Ursodeoxycholic Acid in Acute Kidney Injury
Ursodeoxycholic acid (UDCA) is not recommended for the prevention or treatment of acute kidney injury based on current clinical practice guidelines, and it may actually cause sodium retention and worsen fluid overload in certain patient populations.
Guideline-Based Recommendations
The major international guidelines for AKI management (KDIGO 2012) do not include UDCA among recommended therapies for preventing or treating AKI 1. The KDIGO guidelines specifically list agents that should NOT be used for AKI prevention or treatment, including:
- Low-dose dopamine (Level 1A recommendation against use) 1
- Fenoldopam (Level 2C recommendation against use) 1
- Atrial natriuretic peptide (Level 2C recommendation against use) 1
- Recombinant human IGF-1 (Level 1B recommendation against use) 1
UDCA is notably absent from any positive recommendations in established AKI guidelines 1.
Clinical Concerns with UDCA in AKI
Sodium Retention and Volume Overload
UDCA causes significant sodium retention in patients with renal dysfunction, which directly contradicts the management goals in AKI where volume overload is a major concern 2. In cirrhotic patients with refractory ascites:
- UDCA (15 mg/kg/day) significantly reduced sodium excretion (from 93±21 mmol/day to 35±8 mmol/day, P<0.05) 2
- This sodium retention occurred through increased reabsorption proximal to the distal tubule 2
- The effect was independent of hemodynamic changes, representing a direct nephron effect 2
Caution should be exercised in administering UDCA to any patient with fluid retention or AKI 2, as volume overload in AKI is associated with significantly higher mortality rates 3.
Experimental Evidence vs. Clinical Reality
While recent preclinical studies show potential protective mechanisms, these findings have not translated to clinical guidelines:
Preclinical Findings (Not Clinically Validated)
- In mouse models, UDCA (60 mg/kg/day) reduced sepsis-induced AKI through Nrf2/HO-1 pathway activation and NF-κB inhibition 4
- UDCA protected against cisplatin-induced AKI in mice by targeting ALDH1L2 and improving mitochondrial function 5
- Water-soluble UDCA prodrugs showed anti-apoptotic activity in vitro 6
Critical Gap
These experimental studies have not been validated in human clinical trials for AKI, and the sodium retention effect observed in humans 2 represents a significant safety concern that outweighs theoretical benefits.
Established AKI Management Priorities
Instead of UDCA, focus on evidence-based interventions:
Volume Management
- Use isotonic crystalloids (not colloids) for volume expansion in patients at risk for or with AKI (Level 1B recommendation) 1
- Avoid starch-containing fluids entirely 1, 3
- Use diuretics ONLY for managing volume overload, not for treating AKI itself (Level 2C recommendation) 1, 7
Nephrotoxin Avoidance
- Avoid aminoglycosides unless no suitable alternatives exist (Level 2A recommendation) 1
- Use azole antifungals or echinocandins rather than conventional amphotericin B when possible (Level 1A recommendation) 1
Hemodynamic Support
- Use vasopressors in conjunction with fluids for vasomotor shock (Level 1C recommendation) 1
Special Circumstance: Cholestatic Liver Disease
The only clinical context where UDCA might be considered near AKI is in cholestatic liver disease with concurrent renal dysfunction 8. However:
- This represents treatment of the primary cholestatic condition, not AKI treatment 8
- The sodium retention effect remains a concern 2
- Albumin (1 g/kg/day up to 100 g/day) is the preferred agent for preventing renal failure in liver disease patients with spontaneous bacterial peritonitis 1