Prevention of Renal Stones in Patients Treated with Amphotericin B
Amphotericin B does not cause renal stones—it causes nephrotoxicity through tubular damage, hypokalemia, and renal tubular acidosis, but stone formation is not a recognized complication of amphotericin therapy. 1
Understanding Amphotericin B Nephrotoxicity
The renal complications of amphotericin B are well-characterized but do not include nephrolithiasis:
- Tubular damage occurs in up to 80% of patients, manifesting as hypokalemia, hypomagnesemia, renal tubular acidosis, and urinary potassium wasting 2, 3, 1
- Glomerular dysfunction presents as azotemia and elevated serum creatinine 2, 3
- Nephrocalcinosis (calcium deposition in renal tissue) can occur, particularly with large cumulative doses (>5g), but this is tissue calcification, not stone formation 1
Prevention of Amphotericin B Nephrotoxicity
While stones are not the concern, preventing nephrotoxicity is critical:
Hydration and Sodium Loading
- Administer 0.9% saline (1 liter or 1000-1500 mL/m² body surface) intravenously 30 minutes before each amphotericin B infusion to reduce nephrotoxicity 3, 4, 5
- Target urine output of ≥4000 mL/day with vigorous hydration to prevent renal damage 4
- Oral rehydration solution (3 liters daily) is as effective as intravenous saline for preventing glomerular damage and superior for preventing hypokalemia 6
- Sodium supplementation through either IV saline or concurrent ticarcillin significantly reduces nephrotoxicity development (P<0.01) 7
Electrolyte Monitoring and Replacement
- Monitor serum potassium, magnesium, calcium, and bicarbonate at baseline, then at 1,2, and 4 weeks, and every 3 months during therapy 2, 3
- Aggressively replace potassium losses (often requiring 7.45% potassium solution via central line) to prevent cardiac dysfunction 4
- Supplement magnesium as needed, as hypomagnesemia commonly accompanies hypokalemia 1
- Supplemental alkali medication may decrease renal tubular acidosis complications 1
Formulation Selection
- Lipid formulations (liposomal amphotericin B at 3-5 mg/kg/day or amphotericin B lipid complex at 5 mg/kg/day) are considerably less nephrotoxic than conventional amphotericin B deoxycholate 2, 8
- Liposomal amphotericin B demonstrated significantly fewer patients with nephrotoxicity (doubling of serum creatinine) and hypokalemia compared to conventional formulations 8
- Reserve amphotericin B deoxycholate (0.7-1.0 mg/kg/day) only for patients at low risk for nephrotoxicity 2
- Switch to lipid formulations if serum creatinine rises above 2.5 mg/dL on conventional amphotericin B 2
Renal Function Monitoring
- Monitor serum creatinine and creatinine clearance frequently during therapy 2, 1
- Increase hydration when serum creatinine shows a 20% increase from baseline 5
- In patients with pre-existing renal dysfunction, lipid formulations should be used from the outset 2
Avoiding Concomitant Nephrotoxins
- Avoid concurrent use of aminoglycosides, cyclosporine, pentamidine, cidofovir, and foscarnet when possible 2, 1
- If combination nephrotoxic therapy is unavoidable, use lipid formulations and intensify monitoring 2, 1
Common Pitfall
The term "amphotericin renal stones" likely represents confusion with nephrocalcinosis (tissue calcification) rather than true nephrolithiasis. Nephrocalcinosis occurs with prolonged high-dose therapy but does not require stone-prevention strategies like increased fluid intake for calcium oxalate stones—it requires the nephrotoxicity prevention measures outlined above 1.