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Role of Urine Neutrophil Gelatinase-Associated Lipocalin (NGAL) in the Early Diagnosis of Amphotericin B-induced Acute Kidney Injury.
Antimicrob Agents Chemother. 2015 Aug 24;
Authors: Rocha PN, Macedo MN, Kobayashi CD, Moreno L, Guimarães LH, Machado PR, Badaró R, Carvalho EM, Glesby MJ
Abstract
Neutrophil Gelatinase-Associated Lipocalin (NGAL) detects acute kidney injury (AKI) earlier than serum creatinine (SCr) 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 SCr and UrNGAL at baseline and daily after initiation of AmB up to day 14 or development of AKI by SCr criteria. AKI was defined according to Kidney Diseases Improving Global Outcomes (KDIGO) criteria (increase in SCr by ≥ 0.3 mg/dl within 48 hours or ≥1.5x baseline within 7 days). We studied 24 patients with a mean age of 48.4 ± 16.4 years. Most were male and received AmB (12 deoxycholate and 12 liposomal) for the treatment of leishmaniasis (91.7%). Overall, 17/24 patients fullfilled KDIGO criteria for AKI. Peak UrNGAL levels were higher in AKI than in No AKI patients and in recipients of deoxycholate than liposomal AmB. The diagnostic performance of UrNGAL on day 5 to detect AKI was moderate, with an AUC 0.68 (95% CI 0.41 to 0.95). In the deoxycholate subgroup, however, the AUC rose to 0.89 (95% CI 0.67 to 1.00). In a patient-level analysis, we found that UrNGAL was able to detect AKI 3.2 days earlier than SCr (3.7 ± 2.5 versus 6.9 ± 3.3 days, time to AKI by UrNGAL and SCr criteria, respectively; p = 0.001). Future studies should evaluate if a UrNGAL-oriented treatment strategy will improve outcomes. These findings with 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.
PMID: 26303800 [PubMed - as supplied by publisher]