title: Impact of liposomal amphotericin B on renal function in critically ill patients with renal function impairment.
abstract: OBJECTIVE
  To assess the tolerability of liposomal amphotericin B (L-AmB) in critically ill patients with elevated serum creatinine concentrations (Cr) (> 1.5 mg/dL) at starting L-AmB therapy.
  
  
  METHODS
  Retrospective, multicenter, comparative study of two cohorts of critically ill patients treated with L-AmB during 3 or more days, the difference between them was the level of Cr at the beginning of treatment. A cutoff value of Cr of 1.5 mg/dL was established. Patients undergoing extrarenal depuration procedures before or 48 hours after starting L-AmB were excluded. The primary endpoint was the difference between Cr values at the end of treatment as compared with Cr at starting L-AmB. Secondary endpoints were treatment-related withdrawals, need of extrarenal depuration techniques, and treatment-related severe adverse events. Demographic data, underlying illness, indication of L-AmB therapy, concomitant risk factors of nephrotoxicity, and vital status at ICU and hospital discharge were recorded.
  
  
  RESULTS
  A total of 122 patients admitted to 26 ICUs (16 with Cr > 1.5 g/dL; 106 with normal Cr levels) were recruited. Main reasons for the use of L-AmB in both groups were the broad spectrum of the drug and the presence of hemodynamic instability. L-AmB was administered as first-line treatment in 68.8% of patients with elevated Cr and in 52.8% with normal Cr. The APACHE II score on ICU admission was 25 in patients with elevated Cr and 17 in those with normal Cr values (p < 0.001). Duration of treatment with L-AmB was 16 and 12 days in patients with elevate and normal Cr values, respectively, with a mean dose of 3.5 vs 3.9 mg/kg/day. The use of concomitant nephrotoxic drugs, mortality rate, and ICU and hospital length of stay were similar in both cohorts. In patients with renal function impairment at the initiation of L-AmB treatment, an absolute decrease of Cf-Ci of 1.08 mg/dL was observed (P < 0.001). A decrease of Cr levels to normal limits was observed in 50% of the patients; in 37.5% of patients there was a decrease but normal levels were not achieved, whereas a Cr increased occurred in only one (6.25%) patient. None of the patients required withdrawal of L-AmB or use of extrarenal depuration procedures. Treatment-related severe adverse events were not reported.
  
  
  CONCLUSIONS
  In critically ill patients with impaired renal function, the impact of L-AmB on renal function was minimal. L-AmB can be used for the treatment of fungal infections in critically ill patients independently of renal function at the initiation of treatment.
authors.affiliation: Servicio de Medicina Intensiva, Parc de Salut Mar, Barcelona, Spain. Falvarez@parcdesalutmar.cat
authors.forename: F
authors.initials: F
authors.lastname: Alvarez-Lerma
authors.forename: M C
authors.initials: MC
authors.lastname: Soriano
authors.forename: M
authors.initials: M
authors.lastname: Rodríguez
authors.forename: M
authors.initials: M
authors.lastname: Catalán
authors.forename: A M
authors.initials: AM
authors.lastname: Llorente
authors.forename: N
authors.initials: N
authors.lastname: Vidart
authors.forename: M
authors.initials: M
authors.lastname: Garitacelaya
authors.forename: E
authors.initials: E
authors.lastname: Maraví
authors.forename: E
authors.initials: E
authors.lastname: Fernández
authors.forename: F
authors.initials: F
authors.lastname: Alvarado
authors.forename: M
authors.initials: M
authors.lastname: López
authors.forename: B
authors.initials: B
authors.lastname: Alvarez-Sánchez
authors.forename: J
authors.initials: J
authors.lastname: Espinosa
authors.forename: E
authors.initials: E
authors.lastname: Quintana
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000666:Amphotericin B / Q000009:adverse effects* / Q000627:therapeutic use; D000935:Antifungal Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D016638:Critical Illness / Q000628:therapy*; D005260:Female; D006801:Humans; D007223:Infant; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000150:complications*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000150:complications / Q000188:drug therapy; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B; D003404:Creatinine