Amphotericin B Deoxycholate in ESRD: Use with Extreme Caution and Prefer Alternatives
Amphotericin B deoxycholate should generally be avoided in patients with end-stage renal disease (ESRD) due to significant nephrotoxicity concerns, but it remains a viable option when lipid formulations are unavailable or unaffordable, particularly when administered intradialytically during hemodialysis sessions.
Key Evidence-Based Recommendations
Primary Approach: Lipid Formulations First
The most recent guidelines consistently prioritize lipid formulations of amphotericin B over the deoxycholate formulation in patients at risk for nephrotoxicity:
For histoplasmosis: Liposomal amphotericin B (3.0-5.0 mg/kg daily) is the preferred agent, with amphotericin B deoxycholate (0.7-1.0 mg/kg daily) relegated to "an alternative to a lipid formulation in patients who are at a low risk for nephrotoxicity" 1
For cryptococcal disease: Lipid formulations may be substituted for amphotericin B deoxycholate during induction phase in patients with significant renal disease 2
For mucormycosis: Amphotericin B deoxycholate (1-1.5 mg/kg/day) should be infused slowly over 6-8 hours with pre-medication and saline hydration (1L before and after) to minimize nephrotoxicity 3
When Deoxycholate Must Be Used in ESRD
Critical caveat: The ESCMID 2013 guidelines explicitly state a strong recommendation against the use of amphotericin B deoxycholate in adults with candidemia due to increased toxicity compared to better alternatives (DII recommendation) 4. However, real-world clinical practice, particularly in resource-limited settings, sometimes necessitates its use.
Intradialytic Administration Protocol
The most compelling evidence for amphotericin B deoxycholate use in ESRD comes from observational studies demonstrating safe intradialytic administration:
Dosing regimen 5:
- Maintenance dose: 0.5-1.0 mg/kg administered intravenously three times weekly during hemodialysis sessions
- Total cumulative doses: typically 500-1000 mg for most infections
- The drug is poorly dialyzable with both high-efficiency and high-flux membranes 6
Safety profile from clinical experience 5:
- Intradialytic hypotension occurred in 27.7% of HD sessions during amphotericin B treatment versus 28.8% of sessions before treatment (no significant difference)
- Fever >38.8°C developed in only 4 patients (1 episode per patient)
- Serum potassium, Kt/V, and urea reduction ratio remained stable
- All patients except one with AIDS resolved their fungal infections
Monitoring Requirements
When using amphotericin B deoxycholate in ESRD patients:
- Monitor serum electrolytes closely (particularly potassium and magnesium)
- Assess for infusion-related reactions (fever, chills, hypotension, tachypnea)
- Pre-medicate with antihistamines and corticosteroids to reduce acute reactions 7
- Monitor complete blood count and hepatic function
Special Considerations
Drug interactions in ESRD patients 7:
- Cyclosporine/tacrolimus: Paradoxically, patients receiving these agents with amphotericin B deoxycholate had lower renal toxicity rates (31%) compared to those not receiving immunosuppressants (8%)
- Avoid concurrent nephrotoxic agents (aminoglycosides, pentamidine) when possible
- Monitor for hypokalemia if patient is on digitalis glycosides
Financial constraints: A case report demonstrates successful treatment of histoplasmosis with deoxycholate amphotericin B in a patient with poor kidney function when liposomal formulation was financially inaccessible 8. The patient improved significantly after 12 days of treatment despite baseline renal impairment.
Clinical Decision Algorithm
- First-line: Always attempt to obtain lipid formulations (liposomal amphotericin B or amphotericin B lipid complex) for ESRD patients
- If lipid formulations unavailable: Consider amphotericin B deoxycholate administered intradialytically at 0.5-1.0 mg/kg three times weekly during HD sessions
- Contraindications to deoxycholate: Patients with concomitant nephrotoxic medications or those requiring rapid fungal clearance where treatment interruption is unacceptable
- Transition strategy: Switch to oral azole therapy (itraconazole, fluconazole) as soon as clinical improvement allows
Important Pitfalls
- Do not assume dialysis removes amphotericin B: The drug is poorly dialyzable, so standard dosing adjustments for dialyzable medications do not apply 6
- Avoid rapid infusion: Always infuse slowly over 6-8 hours to minimize infusion-related reactions 3
- Do not withhold treatment solely due to ESRD: When fungal infection is life-threatening and lipid formulations are unavailable, the mortality risk from untreated infection outweighs nephrotoxicity concerns in a patient already on dialysis 5
The evidence demonstrates that while amphotericin B deoxycholate is far from ideal in ESRD, it can be administered safely and effectively when given intradialytically with appropriate monitoring and supportive care 5, 6.