Examining the role of intra-renal hypoxia in chronic kidney disease

To make any breakthroughs in finding a cure for chronic kidney disease (CKD), there is an urgent need to obtain a better and more detailed understanding of the cause(s) and mechanisms underlying the progression from minor loss of function to complete renal failure. We hypothesize that an inefficient oxygenation of kidney tissue, i.e. hypoxia, plays a major role leading to increased renal sympathetic outflow thereby driving and/or exacerbating CKD progression. Using unique technology we investigate the temporal sequence of events that lead to reduced kidney oxygenation in a rat model of CKD. This temporal profiling will reveal causation that will contribute to optimising appropriate, and novel, treatment strategies relative to disease progression.

Project Outline
The aim of this studentship is to characterize the temporal relationships between tissue hypoxia, blood flow, high sympathetic nerve activity (SNA) and progression of CKD. With this information we will be able to move beyond demonstration of association of renal hypoxia, high SNA and CKD, to demonstrate causation. In addition the studentships will investigate to what extent interruption of either afferent or efferent SNA can be antihypertensive and renoprotective. To translate the expected findings this studentship will therapeutically target renal hypoxia specifically in CKD, making it a very promising and timely subject.

Maarten Koeners’ laboratory has excellent core research facilities and post-doctoral support. This PhD will provide exposure and training in experimental approaches including micro-surgery, radio-telemetry, electro-physiology, renal function assays, imaging and pharmacology with an emphasis on the integration of these skills. In addition the laboratory is a participant of the Carpediem consortium (EU funded staff exchange scheme) which will allow the PhD student to travel to overseas University(s) for a finite period of time (months) to learn additional skills/techniques. These include for molecular biology (University of Tokyo), large animal models (University of Auckland) and computational modelling (Monash University).