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Updated: Jul 20, 2025
Estimation of Urinary Nanocrystals in Humans using Calcium Fluorophore Labeling and Nanoparticle Tracking Analysis
Published on: February 9, 2021
Proposal for pathogenesis-based treatment options to reduce calcium oxalate stone recurrence
Saeed R Khan1, Benjamin K Canales2
1Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
Objective:
Prevalence of kidney stone disease continues to increase globally with recurrence rates between 30% and 50% despite technological and scientific advances. Reduction in recurrence would improve patient outcomes and reduce cost and stone morbidities. Our objective was to review results of experimental studies performed to determine the efficacy of readily available compounds that can be used to prevent recurrence.
Methods:
All relevant literature up to October 2020, listed in PubMed is reviewed.
Results:
Clinical guidelines endorse the use of evidence-based medications, such as alkaline agents and thiazides, to reduce urinary mineral supersaturation and recurrence. However, there may be additional steps during stone pathogenesis where medications could moderate stone risk. Idiopathic calcium oxalate stones grow attached to Randall's plaques or plugs. Results of clinical and experimental studies suggest involvement of reactive oxygen species and oxidative stress in the formation of both the plaques and plugs. The renin-angiotensin-aldosterone system (RAAS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, mitochondria, and NOD-like receptor pyrin domain containing-3 (NLRP3) inflammasome have all been implicated at specific steps during stone pathogenesis in animal models.
Conclusion:
In addition to supersaturation-reducing therapies, the use of anti-oxidants, free radical scavengers, and inhibitors of NADPH oxidase, NLRP3 inflammasome, and RAAS may prove beneficial for stone prevention. Compounds such as statins and angiotensin converting enzyme inhibitors are already in use as therapeutics for hypertension and cardio-vascular disease and have previously shown to reduce calcium oxalate nephrolithiasis in rats. Although clinical evidence for their use in stone prevention in humans is limited, experimental data support they be considered along with standard evidence-based medications and clinical expertise when patients are being counselled for stone prevention.
Insights
Kidney stone recurrence is common. Experimental studies suggest antioxidants and RAAS inhibitors may help prevent stones by targeting oxidative stress and inflammation, complementing standard therapies.
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.
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