Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Surgery

Supervisor

Leong, Hon S.

2nd Supervisor

Razvi, Hassan

Joint Supervisor

Abstract

Nephrolithiasis involves the supersaturation of a stone-forming solute in urine leading to the formation of a calculus. The development of novel therapeutic agents for this multifactorial urological disorder has been hindered by lack of a practical pre-clinical model. Currently established medical treatments can possess unfavorable side effect profiles and inconsistent efficacies in certain metabolic milieus. Here, Drosophila melanogaster ̶ an emerging model for calcium oxalate nephrolithiasis ̶ was investigated as a potential disease model and high throughput drug discovery platform for human uric acid nephrolithiasis. Through disruption of the Uro gene and purine-rich dietary manipulation, we successfully demonstrate the formation of uric acid calculi in fly malpighian tubules as confirmed by ex vivo confocal microscopy, qRT-PCR and scanning electron microscopy. Flies treated with standardized concentrations of drug candidates through a novel assay identified several compounds with potential anti-lithogenic effects underscoring the power of D. melanogaster as a high throughput tool in drug screening for nephrolithiasis.

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