[Acute nephrotoxicity caused by amphotericin B in the dog]

Area of Science:

• Nephrology
• Pharmacology
• Renal Physiology

Background:

• Amphotericin-B (AMB) is a critical antifungal agent for systemic infections.
• Nephrotoxicity is a significant limitation to AMB use, impacting renal blood flow and function.
• Understanding AMB's acute renal effects is crucial for patient management.

Purpose of the Study:

• To investigate the acute effects of Amphotericin-B on canine renal function.
• To assess hemodynamic changes, including intrarenal blood flow, during AMB administration.
• To differentiate effects during hydropenia versus water diuresis.

Main Methods:

• Acute administration of Amphotericin-B in dogs under hydropenic and water-diuresis conditions.
• Measurement of renal function parameters: creatinine clearance, urinary osmolality, solute excretion, and free water formation.
• Hemodynamic assessment using the microsphere method to measure intrarenal blood flow.

Main Results:

• Unilateral renal artery infusion of AMB significantly decreased creatinine clearance and urinary output in the infused kidney.
• Systemic AMB infusion during water diuresis markedly reduced creatinine clearance and free water formation.
• Reduced renal blood flow correlated with decreased creatinine clearance, but not with altered water/sodium excretion patterns.

Conclusions:

• Acute Amphotericin-B administration impairs canine renal function, evidenced by reduced creatinine clearance.
• The observed nephrotoxicity is partly attributed to a decrease in renal blood flow (ischemic action).
• Further research is needed to clarify the mechanisms behind AMB-induced alterations in water and sodium excretion.