Do thiazide (thiazide diuretics) diuretics increase or decrease urinary citrate levels?

Thiazide Diuretics Decrease Urinary Citrate Levels

Thiazide diuretics decrease urinary citrate levels, which can worsen hypocitraturia in patients with kidney stones. 1 This effect is clinically significant enough that guidelines recommend potassium citrate supplementation when using thiazides for kidney stone prevention.

Mechanism and Evidence

Thiazide diuretics are commonly used to prevent recurrent calcium stones due to their ability to reduce urinary calcium excretion. However, they have several metabolic effects that can impact stone formation:

• Thiazides reduce urinary calcium excretion (hypocalciuric effect)
• They can induce or worsen hypocitraturia (decreased urinary citrate)
• They may cause hypokalemia, which further decreases urinary citrate

Research has demonstrated that thiazide treatment alone can reduce urinary citrate levels 2. This reduction in citrate is problematic because citrate is an important inhibitor of calcium stone formation - it complexes with calcium in urine, reducing the amount of free calcium available for stone formation.

Clinical Implications for Stone Management

The American Urological Association (AUA) recognizes this issue and recommends:

• Thiazide diuretics for patients with high or relatively high urine calcium and recurrent calcium stones 3
• Potassium supplementation (either potassium citrate or chloride) when thiazide therapy is employed 3
• Potassium citrate therapy for patients with recurrent calcium stones and low or relatively low urinary citrate 3

Combination Therapy Approach

For optimal management of recurrent calcium stones, particularly in patients with hypercalciuria:

1. Thiazide diuretics reduce urinary calcium excretion
2. Potassium citrate supplementation corrects or prevents thiazide-induced hypocitraturia
3. This combination provides superior protection against stone formation compared to thiazide alone

Studies have shown that patients who continued to form stones despite thiazide therapy had concurrent hypocitraturia, and adding potassium citrate (10-20 mEq three times daily) stopped stone formation in most patients 4.

Potassium Citrate vs. Potassium Chloride

When supplementing potassium during thiazide therapy:

• Potassium citrate is superior to potassium chloride for stone prevention 2

• Potassium citrate:

  • Corrects hypokalemia
  • Increases urinary pH and citrate levels
  • Enhances thiazide's ability to lower urinary calcium oxalate saturation
  • Reduces the propensity for spontaneous precipitation of calcium oxalate

• Potassium chloride:

  • Corrects hypokalemia
  • Does not increase urinary pH or citrate
  • Does not enhance the stone-preventing effects of thiazides

Safety Considerations

Despite theoretical concerns, long-term combined treatment with thiazides and potassium citrate:

• Does not lead to hypokalemia
• Does not cause hypochloremic metabolic alkalosis 5
• Is well-tolerated in most patients

Practical Recommendations

For patients with recurrent calcium stones requiring thiazide therapy:

1. Monitor urinary citrate levels before and during thiazide treatment

2. Consider adding potassium citrate supplementation, especially if:

   • Baseline hypocitraturia exists
   • Hypocitraturia develops during thiazide therapy
   • Stones continue to form despite adequate hypocalciuric response to thiazides

3. Typical dosages:

   • Thiazides: hydrochlorothiazide 25 mg twice daily or 50 mg once daily; chlorthalidone 25 mg daily; or indapamide 2.5 mg daily 3
   • Potassium citrate: 10-20 mEq three times daily 4

4. Continue dietary recommendations (sodium restriction, adequate calcium intake, high fluid intake) to maximize the effectiveness of pharmacological therapy 1

This combined approach effectively reduces stone recurrence by addressing multiple risk factors simultaneously - decreasing urinary calcium while maintaining adequate citrate levels.