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[Acute nephrotoxicity caused by amphotericin B in the dog]
J L Monteiro1, A C Seguro, A dos S Rocha
1Laboratório de Pesquisa Básica da Disciplina de Nefrologia, Faculadade de Medicina, Universidade de São Paulo.
Abstract:
Amphotericin-B is the drug of choice for the treatment of serious systemic fungal infections. The major limitation for the use of this drug is its potential nephrotoxicity. The chronic and acute administration causes both a reduction of renal blood flow and glomerular filtration rate, determining a fall of renal concentrating ability. Our study was designed to determine the acute effects of Amphotericin-B on dogs renal function, during hydropenia and water diuresis. In addition a hemodynamic study, with the measurement of intrarenal blood flow by the microsphere method was performed. The hydropenic dogs received the drug directly into the left renal artery. There was a significant decrease in creatinine clearance, urinary osmolality, and urinary solute excretion, in the left kidney only. Amphotericin-B was infused into the aorta above the renal arteries in the group in which the water diuresis was induced. This acute infusion produced intense fall in creatinine clearance and in the free water formation, as well as in absolute excretion of sodium. The hemodynamic study showed that the reduction of creatinine clearance may be due to the decrease in renal blood flow, and the alterations in the urinary excretion of water and sodium could not be correlated with the distribution of cortical blood flow to the deep nephrons. These findings suggest that the effects of Amphotericin-B may be attributed, at least in part, to its ischemic action.
Insights
Amphotericin-B (AMB) causes acute kidney injury by reducing renal blood flow and impairing kidney function. This study in dogs suggests AMB
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.