DrDebra Higgins

Chronic Kidney Disease (CKD) affects approximately one in twenty five people in Ireland. There is no cure for CKD and current treatment therapies are aimed at slowing disease progression to end stage renal disease, which requires patients to undergo renal replacement therapy such as dialysis or kidney transplantation. Treating patients with kidney disease in Ireland consumes approximately 10% of the total Irish health care budget. Diabetes and hypertension are two major causes of CKD. Diabetes is a global health problem with approximately 250 million suffers worldwide and this number is estimated to increase by more than 50% over the next ten years. Given that approximately 30% of diabetics develop kidney disease, there is an urgent need to identify new techniques for early identification of at risk patients and to discover and develop new treatment therapies to halt and regress kidney disease. Towards this end, my research has focussed intensively on the molecular processes which are altered in diseased kidneys compared with healthy kidneys. I have identified many key molecules which control development of renal disease including connective tissue growth factor (CTGF), bone morphogenetic protein-7 (BMP-7), and lysyl oxidase (LOX) proteins and have investigated the role of these factors in regulating pro-fibrotic processes such as epithelial injury and activation, extracellular matrix accumulation, cellular adhesion, migration, proliferation and apoptosis. My research employs a variety of pre-clinical models of kidney disease along with analysis of CKD patient samples. In addition, my studies have identified hypoxia, or insufficient oxygen, as a critical micro-environment which controls both pro-inflammatory and pro-fibrotic processes which are fundamental to kidney disease progression. Hypoxia, via activation of h ypoxia i nducible transcription f actors (HIF), regulates progression of kidney disease and I am currently examining how these pathways may be exploited in an effort to develop novel diagnostic and treatment strategies for DN.