Exploring genetic and non-genetic risk factors for delayed graft function, acute and subclinical rejection in renal transplant recipients.
Br J Clin Pharmacol
; 82(1): 227-37, 2016 07.
Article
en En
| MEDLINE
| ID: mdl-27334415
ABSTRACT
AIMS:
This study aimed at identifying pharmacological factors such as pharmacogenetics and drug exposure as new predictive biomarkers for delayed graft function (DGF), acute rejection (AR) and/or subclinical rejection (SCR).METHODS:
Adult renal transplant recipients (n = 361) on cyclosporine-based immunosuppression were followed for the first 6 months after transplantation. The incidence of DGF and AR were documented as well as the prevalence of SCR at 6 months in surveillance biopsies. Demographic, transplant-related factors, pharmacological and pharmacogenetic factors (ABCB1, CYP3A5, CYP3A4, CYP2C8, NR1I2, PPP3CA and PPP3CB) were analysed in a combined approach in relation to the occurrence of DGF, AR and prevalence of SCR at month 6 using a proportional odds model and time to event model.RESULTS:
Fourteen per cent of the patients experienced at least one clinical rejection episode and only DGF showed a significant effect on the time to AR. The incidence of DGF correlated with a deceased donor kidney transplant (27% vs. 0.6% of living donors). Pharmacogenetic factors were not associated with risk for DGF, AR or SCR. A deceased donor kidney and acute rejection history were the most important determinants for SCR, resulting in a 52% risk of SCR at 6 months (vs. 11% average). In a sub-analysis of the patients with AR, those treated with rejection treatment including ATG, significantly less frequent SCR was found in the 6-month biopsy (13% vs. 50%).CONCLUSIONS:
Transplant-related factors remain the most important determinants of DGF, AR and SCR. Furthermore, rejection treatment with depleting antibodies effectively prevented SCR in 6-month surveillance biopsies.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Farmacogenética
/
Trasplante de Riñón
/
Funcionamiento Retardado del Injerto
/
Rechazo de Injerto
Tipo de estudio:
Clinical_trials
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Br J Clin Pharmacol
Año:
2016
Tipo del documento:
Article
País de afiliación:
Países Bajos