Therapeutic potential of oxalate decarboxylase (OxDC) in the treatment of urolithiasis (kidney stone diseases)

Abstract

Kidney stone disease is a devastating medical condition that affects 12 % of the global population. The pathophysiology of renal stones is significantly influenced by calcium oxalate, which is present in most renal stones. Oxalate is obtained by humans from increasing dietary oxalate intake as well as from endogenous synthesis. High amounts of oxalate cause hyperoxaluria, which is a significant risk factor for recurrent nephrolithiasis. The available treatments for people with primary and secondary hyperoxaluria are insufficient and do not always result in a noticeable decrease in the excretion of oxalate in the urine. The best course of action for kidney stone treatment and prevention is to focus on the early stages of stone formation such as crystallization events. In recent years, enzymatic therapy has emerged as a viable alternative, notably the use of oxalate-degrading enzymes such as oxalate decarboxylase (OxDC). It is a Mn-dependent hexameric enzyme breaks down oxalate into carbon dioxide and formate, which helps dissolve and shrink CaOx stones that have already developed in the urinary system. The scientific community has recently become interested in OxDC due to its potential applications in biotechnology and medicine for the treatment of hyperoxalurias. Currently, oral delivery of this enzyme capable of digesting oxalate is being explored as a treatment option. This review investigates the therapeutic potential of OxDC in the treatment of kidney stone disease. It explores biochemical properties of OxDC, method of action and the results of preclinical and clinical trials to establish its efficacy and safety. The review also addresses the problems and future directions in the development of OxDC-based therapeutics, such as delivery modalities, stability and potential side effects.

Keywords: Calcium oxalate; Kidney stone; OxDC; Therapeutics; Urolithiasis.