Metabolic profiling in chronic venous ulceration

Abstract

Introduction: This thesis seeks to determine the potential utility of metabolic profiling in chronic venous ulceration of the lower limb. Venous ulceration is a final common pathway for legs subjected to abnormally sustained and elevated venous pressures either as a consequence of venous obstruction or reflux. What is not clear is how venous abnormalities contribute to the syndrome of tissue loss. This thesis has outlined the present understanding of the pathogenesis of venous ulceration and has sought to outline the role of hypothesis generating metabolic profiling that may be able to shed new light on venous leg ulceration. Methods: After a pilot study and concurrent development of methods. A cohort of patients with venous ulceration was recruited with the appropriate ethical approval for sequential clinical assessments and sampling of urine, serum and ulcer fluid (captured by sterile filter paper discs). Global metabolic profiling using nuclear magnetic resonance and mass spectrometry was performed and multivariate statistical analysis was performed according to known clinical variables that have been able to predict ulcer healing in the literature. Results: Multivariate statistical analysis revealed that it was possible to discriminate between clinical prognostic groups based on the global metabolic profile of urine, serum and ulcer fluid. Multiple potential metabolite markers were identified and will be studied in detail in future work in terms of relevance to the pathogenesis of chronic venous ulceration and to prediction of prognosis. Conclusion: This novel work has demonstrated the utility of metabolic profiling in chronic venous ulceration of the lower limb. When stratified for clinical parameters related to prognosis or ulcer healing status a variable metabolic phenotype was identified. Future work will involve the detailed characterisation of the metabolite features responsible for difference between clinical groups, validate the results of this thesis in a larger cohort as a prognostic tool and consider the role of venous ulcer biopsy.