Chronic kidney disease (CKD) represents a global health burden with a prevalence >10% of the global population, projecting it to be the 5th leading cause of death by 2040. CKD can progress toward end-stage kidney disease (ESKD), requiring renal replacement therapy, i.e. dialysis and transplantation with high related risk of comorbidities and death for any cause and mostly for cardiovascular diseases.Kidney disease show a consistent sexual dimorphism. CKD progresses more fastly and kidney cancer is more frequent in males in comparison to females. By contrast, preeclampsia still represents the most frequent form of kidney disease allover the world, affecting 7% of pregnancies. The consequences of preeclampsia extend far beyond pregnancy, resulting in increased susceptibility to hypertension and CKD for the mother and the offspring. How sex influences kidney biology and cardiovascular risk is still largely unknown, with crucial gaps in CKD prevention and treatment. How sex influences kidney biology and cardiovascular risk is still largely unknown, with crucial gaps in CKD prevention and treatment.
We first identified kidney progenitors as crucial mediators of the kidney response to injury. In this project we propose that sexual dimorphism in kidney diseases may result from different response of renal progenitors to sex hormone in males and females. We also hypothesize that understanding the reason for these diversities may help unlocking crucial mechanisms for targeting preeclampsia, kidney cancer, CKD, and the related cardiovascular risk. For this reason, we plan to study the capacity of kidney progenitors to self-renew and differentiate into different kidney cell types during homeostasis and in conditions of pregnancy, ars well as in models of pre-eclampsia.
