This thesis describes the development and evaluation of a new laboratory tool to improve early kidney injury diagnosis. In the first part, we define the unmet clinical needs in the clinical care... Show moreThis thesis describes the development and evaluation of a new laboratory tool to improve early kidney injury diagnosis. In the first part, we define the unmet clinical needs in the clinical care pathways in kidney injury, by a questionnaire and s literature review to summarize current state-of-the-art diagnostics. The second part of this thesis comprises the analytical phase of test development. Liquid-chromatography (LC) coupled to tandem MS was chosen as analytical platform for protein-based kidney injury biomarker quantitation from human urine specimens. The third part of this thesis covers aspects of the postanalytical phase of medical test development, which included the establishment of reference intervals and clinical observational cohort studies. Elevated levels of the studied kidney injury biomarkers, and their combined signatures, were associated with acute kidney injury induced by ischemia-reperfusion injury after kidney transplantation, but not with stable chronic kidney disease. In a general perspective, this thesis highlights the role of quantitative protein mass spectrometry for biomarker translation from research towards the clinical laboratory. Show less
This thesis describes very sensitive methods for peptide detection, obtained by the coupling of high efficiency capillary chromatographic techniques to mass spectrometry. The application of novel... Show moreThis thesis describes very sensitive methods for peptide detection, obtained by the coupling of high efficiency capillary chromatographic techniques to mass spectrometry. The application of novel data preprocessing methods to the analysis of such complex MS data generated is also described. The data analysis step was completed by the use of multivariate statistical analysis tools, such as principal component analysis (PCA). The developed platform could be applied to the study of complex peptide mixtures and of proteomic samples. Show less
