Proposal for pathogenesis-based treatment options to reduce calcium oxalate stone recurrence

Area of Science:

• Nephrology
• Biochemistry
• Pharmacology

Background:

• Kidney stone disease prevalence is rising globally, with high recurrence rates (30-50%).
• Current treatments focus on reducing urinary mineral supersaturation, but other stone formation pathways exist.
• Idiopathic calcium oxalate stones involve Randall's plaques, with oxidative stress and specific molecular pathways implicated in their formation.

Purpose of the Study:

• To review experimental studies on readily available compounds for kidney stone recurrence prevention.
• To explore novel therapeutic targets beyond supersaturation reduction.

Main Methods:

• A literature review of relevant studies up to October 2020 was conducted.
• PubMed was used as the primary database for literature searches.

Main Results:

• Experimental studies indicate the involvement of reactive oxygen species, oxidative stress, the renin-angiotensin-aldosterone system (RAAS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and the NLRP3 inflammasome in stone pathogenesis.
• Compounds like statins and angiotensin-converting enzyme inhibitors have shown potential in reducing calcium oxalate nephrolithiasis in animal models.

Conclusions:

• Beyond standard therapies, antioxidants, free radical scavengers, and inhibitors of NADPH oxidase, NLRP3 inflammasome, and RAAS may offer benefits for stone prevention.
• While human clinical evidence is limited, experimental data support considering these agents alongside conventional treatments for patient counseling.