Does amphotericin (antifungal medication) cause acidosis?

Does Amphotericin B Cause Acidosis?

Yes, amphotericin B causes renal tubular acidosis (RTA) as a well-established nephrotoxic effect, occurring in the majority of patients receiving the drug, particularly with the conventional deoxycholate formulation. 1

Mechanism of Acidosis

• Amphotericin B causes selective distal tubular epithelial toxicity, leading to renal tubular acidosis through direct damage to the renal tubules 2
• The drug binds to cholesterol in mammalian cell membranes, resulting in end-organ dysfunction, particularly affecting kidney tubular function 1, 2
• The nephrotoxicity manifests as both glomerular damage (causing azotemia) and tubular damage (causing electrolyte wasting and acidosis) 2

Clinical Manifestations

• Renal tubular acidosis occurs to varying degrees in almost all patients receiving amphotericin B deoxycholate 3
• The acidosis is accompanied by electrolyte abnormalities including hypokalemia (in up to 80% of patients), urinary potassium and magnesium wasting 1, 2, 3
• Additional manifestations include impaired urinary concentration ability, azotemia, and metabolic acidosis 1, 3, 4

Formulation-Specific Considerations

• Amphotericin B deoxycholate has the highest risk of causing renal tubular acidosis and should be reserved for resource-limited settings where alternatives are unavailable 1
• Lipid formulations (liposomal amphotericin B, amphotericin B lipid complex) have considerably less nephrotoxicity, including reduced risk of acidosis, compared to the deoxycholate formulation 1
• However, renal tubular acidosis and nephrogenic diabetes insipidus can still occur even with lipid formulations, though less commonly 5

Risk Factors for Severity

• Concomitant nephrotoxic medications (particularly cyclosporine and tacrolimus) exacerbate the acidosis and other renal toxicities 1, 2
• Higher doses of amphotericin B (>1 mg/kg) are associated with more severe electrolyte abnormalities and acidosis 2
• Pre-existing renal impairment, diabetes mellitus, and underlying renal disease increase risk 1
• Salt depletion enhances the development of nephrotoxicity and acidosis 3

Prevention and Monitoring Strategies

• Hydration with 0.9% saline intravenously 30 minutes before amphotericin B infusion can ameliorate nephrotoxicity and reduce the severity of acidosis 2, 3
• Regular monitoring of serum electrolytes (particularly potassium, magnesium, and bicarbonate) is essential during therapy 1, 2
• Monitoring should include baseline and frequent (once or twice weekly) serum chemistry values including renal function and acid-base status 2
• Volume expansion with a salt load immediately prior to dosing, and monitoring with repletion of potassium and magnesium as needed, are warranted 1

Management Approach

• Oral administration of potassium bicarbonate can help correct both the hypokalemia and metabolic acidosis 4
• Electrolyte supplementation, increased intervals between doses, or drug holidays may be required in severe cases 2
• Consider switching to lipid formulations if acidosis develops with deoxycholate formulation 1
• In severe cases with progressive acidosis, interruption of amphotericin B therapy may be necessary, with reversal of kidney lesion manifestations typically occurring after discontinuation 4

Important Caveats

• The renal tubular acidosis is usually reversible upon withdrawal of therapy, with renal function gradually returning to baseline in most patients 3, 6
• However, permanent damage can be sustained when cumulative doses exceed 5g 3
• The earliest manifestations of nephrotoxicity (including acidosis) can be observed following administration of total doses as low as 1,000 mg 4