Grant: CIHR New Investigator

Scarring is a major cause of organ failure, accounting for up to 50% of all deaths in the developed world. In the kidney, scarring is the final common pathway of damage activated by nearly all forms of chronic kidney disease. If left unchecked, kidney scarring can lead to kidney failure, an increasingly common, costly, and life-threatening condition requiring dialysis or kidney transplantation for survival. Unfortunately, clinicians have no safe and effective ways to diagnose or treat kidney scarring currently. Following injury and especially with scarring, organs stiffen. My lab has been working on ways to take advantage of this knowledge to better diagnose and treat kidney scarring, to identify those patients at highest risk for kidney failure and to treat these individuals with new anti-scarring treatments. In the first set of studies described in this application, we will take advantage of our discovery: (1) that fibroblasts, the main producers of kidney scar tissue, can sense stiffening after injury, and (2) that this stiffening makes them more sensitive to pro-scarring stimuli. We will explore how fibroblasts sense kidney stiffening, to develop new treatments that block the ability of fibroblasts to recognize that stiffening is occurring, and therefore that shut off the scarring process. In the second set of studies, we will take advantage of our recent development of new MRI techniques that can image the stiffness of a kidney without needles or surgery. Our goal is to test: (1) whether MRI measures of kidney stiffness are accurate, (2) whether they correlate with kidney scar measurements as determined by gold standard analysis of kidney biopsies, and (3) whether they predict if kidney function will decline. Given the importance of scarring to kidney disease, our expectation is that these studies, through improving the care of kidney scarring, will ultimately improve the lives of patients with kidney disease.