The Relationship Between Weight Indices and Blood Levels of Immunosuppressive Drugs in Renal Transplant Recipients

Abstract

Background: Calcineurin inhibitors and mammalian target of rapamycin (mTOR) inhibitors are essential for maintainingtransplanted organs. However, determining the appropriate dosage and predicting blood concentrations of these drugs basedsolely on net body weight may be inadequate. Previous studies have presented contradictory results regarding the impact ofobesity on drug concentrations and transplant success. Objectives: This study aims to evaluate various weight indices to identify the most reliable indicator of weight that correlateswith the blood levels of drugs used in organ transplantation. Methods: This retrospective descriptive study included patients from nephrology clinics affiliated with Isfahan University ofMedical Sciences who were taking calcineurin and/or mTOR inhibitor drugs. Data extracted from medical records includeddemographic and clinical information, such as height, weight, and various weight indices (total/ideal/adjusted body weight,lean body mass (LBM), Body Mass Index, and predicted normal weight), as well as blood levels of immunosuppressive drugs ateach patient's visit. The dosages of each drug (mg/kg) were analyzed to determine which weight indices best correlated with theobtained blood concentrations, using the Generalized Estimating Equation (GEE) model with logistic regression, anindependent correlation matrix, and a binary distribution for data analysis. Results: The study analyzed the medical records of 71 patients. Trough (C0) concentrations of drugs were evaluated in relationto each weight index, and odds ratios (OR) were calculated for statistical comparison. All weight indices increased the likelihoodof achieving appropriate concentrations for cyclosporine, tacrolimus, and sirolimus. Drug dosing based on LBM (OR: 1.028),ideal body weight (OR: 1.075), and total body weight (OR: 1.041) showed the strongest correlations with achieving proper bloodlevels for cyclosporine, tacrolimus, and sirolimus, respectively. Conclusions: Integrating various weight indices for calculating individualized doses (mg/kg) of each immunosuppressive drugincreases the likelihood of achieving appropriate blood concentrations. However, the optimal weight index varies for each drug.Further studies, particularly those incorporating therapeutic drug monitoring (TDM) plans in transplant centers, are warrantedto validate and generalize these findings, providing a potential avenue for improving immunosuppressive therapy andenhancing transplant outcomes.