Determination of mycophenolic acid in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry and its pharmacokinetic application in kidney transplant patients.

To implement and validate an analytical method by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC MS/MS) to quantify mycophenolic acid (MPA) in kidney transplant patients. Quantification of MPA was performed in an ACQUITY UPLC H Class system coupled to a Xevo TQD detector and it was extracted from plasma samples by protein precipitation. The chromatographic separation was achieved through an ACQUITY HSS C18 SB column with 0.1% formic acid and acetonitrile (60:40 vol/vol) as mobile phase. The pharmacokinetic parameters were calculated by non-compartmental analysis of MPA plasma concentrations from 10 kidney transplant patients. The linear range for MPA quantification was 0.2-30 mg/L with a limit of detection of 0.07 mg/L; the mean extraction recovery was 99.99%. The mean intra- and inter-day variability were 2.98% and 3.4% with a percentage of deviation of 8.4% and 6.6%, respectively. Mean maximal concentration of 10 mg/L at 1.5 h, area under the concentration-time curve of 36.8 mg·h/L, elimination half-life of 3.9 h, clearance of 0.32 L/h/kg and volume of distribution of 1.65 L/kg were obtained from MPA pharmacokinetics profiles. A simple, fast and reliable UPLC-MS/MS method to quantify MPA in plasma was validated and has been applied for pharmacokinetic analysis in kidney transplant patients.

Clinical and Echocardiographic Factors Associated with Right Ventricular Systolic Dysfunction in Hemodialysis Patients.

BACKGROUND: Chronic kidney disease is a disorder of epidemic proportions that impairs cardiac function. Cardiovascular diseases are the leading cause of death in hemodialysis patients, and the understanding of new nontraditional predictors of mortality could improve their outcomes. Right ventricular systolic dysfunction (RVSD) has recently been recognized as a predictor of cardiovascular death in heart failure and hemodialysis patients. However, the factors contributing to RVSD in hemodialysis patients remain unknown. The aim of this study was to evaluate the clinical and echocardiographic factors associated with RVSD in hemodialysis patients. METHODS: A cross-sectional study was conducted in which 100 outpatients with end-stage renal disease on chronic hemodialysis were evaluated. A transthoracic echocardiographic examination was performed at optimal dry weight. Right ventricular systolic function was evaluated using tricuspid annular plane systolic excursion (TAPSE). Clinical and echocardiographic data were recorded for each patient. A multivariate linear logistic regression was created using RVSD (TAPSE <14 mm) as the dependent variable. RESULTS: Fifteen patients with RVSD and 85 patients without RVSD were analyzed. TAPSE had a positive correlation with left ventricular ejection fraction (LVEF) and myocardial relaxation velocity. Independent contributors to RVSD were LVEF (OR 1.14, 95% CI 1.05-1.26), left ventricular mass index (OR 1.02, 95% CI 1.00-1.04), and myocardial relaxation velocity (OR 1.81, 95% CI 1.18-3.19). CONCLUSIONS: Echocardiographic factors were significant contributors to RVSD. These measurements could be included as part of the routine workup in all end-stage renal disease patients on hemodialysis.