Can Urso (ursodiol) cause proteinuria?

Ursodiol and Proteinuria: Evidence Assessment

Ursodiol (ursodeoxycholic acid) has not been documented to cause proteinuria as an adverse effect in clinical guidelines or research studies.

Mechanism of Action and Clinical Use

Ursodiol is primarily used for:

• Treatment of primary biliary cirrhosis
• Primary sclerosing cholangitis
• Dissolution of cholesterol gallstones
• Parenteral nutrition-associated cholestasis

The standard dosing is 13-15 mg/kg/day, with recommendations not to exceed 20 mg/kg/day due to potential adverse outcomes at higher doses 1.

Known Adverse Effects of Ursodiol

Common adverse effects of ursodiol include:

• Gastrointestinal symptoms (diarrhea, nausea)
• Headache
• Rash
• Fatigue

Notably, proteinuria is not listed among the documented adverse effects in clinical guidelines or research studies on ursodiol 1, 2, 3, 4.

Medications Known to Cause Proteinuria

While ursodiol is not associated with proteinuria, several other medications are known to potentially cause or exacerbate proteinuria:

1. Bisphosphonates: Medications like pamidronate and zoledronic acid have been documented to cause albuminuria, with recommendations for monitoring urinary protein in patients receiving these medications 5

2. Immunosuppressive drugs: Some immunosuppressants used in transplant patients, such as cyclosporine, can affect kidney function and potentially cause proteinuria 5

Clinical Approach to Suspected Drug-Induced Proteinuria

If a patient on ursodiol develops proteinuria, consider:

1. Rule out other causes:

   • Glomerular diseases
   • Diabetic nephropathy
   • Hypertensive nephrosclerosis
   • Other medications known to cause proteinuria

2. Assess severity:

   • Quantify proteinuria with 24-hour urine collection or spot urine protein-to-creatinine ratio
   • Significant proteinuria is generally defined as ≥500 mg/24 hours 5

3. Monitor kidney function:

   • Check serum creatinine and estimated GFR
   • Monitor for other signs of kidney injury

Management Considerations

If proteinuria occurs in a patient taking ursodiol:

1. Evaluate for alternative causes before attributing to ursodiol
2. Consider nephrology consultation for persistent unexplained proteinuria
3. Implement standard proteinuria management as recommended by KDIGO guidelines, including:
   • ACE inhibitors or ARBs for persistent proteinuria 5
   • Sodium restriction (<2.0 g/day) 5
   • Appropriate diuretic therapy if edema is present 5

Conclusion

Based on available evidence, ursodiol has not been documented to cause proteinuria. If proteinuria develops in a patient taking ursodiol, clinicians should investigate other more likely causes before attributing it to ursodiol therapy.