Nephrotic state substantially enhances apparent mycophenolic acid clearance
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BACKGROUND: Several factors may decrease plasma protein binding of mycophenolic acid (MPA), the active compound of mycophenolate mofetil (MMF), and potentially enhance its clearance. It is unclear if MMF dose adjustments are required for the treatment of steroid-resistant nephrotic syndrome (SRNS). Therapeutic drug monitoring of MPA levels is not widely utilized in the treatment of steroid-resistant nephrotic syndrome (SRNS). MATERIALS AND METHODS: In this retrospective cohort study, the authors measured 182 MPA predose trough levels (1 - 45/patient, HPLC/MS/MS) in 10 patients aged 0.9 - 18 years with SRNS treated with MMF. Apparent MPA clearances (CL/F) were calculated from the dose/estimated AUC. Anthropomorphic data, blood parameters, and proteinuria levels were collected from electronic health records. We compared all parameters with apparent MPA clearance, including albumin level, microalbuminuria, proteinuria, triglycerides, cystatin C, and estimated glomerular filtration rate (eGFR), analyzed by nonlinear regression analysis. RESULTS: Median apparent clearance was 22.63 L/h (IQR 17.1, 32.47). Significant correlations were found between MPA Cl/F and serum albumin (r = -0.47), microalbuminuria (+0.54), triglycerides (+0.33), and cholesterol (+0.32). CL/F increased from a minimum of 2.4 L/h for the highest albumin levels to a maximum of 59.9 for albumin levels \u3c 25 g/L. Similarly, the apparent MPA clearance increased significantly with higher triglycerides and lower hematocrit. CONCLUSION: This study confirms a significant increase of the apparent clearance of MPA with low serum albumin, microalbuminuria, proteinuria, high triglycerides, and low hematocrit. The 20-fold increase of the apparent clearance suggests that MMF unresponsiveness in the nephrotic state may be related to MPA underexposure.