title: Role of urine neutrophil gelatinase-associated lipocalin in the early diagnosis of amphotericin B-induced acute kidney injury.
abstract: Determination of the neutrophil gelatinase-associated lipocalin (NGAL) level can be used to detect acute kidney injury (AKI) earlier than determination of the serum creatinine (SCr) level in settings such as cardiac surgery, contrast nephropathy, and intensive care units. We hypothesized that urine NGAL (UrNGAL) would be an early biomarker of drug nephrotoxicity. To test this, we studied hemodynamically stable patients treated with amphotericin B (AmB). We measured the SCr and UrNGAL levels at the baseline and daily after initiation of AmB up to day 14 or development of AKI by the use of the SCr criterion. AKI was defined according to a Kidney Disease: Improving Global Outcomes (KDIGO) criterion (an increase in the SCr level by ≥0.3 mg/dl within 48 h or an SCr level ≥1.5 times the baseline level within 7 days). We studied 24 patients with a mean age of 48.4 ± 16.4 years. Most patients were male, and the patients received AmB (12 received AmB deoxycholate and 12 received liposomal AmB) for the treatment of leishmaniasis (91.7%). Overall, 17/24 patients fulfilled a KDIGO criterion for AKI. Peak UrNGAL levels were higher in patients with AKI than in patients without AKI and in recipients of AmB deoxycholate than in recipients of liposomal AmB. The diagnostic performance of the UrNGAL level on day 5 for the detection of AKI was moderate, with the area under the curve (AUC) being 0.68 (95% confidence interval [CI], 0.41 to 0.95). In the subgroup receiving AmB deoxycholate, however, the AUC rose to 0.89 (95% CI, 0.67 to 1.00). In a patient-level analysis, we found that AKI could be detected 3.2 days earlier by the use of the UrNGAL criterion than by the use of the SCr criterion (times to AKI by the UrNGAL and SCr criteria, 3.7 ± 2.5 versus 6.9 ± 3.3 days, respectively; P = 0.001). Future studies should evaluate if a treatment strategy oriented toward evaluation of UrNGAL levels will improve outcomes. These findings for AmB-induced AKI in leishmaniasis patients could serve as a basis for the investigation of urine biomarkers in the early detection of drug nephrotoxicity in other clinical settings.
authors: Department of Medicine and Diagnostic Support, Medical School of Bahia, Federal University of Bahia, Salvador, Bahia, Brazil paulonrocha@ufba.br.
authors: Paulo Novis
authors: PN
authors: Rocha
authors: Immunology Service, Hospital Universitário Professor Edgard Santos, Federal University of Bahia, Salvador, Bahia, Brazil.
authors: Michael Nascimento
authors: MN
authors: Macedo
authors: Department of Medicine and Diagnostic Support, Medical School of Bahia, Federal University of Bahia, Salvador, Bahia, Brazil.
authors: Carla Dinamérica
authors: CD
authors: Kobayashi
authors: Division of Infectious Diseases, Hospital Universitário Professor Edgard Santos, Salvador, Bahia, Brazil.
authors: Lis
authors: L
authors: Moreno
authors: Immunology Service, Hospital Universitário Professor Edgard Santos, Federal University of Bahia, Salvador, Bahia, Brazil National Institute of Science and Technology in Tropical Diseases (INCT-DT), Salvador, Bahia, Brazil.
authors: Luiz Henrique Santos
authors: LH
authors: Guimarães
authors: Immunology Service, Hospital Universitário Professor Edgard Santos, Federal University of Bahia, Salvador, Bahia, Brazil National Institute of Science and Technology in Tropical Diseases (INCT-DT), Salvador, Bahia, Brazil.
authors: Paulo Roberto Lima
authors: PR
authors: Machado
authors: Department of Medicine and Diagnostic Support, Medical School of Bahia, Federal University of Bahia, Salvador, Bahia, Brazil Division of Infectious Diseases, Hospital Universitário Professor Edgard Santos, Salvador, Bahia, Brazil.
authors: Roberto
authors: R
authors: Badaró
authors: Department of Medicine and Diagnostic Support, Medical School of Bahia, Federal University of Bahia, Salvador, Bahia, Brazil Immunology Service, Hospital Universitário Professor Edgard Santos, Federal University of Bahia, Salvador, Bahia, Brazil Centro de Pesquisas Gonçalo Moniz (Fiocruz-Ba), Salvador, Bahia, Brazil National Institute of Science and Technology in Tropical Diseases (INCT-DT), Salvador, Bahia, Brazil.
authors: Edgar M
authors: EM
authors: Carvalho
authors: Department of Medicine, Weill Cornell Medical College, New York, New York, USA.
authors: Marshall Jay
authors: MJ
authors: Glesby
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis*; D000328:Adult; D000666:Amphotericin B / Q000009:adverse effects* / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D003840:Deoxycholic Acid / Q000009:adverse effects / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007896:Leishmaniasis / Q000188:drug therapy; D054834:Lipocalins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D004338:Drug Combinations; D054834:Lipocalins; C068538:liposomal amphotericin B; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination; D003404:Creatinine