Validation of the psychometrics properties of a French quality of life questionnaire among a cohort of renal transplant recipients less than one year.

BACKGROUND: Renal transplantation is considered as the treatment of choice for patients with end-stage renal disease. Health-related quality of life (HRQoL) of renal transplant recipients (RTR) is very important to assess, especially during the first year after transplantation. To provide new evidence about the suitability of HRQoL measures in RTR during the first post-transplant year, we explored the internal structure, reliability and external validity of a French specific HRQoL instrument, the Renal Transplant Quality of life Questionnaire Second Version (RTQ V2). METHODS: The data were issued from the French multicenter cohort of renal transplant patients followed during 4 years (EPIGREN). The HRQoL of RTR was assessed five times (at 1, 3, 6, 9 and 12 months after transplantation) with the RTQ V2, a specific instrument consisting of 32 items describing five dimensions. Socio-demographic information, clinical characteristics and HRQoL (i.e., RTQ V2 and SF-36) were collected. For the five times, psychometric properties of the RTQ V2 were compared to those reported from the reference population assessed in the validation study. RESULTS: Three hundred and thirty-four patients were enrolled. The proportions of well-projected items, item-internal consistency, item-discriminant validity, floor and ceiling effects, Cronbach's alpha coefficients and item goodness-of-fit statistics were satisfactory for each dimension at the five times of the study. The suitability indices of construct validity were higher than 90 % for each time (minimum-maximum: 90.8-97.4 %). The external validity was less satisfactory, with a suitability indices ranged from 46.7 % at M1 to 66.7 % at M12. However, the discrepancies with the reference population (mainly for the gender) appeared logical considering the scientific literature on HRQoL of RTR during the first post-transplant year and may not compromise the external validity. CONCLUSION: These results support the validity and reliability of the RTQ V2 for evaluating HRQoL in RTR during the first post-transplant year, and confirm that the RTQ V2 is a useful tool to assess the HRQoL precociously after transplant.

Evolution and Determinants of Health-Related Quality-of-Life in Kidney Transplant Patients Over the First 3 Years After Transplantation.

BACKGROUND: Health-related quality of life (HRQOL) usually improved after kidney transplantation; however, a non-negligible number of patients did not benefit from transplantation in HRQOL. The aims of this cohort study were to describe the evolution of HRQOL in kidney transplant recipients to search for subgroups with distinct time profiles and to investigate these determinants. METHODS: Three hundred thirty-seven adult patients were followed up from 1 to 36 months after kidney transplantation. Each patient completed repeated HRQOL assessments (median, 5; range, 2-9). K-means for longitudinal data was used to identify homogeneous clusters of HRQOL time profiles obtained for the mental and physical composite scores (MCS and PCS) and for the 8 dimensions of the short-form 36 scale. Covariates associated with these clusters were investigated using random forest analysis. Magnitude and shape of the HRQOL variations over time were investigated using linear regression mixed models. RESULTS: Two longitudinal clusters were identified for the time profiles of PCS and MCS. Patients classified in the higher cluster (ie, 60% of the population) exhibited a steady-state HRQOL, similar on average to the general population, whereas in the lower cluster, PCS and MCS scores were significantly lower than in the general population. Muscular weakness in the first year after transplantation explained 19% of the interpatient variability of PCS 3 months after transplantation, whereas associated with anxiety, it explained 24% of interpatient MCS variability. CONCLUSIONS: This work suggests to promote (i) physical rehabilitation programs after transplantation to curb the muscular loss and (ii) systematic attention to the patient's anxiety.

Ciclosporin population pharmacokinetics and Bayesian estimation in thoracic transplant recipients.

BACKGROUND AND OBJECTIVES: Therapeutic drug monitoring of ciclosporin has been recognized as an essential tool in the management of allograft transplant recipients, as it could help improve their outcome. However, there is still no consensus about the optimal method for monitoring ciclosporin after thoracic transplantation. Better knowledge of the pharmacokinetics of ciclosporin in thoracic transplant patients and design of tools dedicated to ciclosporin monitoring could help its practice and its outcome in this population of patients. The aims of this study were to (i) investigate the population pharmacokinetics of ciclosporin in thoracic (heart or lung) transplant patients and study the influence of a range of potential covariates, including demographic, clinical and genetic factors, on pharmacokinetic parameters; and (ii) develop a Bayesian estimator able to predict the individual pharmacokinetic parameters and exposures indices in this population of patients. METHODS: The analysis was performed with 187 full pharmacokinetic profiles obtained in 57 lung and 19 heart transplant patients within the first year post-transplantation. A population pharmacokinetic model was developed by non-linear mixed-effects modelling using NONMEM(®) (version 7.1) from an index dataset (118 profiles). On the basis of this population model and a limited number of blood samples, a Bayesian estimator able to determine ciclosporin area under the blood concentration-time curve (AUC) during a dosage interval was built and evaluated in the validation dataset (69 profiles). RESULTS: Ciclosporin pharmacokinetics were described using a two-compartment model with time-lagged first order absorption and first-order elimination. The final population model included sex as a covariate: ciclosporin apparent oral clearance was on average 37 % faster in male than in female patients (34.8 vs. 25.4 L/h, p < 0.001). Good predictive performance of the Bayesian estimator was obtained using three blood concentrations measured at 40 min, 2 h and 4 h post-dose, with a non-significant bias of -5 % between the estimated and the reference trapezoidal AUC and a good precision (relative mean square error = 13 %). CONCLUSION: Ciclosporin population pharmacokinetic analysis in thoracic transplant patients (including patients with cystic fibrosis) showed a significant influence of sex on apparent clearance. The Bayesian estimator developed in this study yielded accurate prediction of ciclosporin exposure in this population throughout the first year post-transplantation. This tool may allow routine ciclosporin dose individualization.