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Sergi Clotet-Freixas, PhD

Supervisor: Dr. Ana Konvalinka
Award: KRESCENT Post-Doctoral Fellowship
Institution: University Health Network
Year: 2019-2022

Study title: Sex and Human Kidney Metabolism: New Insights into Diabetic Kidney Disease

Dr. Sergi Clotet-Freixas completed his Bachelor of Biotechnology at the Universitat Autònoma of Barcelona (2010), and a Master’s degree in Biomedical Research at the University of Barcelona (2011). In 2012, he embarked on a PhD in basic science at the Hospital del Mar in Barcelona. The aim of his PhD was to explore the effect of sex on experimental diabetic kidney disease (DKD) and the renin-angiotensin system. Dr. Clotet-Freixas uncovered a critical role of androgens and a sex-specific role of angiotensin-converting enzyme 2 in DKD progression. These observations are relevant from a clinical perspective, as they may shed new light on sex-specific approaches to the treatment of DKD. As a PhD student, Dr. Clotet-Freixas also discovered a novel link between male sex hormones and impaired energy metabolism in the diabetic kidney, which may help to understand the more rapid kidney disease progression associated with male sex. Since completion of his PhD, he has been working as a post-doctoral fellow in the lab of Dr. Ana Konvalinka at the University Health Network in Toronto. Dr. Clotet-Freixas is continuing to study the role of cell sex and sex hormones on the metabolic function of renal tubular cells, and these studies have received funding support from CIHR Catalyst Grant. Dr. Clotet-Freixas is also expanding his expertise in other kidney-related disease settings by studying the mechanisms involved in antibody-mediated rejection, acute cellular rejection and acute tubular necrosis after kidney transplantation.
Lay Summary
Being a man is harder for the kidney than being a woman. Male sex predisposes to the development of several diseases affecting the kidney, known as chronic kidney disease (CKD). People with diabetes are at high risk of CKD as their kidneys are injured by high levels of glucose. These patients may develop diabetic kidney disease (DKD), the most predominant type of CKD. The harmful effect of male sex in DKD and CKD may be due to actions that the male sex hormones (known as androgens) exert on the kidney cells. However, researchers are still trying to discover what happens in kidney cells when they are in contact with androgens. Understanding how androgens are able to damage kidneys will allow the clinicians to apply more personalized treatments of kidney disease, depending on the patient’s sex.
Dr. Clotet-Freixas discovered that androgens affected the metabolism of kidney cells. Kidney cells with impaired metabolism may not be able to take up nutrients from their environment and use them to generate energy and work properly. Altered metabolism could be the reason why androgens are bad for the kidney. Metabolism is a very complex process based on the actions of many proteins that transform the nutrients to metabolites, used to make energy and build cellular machinery. He will study which of these proteins and the molecules that transport these proteins into the kidney cells are more implicated in the bad effects of androgens in the kidney. He will also study how estrogens (the female sex hormones) alter these processes in a different way, and may also predispose diabetic women to develop kidney diseases, but at a later moment and in a different fashion than men. In this project, he will discover proteins and processes through which androgens damage the kidneys faster and to a greater extent than estrogens, and propose how this can be stop, thus preventing CKD and DKD. The proposed research may lead to sex-specific therapies for kidney diseases.