How to manage conditions associated with calcium phosphate and brushite in patients at risk of kidney stone disease or disorders of calcium and phosphate metabolism?

Management of Calcium Phosphate and Brushite Kidney Stones

Critical Recognition: Brushite Stones Require Aggressive Management

Patients with brushite (calcium phosphate dihydrate) stones face significantly higher treatment failure rates and require more intensive intervention than calcium oxalate stone formers, with ESWL rates 2-3 times higher due to stone resistance to shock wave lithotripsy. 1, 2

Stone Composition Matters: Key Clinical Distinctions

Brushite vs. Other Calcium Phosphate Stones

• Brushite stones are uniquely resistant to shock wave and ultrasonic lithotripsy, often requiring ballistic fragmentation for removal 2
• Patients with high calcium phosphate content (≥30%) receive significantly more ESWL treatments (1.86 vs 0.6 in men, 1.82 vs 0.73 in women) compared to calcium oxalate stone formers 1
• Brushite stone formers specifically require even more interventions (2.90 vs 1.02 in males, 3.11 vs 1.35 in females) 1

Rising Incidence Pattern

• Calcium phosphate stone prevalence has increased over three decades, particularly among women 1
• Some evidence suggests iatrogenic transformation from calcium oxalate to brushite stone disease may occur following shock wave lithotripsy-induced nephron injury 2

Urinary Chemistry: The Driving Forces

Primary Determinants of Calcium Phosphate Formation

• Stone formation rate correlates with urinary brushite saturation (r=0.22, p=0.01), NOT calcium oxalate saturation 3
• Brushite supersaturation is determined by urinary calcium (r=0.67, p<0.0001), phosphate, pH, and citrate (inverse correlation r=-0.3, p=0.0006) 3
• Urinary oxalate concentration does NOT correlate with brushite formation 3
• Urine pH and calcium phosphate supersaturation rise proportionally with stone calcium phosphate content in a dose-response manner 1

Underlying Metabolic Abnormalities

• High urine pH is the most common cause of calcium phosphate stones 4
• Incomplete or complete distal renal tubular acidosis presents with hyperchloremic acidosis, hypocitraturia, and persistently elevated urine pH 4
• Carbonic anhydrase inhibitors (acetazolamide, topiramate, zonisamide) create similar metabolic conditions 4

Treatment Algorithm

Step 1: Identify and Address Underlying Causes

• Measure urine pH on multiple occasions—persistently elevated pH (>6.5) suggests renal tubular acidosis or medication effect 4
• Obtain 24-hour urine collection measuring calcium, phosphate, citrate, pH, oxalate, and volume 3
• Review medications: discontinue carbonic anhydrase inhibitors if possible 4
• Screen for distal renal tubular acidosis with serum electrolytes, bicarbonate, and urine pH after acid load if indicated 4

Step 2: Fluid and Dietary Management

• Increase urine volume through aggressive hydration 4
• Restrict sodium intake to limit calcium excretion 4
• For calcium phosphate/brushite stones specifically: acidify urine using cranberry juice or betaine 5
• Control hypercalciuria as the primary target—urinary calcium concentration is the strongest determinant of brushite supersaturation 3

Step 3: Pharmacologic Intervention

Thiazide Diuretics (First-Line for Hypercalciuria)

• Thiazides lower urinary calcium excretion and are essential for calcium phosphate stone prevention 4
• Particularly important when using citrate supplementation to ensure safety 4

Citrate Supplementation (Use with Caution)

• Citrate therapy for calcium phosphate stones is controversial and requires careful consideration 4
• Potassium citrate increases urinary citrate, which inhibits calcium phosphate (brushite) nucleation 6
• However, citrate also raises urine pH (approximately 0.7 units at 60 mEq/day), which increases calcium phosphate supersaturation and may partially offset benefits 6, 4
• Only use citrate supplementation in calcium phosphate stone formers when combined with thiazide diuretics to counteract the pH-mediated increase in supersaturation 4
• Citrate is relatively ineffective when baseline urinary citrate is very low (<100 mg/day), as in severe renal tubular acidosis 6

Avoid Alkalinizing Strategies

• Do NOT alkalinize urine in calcium phosphate/brushite stone formers—this is the opposite of calcium oxalate management 5
• Calcium phosphate stones are more stable in alkaline urine 6
• Avoid high fruit and vegetable diets that alkalinize urine 5

Step 4: Monitoring and Follow-Up

• Serial 24-hour urine collections to assess treatment response 3
• Target urinary calcium reduction as primary goal 3
• Monitor urine pH—avoid persistent elevation above 6.5 4
• Despite aggressive medical management, brushite stone formers experience higher recurrence rates and often require repeated surgical interventions 2

Critical Pitfalls to Avoid

• Never treat calcium phosphate stones the same as calcium oxalate stones—the management strategies differ fundamentally 5
• Do not use citrate supplementation alone without thiazides in calcium phosphate stone formers 4
• Do not focus on oxalate restriction—oxalate does not drive brushite formation 3
• Recognize that brushite stones may represent iatrogenic disease from prior lithotripsy 2
• Anticipate treatment resistance and counsel patients about higher likelihood of recurrence and need for repeated interventions 1, 2

Special Considerations in CKD

• In CKD patients with calcium phosphate stones and hyperphosphatemia, restrict calcium-based phosphate binders 7
• Phosphate-lowering treatment should only be initiated for progressive or persistent hyperphosphatemia, not for prevention 7
• Excess calcium exposure may be harmful across all GFR categories of CKD 7
• Use non-calcium-based phosphate binders (sevelamer, lanthanum) as first-line therapy when phosphate lowering is needed 8