Project Details
Projekt
SP1: Evaluating Pharmacokinetic/Pharmacodynamic and innate immune parameters in the pyelonephritis environment
Subject Area
Reproductive Medicine, Urology
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 466687329
Pyelonephritis is frequent and causes substantial morbidity. Uropathogens causing pyelonephritis become increasingly antibiotic-resistant, hindering successful treatment. Patients suffering from pyelonephritis are clinically very heterogeneous and the parameters which decide treatment success or failure are not comprehensively understood. This project aims to elucidate the changes in blood and urine in human pyelonephritis and the effect of innate immune parameters on anti-infective treatment. This project transfers knowledge from deeply phenotyped pyelonephritis patients into pharmacological models, pursuing specific clinical and experimental aims. The alteration of blood and urine of pyelonephritis and control groups will be characterized by analyzing the physico-chemical properties, the proteome with a focus on antimicrobial peptides, and the number and differentiation status of myeloid cells. Alterations will be analyzed bioinformatically and correlated with the severity and clinical course of pyelonephritis. Nonclinical, ex vivo pharmacological models for investigation of antibiotics, namely pharmacokinetic and pharmacodynamic assessments, will be adapted to the peculiar pyelonephritis environment, including antimicrobial peptides. Selected myeloid cells will be incorporated into the pharmacological study by using the hollow-fiber model to investigate the additional anti-infective effect of immune cells in pharmacokinetic and pharmacodynamic models. The goal of this proposal is to better understand the molecular and cellular changes in blood and urine during pyelonephritis and its effect on anti-infective treatment. This will optimize available treatment strategies and delineate novel strategies for pyelonephritis therapy.
DFG Programme
Research Units
