Kidney stones and Microfluidics

Abstract

Kidney stones may be uncommon is certain parts of the world. On the other hand, considering the percentage of cases in the western world, one can say it is worrisome. Anyone can have kidney stones, which may be easily passed out of the kidney through the urine. It only becomes a cause for concern when the stones grow beyond a certain size. They can cause flank and abdominal pains, fever, painful urination, etc., and can subsequently result in kidney failure if the patient has only one kidney present. In that case, a kidney stone patient may require the attention of a nephrologist. Advancement in technology has provided conventional techniques such as ureteroscopy (URS), percutaneous nephrolithotomy (PNL) and shockwave lithotripsy (SWL) for treating kidney stones. One may wonder what exactly these stones are. They are nothing extraordinary but rather made of calcium oxalate (CaOx) crystals which are formed from a supersaturated urine. CaOx crystal which is a product of crystallization occurs in two forms, calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD). Crystallization is a very simple and effective purification and phase separation process used in the chemical and pharmaceutical industry. This process is usually influenced by many factors such as concentration, temperature, mixing, impurities, etc. The presence of oxalate in urine is a major contributor to the formation of kidney stones. High concentration of oxalate combines with calcium to form CaOx. On the other hand, injury to the kidney tubular epithelial cells results in the expression of Hyaluronic acid (HA). HA has since been considered as a binding agent which causes the retention of kidney stones. Furthermore, some scientists are of the idea that HA may also influence the formation of kidney stones. A novel method was developed to study the nucleation kinetics of CaOx in artificial urine under the influence of varying oxalate and HA concentrations. The method involved crystallizing CaOx (COM, COD) in emulsions (micro-droplets) that were generated by and stored in a microfluidic device. Incorporating polarized lightmicroscopy also allowed COM and COD to be detected at the same time. The cumulative probability distribution as a function of induction time for COM and COD was determined and fitted to the Weibull model. The induction time is the average time at which the first crystal is detected in the droplets. As was expected, higher oxalate concentration shortened the induction time for both COM and COD. Surprisingly, increasing HA concentration induced the formation of COM whiles inhibiting the formation of COD. In general, the frequency of COD was always less than that of COM. In conclusion, the idea that HA played a role in the formation of kidney stones was confirmed. This was the most important part of the research.