Mimicking Kidney Stone Formation

Abstract

Nephrolithiasis is a disease of the urinary tract system, caused by accumulating waste products which form small stones. It is known to affect people all over the world, with a prevalence in populations as high as 16.7 % in North East Thailand and 18.5 % in uranium workers in Eastern Tennessee, USA. The most found stones are Calcium (𝐶𝑎)Oxalate (𝑂𝑥)based crystals, which form when their concentrations are supersaturated in the kidney, thus exceeding their solubility limit. The most common forms of CaOxcrystals in urine are the stable Calcium Oxalate Monohydrate (COM) and the metastable Calcium Oxalate Dihydrate (COD). If they grow too large and get stuck, medical surgery is necessary to prevent kidney failure. It is therefore necessary to understand this form of biomineralization within the human body to ensure proper treatment and prevention. This study focuses on mimicking the situation in the collecting duct of the kidney. This is done in a 295𝑥45 𝜇𝑚T-shaped microchannel, wherin a 𝐶𝑎solution enters through one inlet and an 𝑂𝑥solution through a second, such that the combined fluid flowing through the main channel is supersaturated. 𝐶𝑎 and 𝑂𝑥 are dissolved in either water or artificial urine based on the works of Streit et al. In this manner, the following effects are studied: the effect of varying average velocity, the effect of adding an amount of the natural inhibitor Osteopontin in the 𝑂𝑥-inlet, and the effect of changing the 𝐶𝑎 to 𝑂𝑥 ratio in urine conditions. Besides the microfluidic experiments, three models are applied to understand the ongoing phenomena: the Surface Reaction Model (SRM)as an analytical model of the transport-reaction kinetics at the crystal surface, the Analytical Microchannel Model (AMM) as an analytical model of the momentum and mass transport through the microchannel, and the COMSOL model as a numerical model of the microchannel made in the Matlab program COMSOL. With the latter momentum and mass transport through the channel are calculated and the mass transport results are combined with Jess Urine Expert to calculate supersaturation profiles at the channel bottom, where the crystals grow. The number for the transport reaction kinetics of the crystal surface points out that the surface reaction limits the growth, not the mass transport. LowDamköhler numbers for the transport-reaction kinetics in the entire microchannel also point this out.