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NDT Advance Access published online on June 20, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn332
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Conversion to sirolimus for chronic renal allograft dysfunction: risk factors for graft loss and severe side effects

Daniel Abramowicz1, Karine Hadaya1, Marc Hazzan2, Nilufer Broeders1, Anh-Dung Hoang1, Lidia Ghisdal1, Christian Noel2 and Karl Martin Wissing1

1 Service de Néphrologie, Hopital Erasme, Bruxelles, Belgique 2 Service de Néphrologie, Hopital Calmette, Lille, France

Correspondence and offprint requests to: Daniel Abramowicz, Nephrology Department, Hopital Erasme, Université Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium. Tel: +32-2-555-33-34; Fax: +32-2-555-64-99; E-mail: dabram{at}ulb.ac.be



  Abstract

We retrospectively reviewed our experience with 45 kidney transplant recipients (KTR) that were switched from CNI to SRL, mainly for chronic allograft dysfunction (CAD) (41/45). The mean serum creatinine at switch was 2.5 ± 0.8 mg/dl. At 1 year, patient survival was 93%. Death-censored graft survival was 67% at 1 year and 54% at 2 years. SRL was stopped because of severe side effects in 15 patients. Among these, eight patients developed ‘de novo’ high-grade proteinuria. Univariate analysis revealed that (1) a higher SRL level at 1 month was a predictor of SRL withdrawal due to severe side effects (P = 0.006), and (2) predictors of graft failure after SRL conversion were low SRL loading dose (P = 0.03) and a higher creatinine level at conversion (P = 0.003).

In conclusion, the therapeutic index of SRL in patients suffering from CAD is narrow, with high exposure triggering serious adverse events that may mandate SRL discontinuation, while too low exposure may expose patients to under-immunosuppression and graft loss.

Keywords: graft survival; proteinuria; renal transplantation; sirolimus; toxicity

Received for publication: 30. 7.07
Accepted in revised form: 21. 5.08


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