different inkidney transplant patients as compared to stem cell transplant patients, with calcineurin inhibitor toxicity (34 vs 5), graft versus host disease (0 vs 23), secondary malignancies mostly scin (19 vs1) and sirolimus intolerance (15 vs 0). With a median dose of 1.5 mg/d the mean everolimus trough level was 4.9 +/- 1.9 ng/ml after kidney transplantation and 6.4 +/- 2.1 ng/ml after stem celltransplantation (p = 0.01). The mean creatinine significantly improved (p < 0.01) from 284 +/- 161 to 201 +/- 90 mcmol/l but deteriorated again to 266 +/- 135 mcmol/l in the kidney patients, butwas throughout significantly lower with 111 +/- 83 mcmol/l in the stem cell patients. Except death (6 vs 12) and low platelets (4 vs 15), overall adverse events were significantly more frequent inkidney than in stem cell patients such as a urinary protein/creatinine ratio >1.0 g/g (16 vs 2), pneumonitis (4 vs 0), dermatitis (10 vs 0), and infectious complications (14 vs 2). A proteinuria/creatinine ratio of 4.6 and 5.7 g/g, respectively had 2 kidney patients with the nephrotic syndrome occurring 1 and 12 months after everolimus. Everolimus therapy was discontinued in 81 cases (66%)among them because of adverse events in 32 cases (40%), mainly dermatitis (n = 15), infections (n = 10), thrombotic thrombocytopenic purpura (n = 7), proteinuria (n = 12) and pneumonitis (n =4).
Everolimus was a good option in kidney transplant patients with calcineurin inhibitor toxicity or secondary malignancies since serum creatinine improved significantly. However, everolimus had to bediscontinued in 32/122 = 26% of all patients because of adverse events. Importantly, proteinuria and pneumonitis were observed only in kidney transplant patients but not after stem celltransplantation.
Disclosure: All authors have declared no conflicts of interest.
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