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

Research Project | 2 Project Members

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).

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Individualized Drug Dosage Guided by Breath Analysis

Research Project | 3 Project Members

For a small fraction of all therapeutic drugs currently used, routine monitoring is crucial. The reason for this is that the gap between therapeutic and toxic concentration is very narrow. This, combined with the fact that there exists high inter-individual variability, has led to the need for therapeutic drug monitoring (TDM). The goal of TDM is to individualize the dosage to achieve maximum efficacy and at the same time minimize drug toxicity. TDM has obvious clinical benefits for patients and healthcare systems. However, TDM in children is particularly challenging. In addition, traditionally used venipunctures to determine drug concentrations are not well tolerated by children. The goal of this project is to address these challenges by providing a non-invasive and patient-specific solution, whereby drugs requiring TDM in children will be monitored in exhaled breath. We will use a cutting-edge analytical platform (i.e. secondary electrospray ionization-mass spectrometry) available at the University Children's Hospital Basel to detect drugs in breath with unparalleled speed, selectivity and sensitivity. Initially, we will measure simultaneously blood and breath concentrations of drugs routinely monitored in our hospital (e.g. anti-convulsants). We will then use this information as an input to develop pharmacokinetic computational models to predict blood concentrations based on the breath test read-out. During the final phase, we will validate these models in an independent group of patients to proof the clinical transferability of breath-based tests to guide drug dosage on an individual basis. This project will have a tremendous impact on current pediatric TDM clinical practice by: i) enabling a more personalized treatment, hence reducing ineffective doses and adverse effects; ii) improving patients' outcome; iii) saving hospital costs and iv) gaining new insights on pharmacokinetic aspects such as key parameters governing the diffusion of drugs in the lungs.