The role of novel biomarkers in addressing the burden of chronic kidney disease in diabetes mellitus
Griffin, Tomás Patrick
Griffin, Tomás Patrick
Loading...
Publication Date
2022-10-06
Type
Thesis
Downloads
Citation
Abstract
Kidney disease due to diabetes (Diabetic Kidney Disease (DKD)) is the leading cause of chronic kidney disease worldwide. It is an underappreciated, often under-recognised component of the overall burden of diabetes. People with diabetes and kidney disease are at increased risk of all cause and cardiovascular mortality compared with those with diabetes (and no kidney disease), kidney disease (and no diabetes) and those without kidney disease or diabetes. There is an unmet clinical need for biomarkers to allow the early identification of those at risk of developing DKD. Early identification would allow for earlier intensive targeted interventions. My thesis aims to assess the prevalence of and factors associated with DKD and rapid decline in renal function among people with diabetes, explore the association between potential novel biomarkers and the onset and progression of DKD and establish reference intervals (RIs) for novel and routinely used biomarkers. Firstly, I determined the prevalence of DKD and rapid renal function decline among adults attending a Diabetes Centre in Northern Europe. I identified clinical and laboratory indices that were associated with rate of decline in renal function. Secondly, I developed a clinical database linked to a collection of serum, plasma, urine (centrifuged and uncentrifuged) and peripheral blood mononuclear cells (PBMC) to explore the role of novel biomarkers in predicting decline in renal function in people with diabetes [The BioDIG (Biomarkers in Diabetes in Galway) study]. From this database, I examined the utility of plasma dephosphorylated-uncarboxylated matrix gla-protein (dp-ucMGP) to distinguish people with DKD from those with diabetes and no DKD and healthy volunteers. I explored the ability of dp-ucMGP to identify people with diabetes at risk of rapid decline in renal function. I examined the role of serum growth differentiation factor-15 (GDF-15) in distinguishing people with DKD from those without. In collaboration with colleagues in the Mayo Clinic, Rochester, USA, I examined the relationship between DKD and various relevant renal indices and increased production of the senescence-associated protein Activin A in people from the BioDIG study and people recruited in the Mayo Clinic. Next and for the first time in a human study, I determined the impact of sodium glucose co-transporter-2 (SGLT-2) inhibition on aldosterone, renin and the aldosterone renin ratio in people with type 2 diabetes. Finally, I established RIs for widely used biochemical and haematological parameters and novel biomarkers such as dp-ucMGP and GDF-15 in a healthy Irish Adult Caucasian population. The published work described in this thesis provides important new information from a public health perspective on the prevalence of DKD and rapid decline in renal function among people in Ireland with type 1, type 2 and other forms of diabetes. Furthermore, in a carefully curated cohort of adults with diabetes and healthy volunteers, the potential of several novel biomarkers has been demonstrated. Follow-up of the BioDIG cohort is ongoing and is likely to provide more novel insights into the utility of the biomarkers described and others as the duration of follow-up increases.
Publisher
NUI Galway