Caffeine effects on polycystic kidney disease development and progression, using a murine model Pkd1 cond/cond: Balcre

Abstract

Autosomal Dominant Polycystic Kidney Disease (ADPKD), caused by mutations on PKD1 and PKD2 genes, is one of the most common monogenic hereditary diseases in humans and is characterized by progressive substitution of renal tubules for cysts, progressing to end-stage renal disease (ESRD). In a cell culture study, utilizing cystic cells culture from ADPKD patients treated with caffeine, it has been demonstrated an increase in cAMP (adenosine 3,5- cyclic monophosphate) production, a mediator responsible for cellular proliferation and transepithelial cystic fluid secretion. However, caffeine administration to a non-ortholog ADPKD rat model couldn't be was not associated with cystic growth albeit increasing arterial pressure levels. At the same way, a recent study conducted in our service in 102 patients didn't demonstrate a correlation between caffeine intake and renal volume. Despite of the conflicting results, there has been a policy of restricting the consumption of caffeine for ADPKD patients. Since a clinical trial investigating the increase in caffeine supplementation is not feasible at the present moment, the aim of this project is to investigate caffeine effects on cysts growth, using an ortholog murine model (Pkd1cond/cond:Balcre), more similar to human disease. (AU)