Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Surgery

Supervisor

Razvi, Hassan

2nd Supervisor

Burton, Jeremy

Co-Supervisor

3rd Supervisor

Bjazevic, Jennifer

Co-Supervisor

Abstract

The pathogenesis of infectious kidney stones is poorly understood, while equally unclear is the role of urinary modulators and bacteria. An experimental model was created and utilized to test a variety of urinary modulators and bacterial strains commonly associated with struvite and calcium phosphate stones to evaluate their potential roles in influencing crystal formation. Modulators such as acids, citrate, and osteopontin had strong inhibitory effects on infectious crystal formation while the remaining modulators had neutral, mixed, or positive effects. Lastly, it was determined that the presence of urease may not directly lead to calcium phosphate and struvite stones in all cases, and in the absence of urease, bacteria may promote calcium phosphate stone formation. Ultimately, this model will help to provide researchers with the ability to rapidly test a wider range of urinary modulators with infectious kidney stone formation and how they relate to individual bacterial species.

Summary for Lay Audience

Kidney stones will affect about 10-11% of the population at some point during their lifetime and that rate appears to be increasing. As this is a common condition, it has a significant financial impact on the healthcare system. There are different types of kidney stones, but only two associated with urinary tract infections, struvite and calcium phosphate stones. Struvite and calcium phosphate stones represent about 10-15% of stones in patients, however, their clinical importance cannot be understated. The occurrence of these stones can lead to recurrent infections, sepsis, and even death. They also tend to have a higher recurrence rate than the more common calcium oxalate stones and typically require surgical management.

Researchers’ understanding of kidney stone development has improved over recent history, but a lot is still yet to be uncovered. One question that eludes researchers is how certain stones commonly associated with urinary tract infections, such as calcium phosphate, can form even in the absence of an infection. Furthermore, researchers believe there must be more to the equation in understanding how struvite or calcium phosphate stones can form even in the presence of an infection. Several proteins and substances in the urine are thought to play a role in the development of these stones and discovering their mechanism will have major clinical implications. Using a novel high-throughput laboratory model with artificial urine, the following document outlines our approach in testing a high number of these modulators and select bacterial strains to see their effect on infectious stone formation.

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