What to do for Acute Kidney Injury (AKI) after injection of liposomal amphotericin B?

Management of Acute Kidney Injury After Liposomal Amphotericin B

When AKI develops during liposomal amphotericin B therapy, immediately discontinue diuretics, initiate aggressive sodium loading with 0.9% saline (≥10 mL/kg/day for 7 consecutive days), supplement potassium and magnesium, and eliminate all concomitant nephrotoxic medications while continuing the antifungal if the invasive fungal infection remains life-threatening. 1, 2

Immediate Interventions

Fluid Management (Most Critical)

• Administer ≥10 mL/kg/day of 0.9% saline for 7 consecutive days from AKI onset, as this significantly increases recovery rates from stage 1 AKI (91% vs 50% without adequate fluids, p=0.017) 2
• Daily fluid volume positively correlates with AKI recovery across all stages (p=0.043) 2
• Provide 0.9% saline infusion 30 minutes before each amphotericin B dose to reduce nephrotoxicity risk 1, 3

Electrolyte Repletion

• Aggressively supplement potassium and magnesium, as amphotericin B causes tubular damage leading to electrolyte wasting 1, 4
• Monitor serum potassium and magnesium at least twice weekly, as hypokalemia potentiates cardiac dysfunction and digitalis toxicity 1, 4
• Serum potassium <3.5 mEq/L before therapy is specifically associated with severe AKI (stages 2-3) 5

Eliminate Nephrotoxic Exposures

• Immediately discontinue all diuretics before each amphotericin B dose 1
• Stop concomitant nephrotoxic medications including aminoglycosides, vancomycin, cyclosporine, pentamidine, and NSAIDs 1, 4
• Each additional nephrotoxin increases AKI odds by 53%, and multiple nephrotoxins more than double the risk 6

Risk Factors Requiring Heightened Vigilance

High-Risk Medication Combinations

• Prior treatment with ACE inhibitors/ARBs or carbapenems increases AKI rates 5, 1
• Concomitant catecholamines or immunosuppressants significantly elevate AKI likelihood 5
• Avoid the "triple whammy" combination of NSAIDs, diuretics, and ACE inhibitors/ARBs perioperatively 6

Dosing Considerations

• Liposomal amphotericin B doses ≥3.52 mg/kg/day are independently associated with AKI development 5
• High doses were identified as a risk factor for nephrotoxicity in outpatient studies 3
• Despite this, 19-50% of patients still develop some degree of renal injury even with liposomal preparations 1

Monitoring Requirements

Frequency and Parameters

• Monitor serum creatinine and electrolytes at minimum once or twice weekly 1, 4
• Check magnesium and potassium levels regularly due to tubular wasting 1
• Assess renal function frequently, as nephrotoxicity occurs through direct tubular damage and renal vasoconstriction 1

AKI Staging and Prognosis

• AKI occurs in approximately 26-37% of patients receiving liposomal amphotericin B 5, 7
• Distribution: Stage 1 (20%), Stage 2 (11%), Stage 3 (7%) 5
• Complete renal recovery occurs in approximately 32-51% of patients after mean 9.8 ± 7.8 days 8

Decision to Continue or Discontinue Antifungal

When to Continue Despite AKI

• If the invasive fungal infection is life-threatening and no equally effective alternative exists, continue liposomal amphotericin B while implementing all protective measures 9
• Liposomal amphotericin B was successfully used in critically ill patients with AKI when treating Aspergillus, mucormycosis, and Fusarium infections 9
• The lipid formulation reduces direct exposure of renal tubular cells to free amphotericin B, explaining the improved safety profile 1

When to Consider Alternatives

• Switch to azole antifungals and/or echinocandins when equal therapeutic efficacy can be assumed (KDIGO Grade 1A recommendation) 1
• Conventional amphotericin B deoxycholate causes nephrotoxicity in the majority of patients and should be avoided 1
• Consider fluconazole for empirical therapy at institutions where mold infections and drug-resistant Candida species are uncommon 3

Critical Caveats

Dialysis Considerations

• Dialysis does not remove amphotericin B, and neither hemodialysis nor hemofiltration significantly reduces serum concentrations 1, 4
• Dose adjustment for renal replacement therapy is not required 1
• Amphotericin B is not hemodialyzable 4

Infusion-Related Precautions

• Administer lipid formulations over at least 2 hours to prevent hypotension and arrhythmias 1, 4
• Rapid intravenous infusion has been associated with hypotension, hypokalemia, arrhythmias, and shock 4
• If therapy is interrupted for >7 days, resume with the lowest dosage (0.25 mg/kg) and increase gradually 4

Multifactorial Nature of AKI

• Recent machine learning analysis identified norepinephrine, SOFA score, furosemide, C-reactive protein, and procalcitonin as important contributing factors to AKI development beyond liposomal amphotericin B administration 7
• No statistical relationship exists between liposomal amphotericin B dose at time of AKI or cumulative exposure and likelihood of renal recovery 8
• The development of AKI is multifactorial, and liposomal amphotericin B administration appears safe when protective measures are implemented 7