Investigation the role of bacteria in calcium oxalate kidney stone formation.

Abstract

Kidney stone disease is a serious health concern, with a high incidence rate of approximately 10% among North Americans and a high economic burden on the medical system exceedingly over $5 billion per year. Approximately 80% of kidney stones are composed of calcium oxalate (CaOx). While there are options for medical and surgical management of kidney stone disease, unfortunately, so far, no treatment has been developed to treat the cause of CaOx stone formation effectively. Thus, the rate of recurrence is high.(Lotan Y 2007) Recently, emerging clinical studies suggested that bacteria may play a critical role in stone formation, although the mechanism is not adequately studied (An et al. 2021). This study aims to investigate the role of bacteria in CaOx kidney stone formation and propagation. We hypothesize that inside the urinary tract, bacteria mediate the biocrystallization of CaOx, leading to the formation and development of kidney stones. Here, we will in-vitro study CaOx bacterial-induced crystallization using our developed microfluidic kidney model and under a continuous flow of artificial urine to mimic the unique physiological microenvironment of the urinary tract. In this regard, we will manipulate, monitor, and analyze the number, size, and morphology of the formed CaOx crystals in the presence of bacteria and under various urinary conditions (e.g., flow rate, pH, and chemistry) using high-resolution live microscopic, imaging, and spectroscopic approaches. Furthermore, we will elucidate the dominant molecular mechanism underlying the formation and propagation of CaOx stones at the single-bacterium level with a focus on the effect of bacterial secretion and sensing appendages.Investigation of the interaction at single and multi-cell levels allows us to accurately capture early aspects of the biocrystallization capabilities of bacteria.