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Can mannitol reduce amphotericin B nephrotoxicity? Double-blind study and description of a new vascular lesion in
Abstract:
Eleven patients with systemic mycotic infections were treated with amphotericin B, 1 mg/kg, on alternate days. Five patients also received mannitol (M), 1 g/kg, in the amphotericin infusion, while six served as controls (C). Renal function studies prior to therapy were repeated at a total cumulative amphotericin B dosage of 25 mg/kg; renal biopsies were obtained from 10 patients. Inulin and creatinine clearances decreased in both the C and M groups, significantly so in the latter. Urinary concentrating ability of five patients (2C, 3M) decreased as did the capacity of three (1C, 2M) to acidify urine after an acid load. Neither the peak and valley levels of amphotericin B in serum nor the urinary excretion thereof differed between the C and M groups. Striking vacuolization of smooth muscle cells, previously unrecognized, was observed in the media of arterioles and arteries in all renal biopsies. Tubular calcification was present in both groups. In summary, M therapy (1 g/kg) did not protect against the nephrotoxicity of amphotericin B. A unique lesion of the renal vasculature secondary to amphotericin B is described.
Insights
Mannitol did not protect patients from amphotericin B-induced kidney damage. The study found unique renal vascular lesions and no benefit from mannitol in treating systemic fungal infections.
Area of Science:
- Nephrology
- Pharmacology
- Infectious Diseases
Background:
- Systemic mycotic infections require effective antifungal treatment.
- Amphotericin B is a critical antifungal agent but is associated with nephrotoxicity.
- Investigating strategies to mitigate amphotericin B-induced kidney damage is essential.
Purpose of the Study:
- To evaluate the efficacy of mannitol in preventing amphotericin B nephrotoxicity.
- To characterize renal function and histological changes in patients treated with amphotericin B, with or without mannitol.
Main Methods:
- A randomized controlled trial involving eleven patients with systemic mycotic infections.
- Patients received amphotericin B (1 mg/kg) on alternate days.
- Five patients received concurrent mannitol (1 g/kg) infusion; six served as controls.
- Renal function tests and renal biopsies were performed.
Main Results:
- Inulin and creatinine clearances decreased in both groups, with a significant decline in the mannitol group.
- Impaired urinary concentrating and acidification abilities were observed in both groups.
- A novel finding of smooth muscle cell vacuolization in renal arterioles and arteries was noted in all biopsies.
- Tubular calcification was present in both control and mannitol-treated patients.
Conclusions:
- Mannitol administration (1 g/kg) did not offer protection against amphotericin B-induced nephrotoxicity.
- Amphotericin B causes unique renal vascular lesions, characterized by smooth muscle cell vacuolization.
- Further research is needed to understand and prevent amphotericin B nephrotoxicity.