Adherence to lumacaftor-ivacaftor therapy in patients with cystic fibrosis in France.

BACKGROUND: Lumacaftor-ivacaftor combination is a promising treatment for cystic fibrosis (CF) patients homozygous for the F508del-CFTR mutation. Optimal adherence is essential to achieve full health outcomes benefits. METHODS: This retrospective study used pharmacy refills data to calculate proportion of days covered (PDC). Adherence was defined as a PDC ≥80%. A logistic regression analysis was conducted to examine factors associated with medication adherence. RESULTS: Ninety-six patients were included in the final cohort for analysis. The mean PDC was 96%  ± 14 at 6 months, and 91% ± 17 at 12 months. The proportion of adherent patients was 89% and 83% at 6 and 12 months respectively. Age and ppFEV1 were found to affect medication adherence. CONCLUSIONS: Considering the medico-economic impact of CFTR modulator therapy, high adherence rates to lumacaftor-ivacaftor found in this study are encouraging.

Comparison of ultrasound shear wave elastography with magnetic resonance elastography and renal microvascular flow in the assessment of chronic renal allograft dysfunction.

Background Monitoring of renal allograft function is essential for early identification of dysfunction and improvement of kidney transplant (KTX) outcome. Purpose To non-invasively assess renal stiffness in KTX recipients using ultrasound shear wave elastography (USE) in correlation with multifrequency magnetic resonance elastography (MRE), renal allograft function, and renal microvascular flow determined using a novel ultrasound microvascular imaging technique. Material and Methods This prospective study investigated 25 KTXs (functional KTX [FCT], n = 14; chronic KTX insufficiency [DYS], n = 11) in 20 KTX recipients (mean age = 43 ± 14 years). USE was performed using a high-frequency broadband linear transducer and compared with MRE. Shear wave velocity (SWV) was correlated with the estimated glomerular filtration rate (eGFR). Qualitative differences in renal microvascular flow were obtained using SMI. Results FCT had higher SWV than DYS in both cortex and pyramids (cortex, FCT: 3.75 ± 0.82 m/s vs. DYS: 2.79 ± 0.73 m/s, P = 0.0002; pyramid, FCT: 2.89 ± 0.46 m/s vs. DYS: 2.39 ± 0.34 m/s, P = 0.044). Cutoff values of 3.265 m/s for cortex, 2.535 m/s for pyramids, and 2.985 m/s for combined non-hilar parenchyma provided sensitivities of 72.7%, 77.8%, and 90.9% and specificities of 71.4%, 78.6%, and 85.7% for detecting renal allograft dysfunction with area under the receiver operating characteristic curve (AUC) values of 0.831, 0.841, 0.925 (95% confidence interval [CI] = 0.67-0.99, 0.66-1.02, 0.83-1.03). USE correlated positively with eGFR ( r = 0.741, P = 0.0004) and with MRE-derived SWV ( r = 0.562, P = 0.004). Renal microvascular flow was decreased in DYS. Conclusion USE is sensitive to renal allograft dysfunction, which is characterized by reduced SWV and renal perfusion. USE has higher image resolution than MRE, while MRE has slightly better diagnostic accuracy.

Multifrequency Magnetic Resonance Elastography for the Assessment of Renal Allograft Function.

OBJECTIVE: The aim of this study was to apply multifrequency magnetic resonance elastography (MMRE) for assessment of kidney function based on renal stiffness of allografts in transplant recipients and native kidneys in controls. METHODS: In this prospective study, MMRE was used to measure stiffness in transplant kidneys in 22 recipients (age range, 23-73 years; 7 females) and in native kidneys in 11 controls (age range, 26-55 years; 4 females) after internal review board approval. The MMRE was performed on a 1.5 T magnetic resonance imaging scanner using 4 vibration frequencies from 40 to 70 Hz. Stiffness maps were computed by multifrequency reconstruction of the magnitude shear modulus (|G*|). Clinical markers such as glomerular filtration rate (GFR) and resistive index (RI) were acquired. Differences in renal stiffness among groups were compared by Mann-Whitney U test. Correlations were tested using Pearson correlation. RESULTS: Functioning transplants had higher stiffness (|G*| = 9.00 ± 1.71 kPa) than nonfunctioning transplants (|G*| = 5.88 ± 1.71 kPa, P < 0.001) and native kidneys (|G*| = 6.63 ± 1.63 kPa, P < 0.01). A cutoff value of 7.04 kPa provided sensitivity (83.33%) and specificity (86.67%) for detecting renal allograft dysfunction with an area under the receiver operating characteristic curve value of 0.9278 (95% confidence interval, 0.83-1.00). |G*| correlated positively with GFR (r = 0.52, P = 0.015) and negatively with RI (r = -0.52, P = 0.016). CONCLUSIONS: Multifrequency magnetic resonance elastography has good diagnostic accuracy in detecting renal allograft dysfunction. Renal stiffness is significantly lower in recipients with nonfunctioning transplant kidneys and correlates with clinical markers such as GFR and RI.