03, GraphPad Software, La Jolla, CA, USA) and SPSS (IBM SPSS Statistics for Windows, version 20.0.0.2, IBM Corporation, Armonk, NY, USA). A p-value of <0.05 was considered statistically significant. 2.4.1 Correlation Between Glomerular Filtration Rate (GFR) Equations and Dabigatran Concentrations The primary aim of the correlation analysis was to assess the correlations of the estimated GFR values with dabigatran concentrations normalised for all other known covariates. This analysis selleck chemicals llc was conducted

in two stages, as follows. 1. Dose-corrected trough plasma dabigatran concentrations (dabigatrantrough, with units of µg/L per mg/day) were regressed against non-renal clinical factors (covariates) known to alter dabigatran exposure (Table 1), as well as the time period between the last dose of dabigatran etexilate and the trough sample. Other than the time period, which was treated as a continuous variable, all of the non-renal covariates were treated as nominal variables. The dabigatrantrough values were log-transformed, and were tested for normality using the D’Agostino–Pearson omnibus test (with p > 0.05 indicating that the data IWR-1 mouse passed the normality test). If these data were judged to be normally distributed, the log-transformed dabigatrantrough values were then converted to z-scores (standardised values). Covariates were entered simultaneously into a multiple linear regression model based

on biological plausibility rather than statistical criteria. These covariates included those that have been found in the literature to significantly correlate with either dabigatran area under the concentration–time curve (AUC) or trough plasma concentrations. Using this model, standardised residuals were generated

for each individual.   2. The estimates of GFR (in units of mL/min) from each of the four equations were standardised (z-scores) and then correlated (R 2), in turn, with the HSP90 standardised residuals from the regression model described above. The R 2 values from each of the four renal function equations were compared on the basis of the 95 % CI of each R 2 value. Further, the unstandardised residuals, from the correlation between each renal function equation and the standardised residuals of the multiple linear regression model, were compared using repeated measures one-way analysis of variance (ANOVA). Finally, the equation with the highest R 2 was included in the multiple linear regression model, and the R 2 of this model for the z-scores of the log-transformed dabigatrantrough calculated.   These TAM Receptor inhibitor analyses were repeated after excluding patients on corticosteroids and/or with abnormal thyroid function tests. Corticosteroid therapy and abnormal thyroid function tests have been demonstrated to substantially affect plasma cystatin C concentrations [46], and therefore would be expected to impact on cystatin C-based renal function equations.