What are the current treatments for nephrocalcinosis?

Treatment of Nephrocalcinosis

The treatment of nephrocalcinosis should focus on addressing the underlying cause while implementing measures to prevent further calcium deposition, reduce hypercalciuria, and preserve renal function.

Underlying Causes and Diagnosis

Before initiating treatment, it's essential to identify the underlying cause of nephrocalcinosis, which commonly includes:

• Hereditary tubulopathies (48% of cases) 1
• Hyperoxaluria (35% of cases) 1
• Vitamin D excess (5% of cases) 1
• Distal renal tubular acidosis 2
• Dent disease 2
• Idiopathic hypercalciuria 2
• Prematurity-related factors in neonates 3

Treatment Approaches

1. Conservative Management

• Hydration: Maintain high fluid intake to reduce urinary concentration of calcium and oxalate
• Dietary Modifications:
  • Limit sodium intake to reduce urinary calcium excretion
  • Moderate calcium restriction (400-800 mg/day) for patients with hypercalciuria 4
  • Reduce oxalate intake by limiting nuts, dark roughage, chocolate, and tea 4

2. Pharmacological Management

• Potassium Citrate:

  • First-line therapy for most forms of nephrocalcinosis
  • Mechanism: Increases urinary citrate, which complexes with calcium and decreases calcium ion activity, inhibits spontaneous nucleation of calcium oxalate and calcium phosphate 4
  • Dosage: 30-100 mEq per day, typically 20 mEq three times daily 4
  • Efficacy: Produces a sustained increase in urinary citrate from subnormal to normal values (400-700 mg/day) and increases urinary pH from 5.6-6.0 to approximately 6.5 4

• Thiazide Diuretics:

  • For hypercalciuria-related nephrocalcinosis
  • Reduces urinary calcium excretion by enhancing calcium reabsorption in the distal tubule

• Hydrochlorothiazide:

  • Decreases calciuria in patients with X-linked hypophosphatemia (XLH) 5
  • Can be used in other forms of nephrocalcinosis to reduce hypercalciuria

3. Disease-Specific Treatments

For Primary Hyperoxaluria:

• RNA interference therapies for type 1 primary hyperoxaluria (PH1) 5
• Vitamin B6 (pyridoxine) for responsive cases of PH1

For X-linked Hypophosphatemia:

• Combination of oral phosphorus and active vitamin D (calcitriol or alfacalcidol) 5
• To prevent nephrocalcinosis in XLH:
  • Keep calciuria levels within normal range
  • Avoid large doses of phosphate supplements
  • Ensure regular water intake
  • Consider potassium citrate administration
  • Limit sodium intake 5

For Distal Renal Tubular Acidosis:

• Alkali therapy with potassium citrate to correct metabolic acidosis and increase urinary citrate

Monitoring and Follow-up

• Regular monitoring of renal function
• Periodic imaging to assess progression or resolution of nephrocalcinosis
• Urinary parameters monitoring:
  • Urinary calcium, oxalate, citrate levels
  • Urinary pH
  • Urinary supersaturation of stone-forming salts

Prognosis and Complications

Without appropriate treatment, nephrocalcinosis can lead to progressive renal damage. In a study with a median follow-up of 38 months, estimated glomerular filtration rate decreased from 84.0 to 68.2 mL/min/1.73 m² (P = 0.001) 1.

Common Pitfalls and Caveats

• Diagnostic confusion: Nephrocalcinosis must be distinguished from nephrolithiasis (kidney stones), as treatment approaches may differ 6
• Delayed diagnosis: Nephrocalcinosis is often detected incidentally and may represent a serious metabolic defect 7
• Potassium citrate limitations: May be relatively ineffective in patients with severe renal tubular acidosis or chronic diarrheal syndrome where urinary citrate is very low (<100 mg/day) 4
• Vitamin D caution: Excessive vitamin D supplementation can contribute to nephrocalcinosis and should be carefully monitored

Special Considerations

• In neonates: Nephrocalcinosis occurs in up to 40% of preterm infants and requires specific evaluation and management 3
• In chronic kidney disease: Treatment must be adjusted based on renal function, with careful monitoring of electrolytes and acid-base status
• In primary hyperparathyroidism: Address the underlying hormonal imbalance while managing nephrocalcinosis

By addressing the underlying cause and implementing appropriate preventive measures, progression of nephrocalcinosis and subsequent renal damage can be minimized or prevented in many cases.