What type of renal stone is most commonly associated with estrogen therapy?

Calcium Oxalate Stones Are Most Commonly Associated with Estrogen Therapy

Estrogen therapy is most commonly associated with calcium oxalate stone formation, though estrogen actually has a protective effect against stone formation by lowering urinary calcium and calcium oxalate saturation.

Mechanism of Estrogen's Effect on Renal Stone Formation

• Estrogen appears to protect against kidney stone formation, as evidenced by the lower incidence of nephrolithiasis in women compared to men, with stone incidence rising after menopause 1
• Estrogen treatment in postmenopausal women leads to lower urinary calcium excretion (155 ± 62 vs. 193 ± 90 mg per day) and lower calcium oxalate saturation (5.07 ± 2.27 vs. 6.48 ± 3.44) compared to untreated postmenopausal women 1
• At the cellular level, estrogen reduces calcium oxalate crystal-binding capability of renal tubular cells by decreasing the expression of annexin A1 and α-enolase (known calcium oxalate crystal-binding receptors) on the cell surface 2
• Estrogen receptor beta (ERβ) specifically suppresses hepatic oxalate biosynthesis by upregulating glyoxylate aminotransferase (AGT1) expression and reduces oxalate-induced oxidative stress by transcriptionally suppressing NADPH oxidase subunit 2 (NOX2) 3

Risk Factors and Prevention of Calcium Oxalate Stones

• Factors contributing to calcium oxalate stone formation include fat malabsorption, increased bile salt-induced colonic permeability to oxalate, reduced bacterial degradation of oxalate, pyridoxine or thiamine deficiency, and hypocitraturia 4
• Prevention strategies for calcium oxalate stones include:
  • Maintaining adequate hydration to achieve urine volume of at least 2.5 liters daily 4
  • Following a diet low in oxalate (avoiding spinach, rhubarb, beetroot, nuts, chocolate, tea, wheat bran, strawberries) 4
  • Ensuring adequate dietary calcium intake rather than restriction 5
  • Reducing dietary fat and potentially replacing with medium chain triglycerides 4
  • Limiting sodium intake to less than 2,300 mg daily 4
  • Reducing non-dairy animal protein intake to 5-7 servings per week 4

Pharmacological Management of Calcium Oxalate Stones

• Potassium citrate therapy is recommended for patients with recurrent calcium stones who have low or relatively low urinary citrate excretion, or normal citrate excretion but low urinary pH 6
• Potassium citrate is preferred over sodium citrate because the sodium load in the latter may increase urine calcium excretion 7
• Thiazide diuretics are recommended for patients with high or relatively high urine calcium and recurrent calcium stones 4
• Thiazide dosages with hypocalciuric effect include hydrochlorothiazide (25 mg orally twice daily or 50 mg once daily), chlorthalidone (25 mg once daily), or indapamide (2.5 mg once daily) 4
• Allopurinol may be beneficial for patients with recurrent calcium oxalate stones who have hyperuricosuria and normal urinary calcium 4

Monitoring and Follow-up

• A 24-hour urine specimen should be obtained within six months of initiating treatment to assess response to dietary and/or medical therapy 4
• After initial follow-up, a single 24-hour urine specimen should be obtained annually or more frequently depending on stone activity 4
• Periodic blood testing is necessary to assess for adverse effects in patients on pharmacological therapy 4
• Repeat stone analysis should be obtained when available, especially in patients not responding to treatment 4

Special Considerations

• Patients with jejunum-colon anastomosis have a 25% chance of developing symptomatic calcium oxalate renal stones, primarily due to increased colonic absorption of dietary oxalate 4
• Estrogen treatment may decrease the risk of stone recurrence in postmenopausal women by lowering urinary calcium and calcium oxalate saturation 1
• Despite the protective effect of estrogen, when stones do form in patients on estrogen therapy, they are most commonly calcium oxalate stones 1, 2