title: Infrequent occurrence of amphotericin B lipid complex-associated nephrotoxicity in various clinical settings at a university hospital: a retrospective study.
abstract: BACKGROUND
  Lipid-based formulations of amphotericin B (AMB) have been shown to significantly lessen the occurrence of nephrotoxicity associated with the conventional form of AMB. A MEDLINE search of literature published from 1983 to 2002, using the search terms amphotericin B and nephrotoxicity, identified only 1 large, randomized, prospective trial that has tried to compare the nephrotoxicity rates among lipid-based AMB formulations. Using the nephrotoxicity surrogate marker of doubling of serum creatinine (SCr) level, the investigators reported a high rate of AMB lipid complex (ABLC)-associated nephrotoxicity (42.3%). However, enrollment in that study was limited to only febrile neutropenic patients.
  
  
  OBJECTIVE
  This retrospective study estimated the rate of ABLC-associated nephrotoxicity in various clinical settings at a university hospital and compared that rate with previously reported rates of nephrotoxicity.
  
  
  METHODS
  Data from adult neutropenic and nonneutropenic patients receiving ABLC were collected and the degree of nephrotoxicity was determined using 2 definitions: (1) doubling of baseline SCr level using the peak value within the first 7 days, and (2) end-of-therapy doubling of baseline SCr level using the end-of-therapy value.
  
  
  RESULTS
  Data from 33 patients (20 men, 13 women; mean age, 48.6 years) were collected. Using these definitions of ABLC-associated nephrotoxicity, only 2 cases (6.1%) were observed. This rate was significantly below the 42.3% rate reported in the only large published study (95% CI, 1.7-19.6; P < 0.001). The median change in SCr level was 0.1 mg/dL (range, -1.1 to 4.3 mg/dL). Rates of change were higher in patients who died during hospitalization, but the difference was not significant. Use of concomitant nephrotoxic agents did not account for significant changes in SCr level.
  
  
  CONCLUSIONS
  Data from this study suggest that ABLC infrequently causes clinically significant nephrotoxicity. Therefore, when formulary decisions are made in the selection of a drug for use in various clinical settings, earlier data derived from a single study in febrile neutropenic patients that suggested a significantly higher rate of nephrotoxicity should be interpreted cautiously. Larger trials with more diverse patient populations are needed to better characterize institutional rates of ABLC-associated nephrotoxicity and to aid formulary decision makers.
authors.affiliation: School of Pharmacy, School of Medicine, West Virginia University, Morgantown 26506-9520, USA. dslain@hsc.wvu.edu
authors.forename: Douglas
authors.initials: D
authors.lastname: Slain
authors.forename: Karla
authors.initials: K
authors.lastname: Miller
authors.forename: Rashida
authors.initials: R
authors.lastname: Khakoo
authors.forename: Melanie
authors.initials: M
authors.lastname: Fisher
authors.forename: Trista
authors.initials: T
authors.lastname: Wierman
authors.forename: Ken
authors.initials: K
authors.lastname: Jozefczyk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D010715:Phosphatidylglycerols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies
chemical_list: D000935:Antifungal Agents; D004338:Drug Combinations; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D000666:Amphotericin B