Zinc-enriched Pathological Biominerals in the Human Kidney Encode their Anatomical Microenvironments

Area of Science:

• Biomineralization
• Renal physiology
• Materials science

Background:

• Kidney stone formation mechanisms are poorly understood, hindering prevention and leading to high recurrence.
• Current models view stones as uniform masses from urine supersaturation, overlooking structural heterogeneity.
• Distinct renal microenvironments may influence stone composition and structure.

Purpose of the Study:

• To investigate if heterogeneous kidney biominerals preserve physicochemical signatures of their anatomical origin.
• To determine if spatial organization of zinc (Zn) reflects microenvironment-specific mineralization processes.
• To propose a new model for kidney stone formation based on anatomical and chemical heterogeneity.

Main Methods:

• Utilized a multiscale correlative microspectroscopy workflow to analyze biominerals from distinct renal niches.
• Characterized three morphologically distinct biominerals from papillary plaques, papillary stems, and collecting systems.
• Analyzed spatial gradients of zinc, calcium, phosphorus, and organic matrix components.

Main Results:

• Kidney stones exhibit marked structural and compositional heterogeneity across renal microenvironments.
• Papillary mineralization differs from collecting system stones; zinc is a spatially organized, region-dependent constituent.
• Identified conserved calcium and phosphorus nanoparticles, indicating shared nucleation units and a hierarchical mineralization model.

Conclusions:

• Kidney stones are complex, anatomy-specific biominerals encoding physicochemical microenvironment signatures.
• Zinc's spatial organization points to microenvironment-driven mineralization, challenging traditional supersaturation models.
• Targeting localized renal microenvironments offers potential for improved kidney stone prevention and therapy.