The study assessed the removal of mycophenolic acid (MPA) and its major glucuronide metabolite (MPAG) during continuous venovenous hemofiltration (CVVHF) and continuous venovenous hemodiafiltration (CVVHDF) in 4 heart transplant recipients treated for at least 6 days with mycophenolate mofetil (MMF) in addition to cyclosporine and corticosteroids. The sieving coefficient ranged from 0.02 to 0.04 for MPA and from 0.15 to 0.33 for MPAG. The clearance of MPAG by CVVHDF or CVVHF ranged from 7.52 mL/min to 19.45 mL/min, and that of MPA was lower than 2.28 mL/min, with no significant difference between the two continuous replacement therapies. Whereas MPA percentage recovered by hour following CVVHDF or CVVHF was negligible, the percentage of MPAG represents up to 12.9% of the administered dose. A relevant decrease in the free fraction of MPA and MPAG was observed after continuous renal replacement therapy (CRRT). These preliminary results demonstrate that MPAG is able to permeate the filter. In light of the alteration in protein binding following CRRT and the competition between MPA and MPAG to albumin site, drug monitoring of MPA and MPAG in patients undergoing CVVHDF or CVVHF may be suggested. Moreover, monitoring of free MPA may be of interest for these patients.
a second-generation electrochemiluminescence PTH assay on the Elecsys 2010 platform (Roche Diagnostics). Ionized calcium and 25-hydroxyvitamin D (Nichols Advantage) were also measured in all samples.Results for the healthy individuals are presented in Fig. 1. The bio-intact PTH values measured by the IRMA and chemiluminescence immunoassay were, on average, 50% and 30% lower, respectively, than the PTH measured by the Elecsys. Regression analysis demonstrated significantly different slopes (P Ͻ0.001), but not intercepts, for both the IRMA and chemiluminescence immunoassay compared with the Elecsys assay. Most striking was the discordance between the ELISA and the IRMA, the chemiluminescence immunoassay, and the Elecsys assay. Comparison between the ELISA and Elecsys revealed a significantly different intercept (P Ͻ0.001). The results obtained with the third-generation IRMA and the chemiluminescence immunoassay also differed, despite the good correlation, and regression analysis demonstrated a significant difference for the slope (P Ͻ0.001) but not for the intercept. The finding of higher results with the chemiluminescence immunoassay concurs with the results reported by Boudou et al. (3 ), but immunoreactivity does not seem to be implicated in these differences (1-3 ). In addition to the apparent differences in assay design, other possible reasons for the lack of agreement between the assays investigated could be matrix effects and/or differences in standardization. The problems hampering immunoassay standardization are many and vary for different analytes, as has been reviewed by Stenman (4 ). Thus, the use of independent reference intervals for each of the bio-intact PTH assays is clinically important.We observed no significant differences between healthy individuals and patients with predialysis chronic kidney disease for 25-hydroxyvitamin D, but mean concentrations of bio-intact PTH (by chemiluminescence immunoassay; P Ͻ0.001) and ionized calcium (P Ͻ0.05) were higher in the patients. PTH measured by Elecsys was, on average, 75% higher than the measured biointact PTH in patients, consistent with the expected presence of high concentrations of circulating PTH fragments in patients with impaired renal function. In addition, the distribution of bio-intact PTH analyzed by the chemiluminescence immunoassay (mean, 71 ng/L; range, 5-227 ng/L) was wider in the patient group than in the healthy individuals [23 (11-50) Despite our strict adherence to the ELISA protocol and 3 independent runs with the same set of samples, this assay generated inconsistent results, which require additional methodologic studies to fully explain. We conclude that although the thirdgeneration bio-intact PTH ELISA requires further evaluation, the chemiluminescence immunoassay and IRMA are comparable.
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