Identifying pathways of injury and resolution in the kidney

Chronic kidney disease (CKD) is a risk factor for the development of end-stage kidney disease and cardiovascular disease. In CKD ongoing injury and attempts at self-repair occur simultaneously in the kidney, with disease progressing when the injury exceeds the ability of the kidney to repair. We are using a number of novel pre-clinical models and state-of-the-art technologies to identify pathways that may promote kidney injury or repair, so that we can develop therapies that favour regression of kidney disease.

Research Methods and Objectives

We have developed two pre-clinical models of injury and repair in the kidney. Firstly, induction of diabetes and hypertension in a transgenic rodent promotes renal injury and activates similar pathways to those observed in the human diabetic kidney. Tight control of blood glucose and blood pressure in this model switches off genes implicated in renal scarring, while many more genes remain switched on, potentially to promote repair. We have found that similar gene pathways are activated in injury and repair in a second pre-clinical model, reversible obstructive uropathy. We are currently using state-of-the-art techniques including fluorescence-assisted flow cytometry, RNA sequencing and single-cell RNA sequencing to understand the injury and repair pathways activated in specific types of cell within the kidney. Through a better understanding of the molecules that promote injury and repair, we hope that we can develop novel therapies that can reduce injury and enhance the reparative capacity of the kidney.

Our work has been published in the American Society of Nephrology, Kidney International and Nephrology and has been funded by the Scottish Chief Scientist Office, Kidney Research UK and the British Heart Foundation

Combination of 3 images of the kidney (normal, scarred, resolution of scarring) along with 3 gene clustering graphs

Principal Investigator, Co-Investigators, Other researchers

This is a collaborative research project including Dr Bryan Conway, Dr Laura Denby, Carolynn Cairns (all Centre for Cardiovascular Science), Professor Jeremy Hughes (Centre or Inflammation Research), Dr Tamir Chandra (Institute of Genetics and Molecular Medicine).