The researchers pictured above will be working on projects supported by the CRAFT Project Awards. Clockwise, starting from top-left hand corner: Claudia dos Santos (U of T), Keith Morton (NRC), Amy Wong (U of T), Daniel Brassard (NRC), Edmond Young (U of T) and Lidija Malic (NRC).

Left: Microscope image of male proximal tubular epithelial cells. Right: Dr. Ana Konvalinka. Readers may view, browse, and/or download material for temporary copying purposes only, provided these uses are for noncommercial personal purposes. Except as provided by law, this material may not be further reproduced, distributed, transmitted, modified, adapted, performed, displayed, published, or sold in whole or in part, without prior written permission from the publisher.

CRAFT Publication: Mechanisms underpinning sex differences in kidney disease.

A team led by CRAFT researcher and Clinician Scientist, Dr. Ana Konvalinka, has elucidated sex-based differences in the kidney metabolism of men and women with diabetes. These differences could help explain why diabetic kidney disease is more prevalent and progresses faster in men than in women.

The findings, reported in the prestigious journal Science Translational Medicine, were obtained by examining the molecular and physiological features of primary proximal tubular epithelial cells from the kidneys of healthy men and women. Some of these studies were enabled through the use of an innovative microfluidic platform that cultured and perfused up to 128 independent cell samples in a 384-well plate, through collaboration with Dr. Boyang Zhang from McMaster University. In addition, the findings were supported by studies in preclinical models of diabetes and blood analyses from adults and adolescents living with diabetes.

The study and its findings indicate the existence of fundamental mechanisms that protect women against kidney disease, and others that predispose men to kidney disease. A better understanding of kidney sex differences will facilitate the development of sex-specific predictive tools and treatments for kidney diseases. One of these tools, which is currently under development at CRAFT, is a kidney-on-chip model that will more accurately recapitulate human kidney function in healthy and diseased states, and in specific patients living with kidney disease.

Publication: Clotet-Freixas S, et al. Sex differences in kidney metabolism may reflect sex-dependent outcomes in human diabetic kidney disease. Sci Transl Med. 2024 Mar 6. doi: 10.1126/scitranslmed.abm2090