What is the difference in nephrotoxicity among amphotericin B (antifungal medication) formulations?

Nephrotoxicity Differences Among Amphotericin B Formulations

Amphotericin B deoxycholate (AmB-d) is significantly more nephrotoxic than all lipid formulations, causing acute renal failure in up to 50% of recipients, while lipid formulations reduce this risk substantially. 1

Ranking of Nephrotoxicity (Most to Least Toxic)

1. Amphotericin B Deoxycholate (AmB-d) - Most Nephrotoxic

• Causes acute renal failure in up to 50% of recipients, making it the most nephrotoxic formulation 1
• Results in nephrotoxicity through direct tubular damage and renal vasoconstriction 2
• Should be reserved only for resource-limited settings where alternatives are unavailable 3
• Causes hypokalemia in up to 80% of patients due to selective distal tubular epithelial toxicity 3

2. Amphotericin B Colloidal Dispersion (ABCD) - Intermediate Toxicity

• Less nephrotoxic than AmB-d but has frequent and severe immediate infusion reactions comparable to conventional amphotericin B 4
• Has the poorest tolerability profile among lipid formulations 5

3. Amphotericin B Lipid Complex (ABLC) - Lower Toxicity

• Considerably less nephrotoxic than AmB-d with improved general and renal tolerability 1, 4
• When directly compared to liposomal amphotericin B, shows slightly higher nephrotoxicity (OR 1.31, RR 1.24) 6
• Patients experience more chills/rigors and nephrotoxicity based on doubling of serum creatinine compared to liposomal formulations 7

4. Liposomal Amphotericin B (L-AmB) - Least Nephrotoxic

• Among all amphotericin B formulations, liposomal amphotericin B affords the greatest renal protection 1
• Significantly fewer patients develop nephrotoxic effects compared to AmB-d in double-blind randomized trials 7
• Approximately 19-50% of patients still experience some degree of renal injury, but adverse events are manageable with only 12% requiring readmission 8
• Has the lowest rate of infusion-related events among all formulations 5
• In head-to-head comparison with ABLC, patients receiving L-AmB at 3 or 5 mg/kg/day experienced less nephrotoxicity, fewer chills/rigors, and fewer toxic reactions requiring discontinuation 7

Mechanism Explaining the Difference

The key difference is that lipid formulations reduce direct exposure of renal tubular cells to free amphotericin B, while AmB-d delivers the drug directly to renal tissue. 8

• AmB-d binds directly to cholesterol in mammalian cell membranes, causing end-organ dysfunction particularly in the kidneys 8, 3
• The lipid encapsulation in L-AmB and ABLC creates a protective barrier that decreases drug delivery to renal tubular cells 8
• This explains why lipid formulations maintain antifungal efficacy while dramatically reducing nephrotoxicity 4

Clinical Implications for Formulation Selection

• When lipid formulations are available, they are strongly preferred over AmB-d 1
• L-AmB is particularly important for patients at high risk for renal failure, including those with pre-existing renal disease, hematopoietic cell transplant recipients, and patients receiving other nephrotoxic agents 1
• The three lipid formulations have different pharmacological properties and rates of adverse events and should not be interchanged without careful consideration 1
• Despite higher cost, lipid formulations reduce nephrotoxicity-related complications, hospital costs, need for hemodialysis, and mortality 7

Important Caveat

All amphotericin B formulations should be avoided for urinary tract candidiasis, as the renal protection afforded by lipid formulations theoretically reduces drug delivery to the urinary tract 1