Sex differences in blood pressure regulation
Hypertension is a global health challenge with known sexual dimorphism in pathophysiology and in responses to drug treatments, yet men and women are typically treated with the same approach. We conduct model simulations to gain mechanistic insights into how sex differences in the renin-angiotensin system and in renal phenotype impact kidney function in hypertension.
Simulating drug interactions in diabetes
Described as an "economic tsunami" by Diabetes Canada, diabetes has been projected to incur an annual cost of $16 billion in Canada by 2020. We seek to understand the sex differences and drug-drug interactions of key anti-hypertensive treatment (ACE inhibitors and ARB) and anti-hyperglycemic treatment (specifically, SGLT2 inhibitors).
A known complication of ACEi and ARB is hyperkalemia (high plasma potassium concentration). The impact of SGLT2i on potassium balance is controversial. Only one of the SGLT2i (canagliflozin) but not the other three (dapagliflozin, empagliflozin, ertugliflozin) mentions an increased risk of hyperkalemia in its official monograph. To what extent does SGLT2i modify the risk of hyperkalemia in diabetic patients with preserved versus impaired kidney function? What are the potential drug interactions between SGLT2i and ACEi/ARB? And are there sex differences?
Modeling integrative nephron function
With a unique 3D organization of functional units, the kidney is a complex organ. While much has been learned about the molecular processes occuring in specific cell types and nephron segments, little is known about the complex interplay that forms the basis for the integrity and function of the kidney.
Using computational modeling, our lab aim to better understand the kidney in health and disease.
Renal hypoxia in hypertension and diabetes
Despite intense research, the mechanism underlying the development of renal hypoxia and chronic kidney diseases remains incompletely understood.
Our lab develop computational models and conduct simulations to assess the following hypothesis: In diabetes and hypertension, oxidative stress reduces tubular transport efficiency and causes mitochondrial uncoupling, and thus gives rise to a mismatch between changes in renal oxygen supply and consumption, leading to renal hypoxia and eventually chronic kidney diseases. Furthermore, reduced NO formation increases tubular transport but reduces oxygen supply. In addition, tubular hypertrophy, Na+- glucose cotransport and hyperfiltration increase transport work in the diabetic kidney.