How does Amphotericin B (Ampho B) affect kidney function?

Amphotericin B's Effects on Kidney Function

Amphotericin B causes significant nephrotoxicity in up to 80% of treated patients, manifesting as hypokalemia, renal tubular acidosis, decreased renal function, and electrolyte abnormalities. 1, 2

Mechanisms of Nephrotoxicity

• Amphotericin B binds to ergosterol in fungal cell membranes, but also binds to cholesterol in mammalian cell membranes, leading to end-organ dysfunction, particularly in the kidneys 2
• It causes selective distal tubular epithelial toxicity, resulting in potassium wasting through the distal tubules 2
• Nephrotoxicity manifests as both glomerular damage (causing azotemia) and tubular damage (causing hypokalemia and electrolyte imbalances) 1, 2
• The drug induces renal vasoconstriction, further compromising kidney function 3, 4

Clinical Manifestations

• Hypokalemia occurs in up to 80% of patients receiving conventional amphotericin B treatment 1, 2
• Bicarbonaturia and renal tubular acidosis are common manifestations 1
• Decreases in renal erythropoietin production leading to anemia 1
• Elevations in serum creatinine levels, often exceeding 2.5 mg/dL 1, 5
• Acute renal failure occurs in approximately 31% of patients, defined as an increase of more than 50% of baseline creatinine 6

Risk Factors for Nephrotoxicity

• Higher daily doses of amphotericin B (>35 mg/day) significantly increase risk 5
• Male sex and weight ≥90 kg are associated with greater nephrotoxicity 5
• Pre-existing chronic renal disease 7, 5
• Concomitant use of other nephrotoxic medications (aminoglycosides, cyclosporine, pentamidine) 7, 5
• Volume depletion and salt depletion enhance nephrotoxicity 4

Prevention and Management Strategies

• Lipid formulations of amphotericin B (liposomal amphotericin B, amphotericin B lipid complex) are less nephrotoxic than conventional amphotericin B deoxycholate and should be preferred, especially in high-risk patients 1
• Intravenous hydration with 0.9% saline before and after amphotericin B administration significantly reduces nephrotoxicity 7, 6, 4
• Supplemental alkali medication may decrease renal tubular acidosis complications 7
• Regular monitoring of renal function, serum electrolytes (particularly potassium and magnesium), and other laboratory parameters is essential 7
• Slower infusion rates (over 2-6 hours) may reduce nephrotoxicity 2, 7

Monitoring Recommendations

• Baseline and frequent (1-2 times weekly) monitoring of:
  • Serum creatinine and BUN 7
  • Serum electrolytes, particularly potassium and magnesium 2, 7
  • Complete blood count and hemoglobin 7
  • Liver function tests 7

Reversibility of Nephrotoxicity

• In most patients, renal function gradually returns to baseline after discontinuation of therapy 6, 4
• However, permanent damage may occur, especially when cumulative doses exceed 5g 4
• At discharge, approximately 70% of patients with moderate-to-severe nephrotoxicity still have serum creatinine levels ≥0.5 mg/dL above baseline 5

Special Considerations

• In low-risk patients receiving proper sodium chloride loading, amphotericin B-induced nephrotoxicity is typically small and reversible 6
• Hemodialysis is rarely required (approximately 0.6% of cases) despite nephrotoxicity 5
• For patients requiring both amphotericin B and other nephrotoxic medications, intensive monitoring of renal function is essential 7