Proteus Bacteria Cause Struvite and Calcium Carbonate Apatite Kidney Stones Through Urease Production
Proteus bacteria cause struvite (magnesium ammonium phosphate) and calcium carbonate apatite kidney stones through their production of the enzyme urease, which splits urea into ammonia and creates an alkaline urinary environment. 1
Mechanism of Stone Formation
The process of stone formation by Proteus species involves several key steps:
Urease Production: Proteus bacteria produce urease, an enzyme that hydrolyzes urea into ammonia and carbon dioxide 2
- This is the primary causative factor in infection stone formation
- Other urease-producing bacteria like Klebsiella can also cause similar stones 3
Alkalinization of Urine: The ammonia generated by urease activity raises urinary pH to alkaline levels (typically above 7.2)
Mineral Precipitation: In this alkaline environment, several changes occur:
- Magnesium, ammonium, and phosphate ions precipitate to form struvite crystals
- Calcium phosphate precipitates as calcium carbonate apatite
- These minerals become supersaturated in the alkaline urine 2
Biofilm Formation: Bacteria create an exopolysaccharide biofilm that:
- Incorporates mucoproteins and organic compounds
- Provides a matrix for crystal growth
- Protects bacteria from antibiotics 1
Stone Growth: The bacteria become incorporated within the stone structure, causing:
- Continuous infection inside the stone
- Progressive stone growth in a branched "staghorn" configuration
- Resistance to antibiotic treatment 1
Stone Composition and Characteristics
The stones formed by Proteus infection have specific characteristics:
- Primary composition: Magnesium ammonium phosphate (struvite) and calcium carbonate apatite 1
- Structure: Often grow in a "staghorn" or branched configuration, filling the renal pelvis and extending into calices 1
- Unique feature: Unlike other stone types, infection stones contain bacteria within their structure, making the stones themselves infected 1
- Clinical significance: If untreated, these stones can destroy kidney tissue and cause life-threatening sepsis 1
Treatment Approaches
For patients with struvite stones, treatment should focus on:
Complete stone removal to eradicate causative organisms, relieve obstruction, prevent further stone growth, and preserve kidney function 1
Surgical options include:
- Percutaneous nephrolithotomy (PNL)
- Combinations of PNL and shock wave lithotripsy (SWL)
- SWL monotherapy
- Open surgery in complex cases 1
Medical management:
Prevention of Recurrence
To prevent recurrence of infection stones:
- Aggressive management of Proteus and other urease-producing bacterial infections 5
- Complete removal of all stone fragments, as residual fragments can harbor bacteria 1
- Regular monitoring for recurrent infections
- Addressing risk factors such as urinary stasis or anatomical abnormalities
Clinical Pitfalls and Caveats
Residual fragments: Even small residual fragments after treatment can harbor bacteria and serve as a nidus for recurrent infection and stone growth 1
Antibiotic limitations: Antibiotics alone may not eradicate bacteria within stones due to the protective biofilm matrix 1
Urease inhibitors: While potentially helpful, medications like acetohydroxamic acid have significant side effects including headaches, abdominal discomfort, nausea, hair loss, shakiness, and anemia 4
Mineral composition: Changes in urinary mineral composition (especially magnesium, calcium, and phosphate) can significantly affect crystallization intensity in the presence of Proteus mirabilis 6
Recurrence risk: Struvite stones have a high recurrence rate, making follow-up and preventive measures essential 5