1 Medical Intensive Care Unit and 2 Department of Haematology, Charles Nicolle University Hospital, Rouen 76031, France
Keywords: amphotericin B, nephrotoxicity, antifungal therapy
Sir,
Invasive fungal infections are a major cause of morbidity and mortality in neutropenic patients. The diagnosis is often difficult, thus patients with persistent fever and neutropenia frequently receive empirical antifungal therapy. Unfortunately, empirical treatment with amphotericin B may be limited by dose-dependent nephrotoxicity.1 The lipid formulations of amphotericin B, such as liposomal amphotericin B (Ambisome) and amphotericin B in a lipid complex (ABLC; Abelcet) have been developed in attempts to improve tolerability.1
We report a case of amphotericin B-related renal toxicity suspected to be sustained after switch to liposomal amphotericin B. A 30-year-old man with acute monoblastic leukaemia (AML5) was referred to the haematology department in August 2000. AML5 relapse was diagnosed in December 2001 requiring a new chemotherapy. Empirical antimicrobial therapy combining cefepime (2 g), netilmicin (5 mg/kg) and amphotericin B (1 mg/kg) was initiated due to persistent fever with severe watery diarrhoea. Despite rehydration, the patient became confused. He was transferred to our medical Intensive Care Unit (ICU) for coma and severe metabolic disorders. On admission, clinical examination showed coma (Glasgow Coma Score 7), fever (40°C), tachypnoea (35 breaths/min) and tachycardia (150 beats/min) with normal systolic arterial blood pressure (100 mmHg). There was no evidence of extracellular dehydration. A computerized tomographic cerebral scan and electroencephalogram were normal. Baseline biological data found severe neutropenia, acute renal failure, metabolic acidosis (pHa 7.25; base excess 15.1 mmol/L; CO2 arterial pressure 37 mmHg) and normal anion gap (12 mequiv./L). We observed hypernatraemia (166 mmol/L) and hypokalaemia (3.4 mmol/L). Diuresis sharply increased (5000 mL/day) with low natriuresis (6 mmol/24 h) and increased kaliuresis (64 mmol/24 h). Plasma and urine osmolality was altered (358 and 434 mosm/L, respectively). The clinical presentation was attributed to metabolic disorders with high variations in natraemia before ICU admission (135166 mmol/L on two consecutive days). This disorder could be dependent on diarrhoeic enteritis, fever and insufficient hydration, and aggravated by amphotericin B. The renal toxicity consisted of mild acute renal failure, nephrogenic diabetes insipidus documented by high serum anti-diuretic hormone (ADH) level (17.9 ng/L), polyuria, negative desmopressin test and type 1 renal tubular acidosis (urinary pH > 5.5 with base excess <15 mmol/L, normal anion gap, hypokalaemia 3.4 mmol/L). We stopped amphotericin B for liposomal amphotericin B (3 mg/kg). Nephrogenic diabetes insipidus and distal tubulopathy persisted despite the switch to liposomal amphotericin B (Figure 1). We therefore stopped liposomal amphotericin B administration 1 week later. Five days following liposomal amphotericin B discontinuation an improvement in renal function, metabolic acidosis and kalaemia was observed. The serum ADH level then rapidly decreased and polyuria resolved with concomitant normalization of natraemia (Figure 1). The patient was referred to the haematology department with no neurological sequelae.
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Acknowledgements
We thank Richard Medeiros for his valuable advice in editing the manuscript.
Footnotes
* Corresponding author. Tel: +33-232-888-261; Fax: +33-232-888-314; E-mail: Fabienne.Tamion{at}chu-rouen.fr
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