Global Metabolomic Profiles of Autosomal Dominant Polycystic Kidney Disease in In-Vitro Renal Microcysts

Abstract

Autosomal-dominant polycystic kidney disease (ADPKD) is a progressive genetic disease characterized by the formation of bilateral fluid-filled cysts on the kidneys. It is one of the most common forms of chronic kidney disease (CKD), however little is understood about the mechanisms of cyst formation and propagation in renal cells. Madin-Darby Canine Kidney (MDCK) cells were cultured and stimulated with forskolin (FSK) to grow cysts in order to serve as in vitro models for metabolomic analysis of the pathways involved in the disease. LC-MS analysis and MetaboAnalyst testing revealed several dysregulated pathways between the experimental (n = 5; FSK+) and control (n = 5; FSK-) cohorts of MDCK cells. The most notable perturbed pathways revealed during metabolomic analysis include the carnitine shuttle, vitamin metabolism, the TCA cycle, fatty acid metabolism, and amino acid metabolism. The metabolites involved in these pathways may serve as potential targets for future therapeutic treatments of ADPKD. Results obtained from in vitro experiments demonstrate the value of using cell model systems for investigating the metabolic mechanisms of human disease.