FEATURE
Accelerating the Discovery of
Anti-Fibrotic Therapies for Chronic Kidney Disease
By Alexa Desimone
F
Dr. Richard E. Gilbert, an endocrinologist at St. Michael’s Hospital in Toronto, has dedicated his professional career to identifying therapeutic strategies for the prevention and treatment of chronic fibrotic disorders, focussing predominantly on CKD and heart failure. He is particularly interested in these disorders in the diabetic setting given that diabetes is present in approximately 30-50% of all patients with either heart failure or CKD. Dr. Gilbert is a Tier 1 Canada Research Chair in Diabetes 10 | IMS MAGAZINE WINTER 2020 NEPHROLOGY
Growing up in Adelaide, a small city in South Australia, Dr. Gilbert completed his medical training at Flinders University. Excited by the prospect of continuing in clinical medicine while also pursuing his research interests, he accepted an offer as a one-year lecturer at London University in London, England. As Dr. Gilbert described, “The salary was barely enough to live on but the opportunity it afforded me in the academic, social and societal spheres was immeasurable”. This was a pivotal moment in Dr. Gilbert’s career. Rather than staying on a predictable and linear path, he made a bold choice that would enrich his academic and life experiences. Returning to Australia, he completed his medical fellowship and doctoral studies in the clinical and molecular aspects of diabetic kidney disease and established a highly productive research laboratory at St. Vincent’s Hospital in Melbourne, Australia. But it was time for Dr. Gilbert to broaden his horizons once again by seeking to do a sabbatical in Toronto where his wife, Susan, was from. Rather than offers for his intended sabbatical, Dr. Gilbert was invited to apply for newly available clinician-scientist positions at two University of Toronto institutions. “Coming to a city with such great research, collegiality, and collaboration made the decision easy” said Dr. Gilbert. So, in 2006 he set up his laboratory and took
up his post at St. Michael’s Hospital as a clinician-scientist. The pathogenesis of diabetic kidney and heart disease, encompassing both glucose-dependent and glucoseindependent pathways, requires a multifaceted approach to establish therapeutic strategies.⁶ In the kidney, fibrosis impairs filtration and tubular cell function, whereas in the heart, it impairs both systolic and diastolic function with stiffening and impaired contractility of Photo sourced from St. Michael’s Hospital
ibrotic disorders are becoming increasingly prevalent; they take many forms and are often life threatening. It is estimated that fibrosis accounts for almost half the chronic diseases afflicting industrialised countries.1 Chronic kidney disease (CKD) is one of the most devastating and common examples of fibrotic disease.2,3 In the kidney, fibrosis is characterized by the accumulation of extracellular matrix proteins, typically in the glomerulus and tubulointerstitium, which inevitably infringes on nearby structures, resulting in hypoxia, tubular atrophy, and inflammatory cell infiltration.4 With time, the formation of fibrotic lesions leads to irreversible end-stage kidney failure. Unfortunately, four million Canadians are currently living with CKD, with the majority requiring dialysis or kidney transplantation.5 Despite its prevalence, therapeutic strategies targeting profibrotic mechanisms in CKD are lacking.
Complications, Professor of Medicine at the University of Toronto, and Head of the Division of Endocrinology at St. Michael’s Hospital/Unity Health Toronto.
DR. RICHARD E. GILBERT MD, FRCPC, FRACP, FACP, FASN, PhD Professor of Medicine, University of Toronto Head of the Division of Endocrinology, St. Michael’s Hospital Canadian Research Chair in Diabetes Complications
