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Late conversion from calcineurin inhibitor-based to sirolimus-based immunosuppression due to chronic toxicity: a prospective study with protocol biopsy amendment.
Uslu, A; Töz, H; Sen, S; Alkan, F T; Nart, A; Aykas, A; Dogan, M; Postaci, H; Sahin, T; Simsek, C.
Afiliação
  • Uslu A; T.C.S.B. Izmir Egitim ve Arastirma Hastanesi Organ Nakli Merkezi, Izmir/Turkey.
Transplant Proc ; 41(2): 756-63, 2009 Mar.
Article em En | MEDLINE | ID: mdl-19328973
BACKGROUND: There is an emerging consensus on conversion from calcineurin inhibitor (CNI)-based regimens to proliferation signal inhibitor (PSI)-based protocols for the prevention of a progressive decline in graft function due to CNI toxicity. METHODS: Thirty-one primary renal transplant recipients within 17-48 years of age (mean, 32.2 +/- 1.6) were enrolled in this dual-center study. Eligible patients had a baseline (pre-engraftment) biopsy and completed at least 12 months of follow-up with deteriorating graft function indicative of chronic CNI toxicity with or without nonspecific interstitial fibrosis/tubular atrophy (IF/TA) on a biopsy specimen. A fast conversion protocol, being defined as a 50% initial reduction followed by complete withdrawal of CNI drug within 2 weeks of introducing rapamycin was performed in all patients. A sirolimus (SRL) loading dose was not prescribed; all subjects directly received maintenance (2-5 mg/d) doses of the drug. The primary endpoint of this study was assessement of renal function using cGFR and renal histology by protocol biopsy at 1 year after conversion. RESULTS: The mean follow-up after conversion was 21.6 months. The difference between cGFR before compared with cGFR after 12 months after conversion (40.8 +/- 2.36 mL/min vs 55.7 +/- 3.6 mL/min; P < .000) and at the last follow-up (40.8 +/- 2.36 mL/min vs 53.8 +/- 2.96 mL/min; P < .000) was significant. The mean IF/TA with glomerulosclerosis and chronic vasculopathy scores of biopsy specimens at baseline, during conversion, and at 12 months of the study were 2.25 +/- 0.3, 3.30 +/- 0.24, and 3.0 +/- 0.30, respectively. The change in scores was indicative of mild progression; however, the difference was not significant. IF/TA, glomerulosclerosis, and chronic vasculopathy scores improved in 8 (30%) subjects, remained unchanged in 11 (42%) and worsened in 7 (28%) after 1 year of SRL therapy. After conversion there was no patient or graft loss in this group. Moreover, SCr and GFR improved in 21 or 29 patients (72%), remained stable in 4 (14%), and decreased in 4 (14%) patients. The predictors of successful conversion in our study were GFR > or = 40.6 mL/min, SCr < or = 2.34 mg/dL, and histological allograft damage score < or =3. CONCLUSION: SRL-MPA/MMF-ST combination may be a good therapeutic strategy against chronic CNI toxicity, particularly for patients whose conversion biopsy specimens demonstrated mild IF/TA, glomerulosclerosis, and chronic vasculopathy scores (< or =3.1 +/- 0.3).
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transplante de Rim / Calcineurina / Sirolimo / Imunossupressores Tipo de estudo: Guideline / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Humans / Middle aged Idioma: En Ano de publicação: 2009 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transplante de Rim / Calcineurina / Sirolimo / Imunossupressores Tipo de estudo: Guideline / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Humans / Middle aged Idioma: En Ano de publicação: 2009 Tipo de documento: Article