Urinary stone formation: Dent's disease moves understanding forward

Area of Science:

• Nephrology
• Cell Biology
• Biochemistry

Background:

• Renal stones form in the collecting duct due to complex interactions of urine components and epithelial cells.
• Physiological feedback mechanisms sensing the luminal environment normally limit crystal formation.
• Epithelial cell adhesion and intracellular crystal processing are newly recognized mechanisms for controlling crystal growth.

Purpose of the Study:

• To discuss newly discovered physiological controls that limit renal crystal formation.
• To explore the role of epithelial cell interactions in renal stone pathogenesis.
• To examine Dent's disease as a model for renal tubular disorders leading to stone formation.

Main Methods:

• Review of physiological controls for crystal formation.
• Analysis of epithelial cell adhesion and intracellular crystal processing.
• Discussion of endosomal acidification defects in Dent's disease.

Main Results:

• Newly identified feedback mechanisms sense the luminal environment to limit crystal formation.
• Epithelial adhesion and intracellular crystal processing represent a previously unrecognized mechanism for limiting crystal growth.
• Defects in endosomal acidification, specifically the CLC-5 channel, disrupt endosomal traffic and cause stone formation in Dent's disease.

Conclusions:

• Understanding epithelial cell interactions and feedback controls is crucial for comprehending renal stone formation.
• Disruptions in these mechanisms can lead to kidney stone disease.
• Defects in CLC-5 related endosomal acidification are a key factor in Dent's disease and associated nephrolithiasis.