PRIM-TxAIR Precision Response Individualized Monitoring of Exhaled Biomarkers After Kidney Transplantation

The concept of personalized medicine revolves around providing the right treatment for the right person at the right time. This is especially critical for immunosuppressants used in kidney transplantation, such as Tacrolimus, Cyclosporine A, and Mycophenolate Mofetil. These drugs possess a narrow therapeutic window where the gap between efficacy and toxicity is minimal. High inter-individual variability necessitates rigorous Therapeutic Drug Monitoring (TDM) to avoid graft rejection or drug-induced nephrotoxicity.

While TDM is a clinical standard, its reliance on frequent venipuncture remains highly invasive. This is particularly significant for pediatric patients, who suffer from needle-related trauma and reduced treatment adherence. Scientific evidence indicates that up to 80 percent of adolescent transplant recipients experience non-adherence, which serves as a primary driver of preventable graft rejection and late allograft loss. Adherence is the most important modifiable factor that affects treatment outcomes [8]. This challenge in compliance is closely linked to the physical and psychological burden of current monitoring practices: frequent, invasive venipuncture often results in procedural distress and 'medical fatigue' . There is a clear and compelling clinical need for non-invasive alternatives to alleviate this burden and safeguard long term graft survival.

The PRIM-TxAIR project builds upon our lab's successful preliminary work in TDM of epilepsy. In our previous study, our lab demonstrated that Secondary Electrospray Ionization High Resolution Mass Spectrometry (SESI-HRMS) can accurately track multi-drug regimens in real time within the exhaled breath of pediatric epilepsy patients. We established that circulating drugs diffuse across the air-blood barrier in the lungs, making breath a viable surrogate for systemic concentrations. This project translates that technology to transplantation.

The objective is to provide a non-invasive, patient-specific solution for transplant recipients. Cutting-edge mass spectrometry will be combined with sophisticated Regression models to predict blood concentrations from breath read-outs. By integrating metabolic phenotyping, we aim to identify signs of rejection or toxicity before they manifest clinically. This transition from invasive blood draws to painless breath analysis aims to reduce the frequency of venipuncture by 50%. The project will run from April 2026 to March 2027 for clinical implementation (part of this grant application), followed by an intensive data analysis phase from April 2027 to October 2028 (outside grant application).