Review Article | Published:

Current insights into the mechanisms and management of infection stones

Abstract

Infection stones are complex aggregates of crystals amalgamated in an organic matrix that are strictly associated with urinary tract infections. The management of patients who form infection stones is challenging owing to the complexity of the calculi and high recurrence rates. The formation of infection stones is a multifactorial process that can be driven by urine chemistry, the urine microenvironment, the presence of modulator substances in urine, associations with bacteria, and the development of biofilms. Despite decades of investigation, the mechanisms of infection stone formation are still poorly understood. A mechanistic understanding of the formation and growth of infection stones — including the role of organics in the stone matrix, microorganisms, and biofilms in stone formation and their effect on stone characteristics — and the medical implications of these insights might be crucial for the development of improved treatments. Tools and approaches used in various disciplines (for example, engineering, chemistry, mineralogy, and microbiology) can be applied to further understand the microorganism–mineral interactions that lead to infection stone formation. Thus, the use of integrated multidisciplinary approaches is imperative to improve the diagnosis, prevention, and treatment of infection stones.

Key points

  • Urine chemistry has a key role in infection stone formation and is determined by the saturation conditions, pH, and the presence of modulators of crystallization and aggregation in the urine.

  • Organic substances associated with infection stones influence their physical characteristics (for example, hardness) and could also be involved in stone formation.

  • Struvite stones are associated with urinary tract infections and are formed as a result of biomineralization by urea-hydrolysing microorganisms.

  • Positive stone cultures suggest the association of bacteria with calcium-based stones; however, the role of bacteria (active or passive) in the lithogenesis of calcium-based stones requires further examination.

  • The development of microbial biofilms complicates renal conditions and treatments; biofilm mechanical stability and resistance to treatment is increased by the biomineralization process.

  • Infection stone management strategies should rely on the proper identification and characterization of stones and an understanding of stone formation, stone microbiology, and the influence of biofilms on stone characteristics.

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Acknowledgements

The authors acknowledge the support by the Montana University System Research Initiative (grant 51040-MUSRI2015-03) and the Burroughs Wellcome Fund (grant #1017519). The authors also thankfully acknowledge the helpful comments of three anonymous reviewers.

Review criteria

A review of the literature was performed by conducting searches in the Web of Science database (until March 2018). Search terms included “kidney/urinary stones”, “kidney/urinary stone characterization”, “kidney/urinary stone matrix”, “kidney/urinary stone biomineralization”, “mechanisms of kidney/urinary stone formation”, “management of kidney/urinary stones”, “mechanisms of resistance biofilm”, and “Proteus mirabilis”. No restriction on date of publication was used. The references of recent review articles were also searched to identify key studies related to urinary stones in the areas of chemistry, engineering, mineralogy, microbiology, and medicine. Additional papers were included based on recommendations by the peer reviewers.

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All authors researched data for the article, made substantial contributions to discussion of the article contents, wrote the manuscript, and reviewed and/or edited the manuscript before submission.

Correspondence to Dirk Lange or Robin Gerlach.

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Glossary

Supersaturation

The presence of a solute at a higher concentration in a solution than that of its own solubility.

Biofilms

Microorganisms attached to a surface and embedded in an extracellular polymeric substance matrix.

Randall’s plaque

Plaques of calcifications deposited in the interstitial tissue of the renal papilla.

Zeta potential

Measure of the magnitude of the electrostatic or charge repulsion or attraction between particles in colloidal systems.

Swarming motility

Rapid multicellular bacterial movement across solid surfaces powered by rotating flagella.

Planktonic bacteria

Bacteria that are freely floating in a suspension.

EPS matrix

Matrix of biopolymers comprised of extracellular polymeric substances (EPS) of microbial origin, in which biofilm microorganisms are embedded.

Quorum sensing

Mechanism of cell–cell communication by which bacteria might share information about cell density and regulate gene expression.

Reactive transport modelling

Computer models that integrate the use of chemical reactions with the transport of fluids.

Geochemical modelling software

Computer models that use thermodynamics and/or kinetics to analyse chemical reactions that affect geological systems.

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Fig. 1: Physicochemical process of stone formation.
Fig. 2: Role of microorganisms and biofilms in stone formation.