Estimation of Mycophenolic Acid Exposure in Chinese Renal Transplant Patients by a Joint Deep Learning Model

摘要

Background:To predict mycophenolic acid (MPA) exposure in renal transplant recipients using a deep learning model based on a convolutional neural network with bilateral long short-term memory and attention methods.Methods:A total of 172 Chinese renal transplant patients were enrolled in this study. The patients were divided into a training group (n = 138, Ruijin Hospital) and a validation group (n = 34, Zhongshan Hospital). Fourteen days after renal transplantation, rich blood samples were collected 0-12 hours after MPA administration. The plasma concentration of total MPA was measured using an enzyme-multiplied immunoassay technique. A limited sampling strategy based on a convolutional neural network-long short-term memory with attention (CALS) model for the prediction of the area under the concentration curve (AUC) of MPA was established. The established model was verified using the data from the validation group. The model performance was compared with that obtained from multiple linear regression (MLR) and maximum a posteriori (MAP) methods.Results:The MPA AUC(0-12) of the training and validation groups was 54.28 +/- 18.42 and 41.25 +/- 14.53 mu g center dot ml(-1)center dot h, respectively. MPA plasma concentration after 2 (C-2), 6 (C-6), and 8 (C-8) hours of administration was the most significant factor for MPA AUC(0-12). The predictive performance of AUC(0-12) estimated using the CALS model of the validation group was better than the MLR and MAP methods in previous studies (r(2) = 0.71, mean prediction error = 4.79, and mean absolute prediction error = 14.60).Conclusions:The CALS model established in this study was reliable for predicting MPA AUC(0-12) in Chinese renal transplant patients administered mycophenolate mofetil and enteric-coated mycophenolic acid sodium and may have good generalization ability for application in other data sets.