JMIR Publications

ABSTRACT

We utilised a cross-sectional study of people with diabetes and chronic kidney disease (CKD) to identify potential biomarkers associated with progressive renal injury and to distinguish between stages of chronic kidney disease. Three sources of biomarkers were explored, namely, DNA methylation profiles in blood lymphocytes, metabolomic profile of blood-derived serum and urine, as well as the gut microbiome. The importance of identifying people with diabetes and progressive kidney dysfunction relates to the excess morbidity and mortality of this group. Indeed the rate of cardiovascular disease is much higher in people with both diabetes and kidney dysfunction than in those with either alone. A subset of individuals with diabetes will develop chronic kidney disease characterised by hypertension, persistent proteinuria, and progressive decline in kidney function. By the time these people are identified in current clinical practice proteinuria and renal dysfunction are already established, limiting the effectiveness of therapeutic interventions. The endothelial dysfunction and inflammatory milieu which underpin diabetes associated chronic kidney disease is established and cardiovascular risk conferred. In this research project, we aim to assess whether there is a relationship between stages of diabetic CKD and epigenetic profile, blood and urine metabolomic profiles and the faecal microbiome. The identification of an epigenetic or blood metabolite signature or gut microbiome profile may identify those with diabetes at risk of progressive chronic kidney disease. This in turn would provide targeted intervention to improve patient outcomes. There has been an upsurge in the understanding and knowledge of the epigenome, metabolomics and the gut microbiome and its influence on the incidence of many diseases, such as cancer, particularly in association with specific environmental exposures. However, there is a paucity of literature surrounding these influencers in renal disease. The current study will provide insight into the fundamental understanding on the pathophysiology of chronic kidney disease in individuals with diabetes, especially in relation to novel areas such as epigenetics, metabolomics and the kidney-gut axis.