The Relationship between Low Levels of Urinary Albumin Excretion and Microvascular Function
Thesis or dissertation
University of Exeter
Increased urinary albumin excretion, known as microalbuminuria, is an established clinical risk factor for renal disease in patients with diabetes. There is growing evidence that increasing urinary albumin even within the normal range, is a risk factor for cardiovascular disease (CVD) in subjects with and without diabetes. Microvascular dysfunction has been proposed as the common process in the pathophysiology of both diabetic renal disease and cardiovascular disease, resulting in increased urinary albumin excretion. This is further supported by evidence that urinary albumin excretion is associated with other microvascular complications of diabetes, such as retinopathy and neuropathy. It is important to investigate these relationships further as it could improve our ability to identify those at risk of CVD, and complications of diabetes at an earlier stage. This would result in significant improvement in the quality of lives of patients with diabetes and save the health service resources in managing the complications of diabetes. Studies that have investigated the relationship between albumin excretion and microvascular dysfunction are limited by the use of clinical assays, which cannot quantify low concentrations of urinary albumin. In this thesis an assay is validated to quantify low concentrations of urinary albumin. An accurate and reproducible method is developed to investigate low levels of urinary albumin excretion. This method was developed through two clinical studies and several laboratory experiments that investigated; a) the optimal method of collecting urine samples and reporting the results, b) the influence of exercise on urinary albumin excretion and c) the stability of urinary albumin in stored samples. Patients were selected from a prospective clinical study (SUMMIT) to investigate the relationship between low levels of urinary albumin excretion and in-vivo measures of microvascular function and microvascular complications of diabetes for the first time. This is 3 the first longitudinal study to report the change in these measures of microvascular function over three years and the influence of diabetes and CVD. This thesis provides novel evidence that increasing urinary albumin excretion, including within the normal range, is linked to generalised microvascular dysfunction. Furthermore, impaired microvascular autoregulation may play a role in the pathogenesis and is not influenced by diabetes. This is also supported by the association of urinary albumin excretion with background (early) changes in diabetic retinopathy.
PhD in Medical Studies