Determinants of Successful Use of Sirolimus in Renal Transplant Patients.
Journal
Transplantation proceedings
ISSN: 1873-2623
Titre abrégé: Transplant Proc
Pays: United States
ID NLM: 0243532
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
30
01
2020
accepted:
13
02
2020
pubmed:
5
6
2020
medline:
16
2
2021
entrez:
5
6
2020
Statut:
ppublish
Résumé
Sirolimus is an established immunosuppressant in renal transplantation with antineoplastic and antiviral features, but side effects like proteinuria limit its use. The aim of this retrospective multicenter observational study is to define predictors for determining which patients most likely benefit from a sirolimus-based therapy. All patients from 10 German centers that were switched to a sirolimus-containing maintenance immunosuppression in 2000 to 2008 after 3 months or later post-transplantation were enrolled (n = 726). Observation times after switching to sirolimus ranged from 4 days to 9 years (median: 24.3 months). With multinomial logistic regression, risk factors for the endpoints terminal graft failure and withdrawal of sirolimus therapy compared to successful therapy were identified. Successful sirolimus therapy was observed in 304 patients. Forty patients died with functioning graft. Therapy failures included graft loss (n = 106) and sirolimus-discontinuation for various reasons (n = 276). Successful sirolimus-use was predicted in 83% and graft failure in 65%, whereas prediction of deliberate sirolimus-discontinuation was poor (48%). Most favorable results for sirolimus-use were observed in patients switched in 2006 to 2008. Using ROC analysis, an estimated glomerular filtration rate (eGFR) below 32 mL/min was shown to be the cut-off in patients withdrawing from therapy as a result of renal reasons, as well as in patients with graft loss. Proteinuria above 151 mg/L was shown to be predictive for patients with graft failure. eGFR and proteinuria are the major determinants for successful sirolimus-therapy. Our findings help stratifying patients who will benefit most from this therapy and avoid toxicities in patients without potential benefits for this therapy.
Sections du résumé
BACKGROUND
BACKGROUND
Sirolimus is an established immunosuppressant in renal transplantation with antineoplastic and antiviral features, but side effects like proteinuria limit its use. The aim of this retrospective multicenter observational study is to define predictors for determining which patients most likely benefit from a sirolimus-based therapy.
METHODS
METHODS
All patients from 10 German centers that were switched to a sirolimus-containing maintenance immunosuppression in 2000 to 2008 after 3 months or later post-transplantation were enrolled (n = 726). Observation times after switching to sirolimus ranged from 4 days to 9 years (median: 24.3 months). With multinomial logistic regression, risk factors for the endpoints terminal graft failure and withdrawal of sirolimus therapy compared to successful therapy were identified.
RESULTS
RESULTS
Successful sirolimus therapy was observed in 304 patients. Forty patients died with functioning graft. Therapy failures included graft loss (n = 106) and sirolimus-discontinuation for various reasons (n = 276). Successful sirolimus-use was predicted in 83% and graft failure in 65%, whereas prediction of deliberate sirolimus-discontinuation was poor (48%). Most favorable results for sirolimus-use were observed in patients switched in 2006 to 2008. Using ROC analysis, an estimated glomerular filtration rate (eGFR) below 32 mL/min was shown to be the cut-off in patients withdrawing from therapy as a result of renal reasons, as well as in patients with graft loss. Proteinuria above 151 mg/L was shown to be predictive for patients with graft failure.
CONCLUSIONS
CONCLUSIONS
eGFR and proteinuria are the major determinants for successful sirolimus-therapy. Our findings help stratifying patients who will benefit most from this therapy and avoid toxicities in patients without potential benefits for this therapy.
Identifiants
pubmed: 32493677
pii: S0041-1345(19)31510-6
doi: 10.1016/j.transproceed.2020.02.159
pii:
doi:
Substances chimiques
Immunosuppressive Agents
0
Sirolimus
W36ZG6FT64
Types de publication
Journal Article
Multicenter Study
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
3103-3111Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.