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dc.contributor.advisorGlesby, Marshall
dc.contributor.authorRocha, Paulo
dc.date.accessioned2019-03-26T15:29:15Z
dc.date.available2019-03-27T06:01:17Z
dc.date.issued2015
dc.identifier.urihttps://hdl.handle.net/1813/64643
dc.description.abstractMANUSCRIPT 1: INCIDENCE, PREDICTORS AND IMPACT OF AMPHOTERICIN B NEPHROTOXICITY ON HOSPITAL MORTALITY USING NEWER ACUTE KIDNEY INJURY DIAGNOSTIC CRITERIA: Studies on amphotericin B (AmB) nephrotoxicity use diverse definitions of acute kidney injury (AKI). Herein, we used the new KDIGO system to describe the incidence, predictors and impact of AmB-induced AKI on hospital mortality in 162 patients treated with AmB (120 deoxycholate and 42 liposomal). KDIGO stage 1 requires an absolute increase ? 0.3 mg/dl or ? 1.5x over baseline serum creatinine (SCr); stage 2 ? 2x, and stage 3 ? 3x. A binary KDIGO definition (KDIGObin) corresponds to stage ? 1. For comparison, we included two definitions of AKI traditionally utilized in nephrotoxicity studies: ? 0.5 mg/dl (NT0.5) and ? 2x (NT2x) increase in baseline SCr. The overall incidence of AmB-induced AKI by KDIGObin was 58.6% (staged as: 1 = 30.9%; 2 = 18.5% and, 3 = 9.3%). Predictors of AKI by KDIGObin were older age and use of furosemide and ACE-I. Traditional criteria detected lower incidences of AKI: 45.1% (NT0.5) and 27.8% (NT2x). Predictors of AKI by traditional criteria were older age and use of vancomycin (NT0.5) and use of vancomycin and vasopressors (NT2x). KDIGObin detected AKI 2 days earlier than the most sensitive traditional criteria. However, only traditional criteria were associated with ICU admission, mechanical ventilation and mortality. In conclusion, the increase in sensitivity of KDIGObin is accompanied by a loss of specificity and ability to predict outcomes. Prospective studies are required to weigh the potential gain from early AKI detection against the potential loss from undue changes in management in patients with subtle elevations in SCr. MANUSCRIPT 2: ROLE OF URINE NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (NGAL) IN THE EARLY DIAGNOSIS OF AMPHOTERICIN B-INDUCED ACUTE KIDNEY INJURY: 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 ?1.5 times 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.
dc.language.isoen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAcute kidney injury
dc.subjectAmphotericin B
dc.subjectBiological markers
dc.subjectEndemic mycoses
dc.subjectLeishmania
dc.subjectNGAL
dc.titleClinical Epidemiology And Diagnosis Of Amphotericin B-Induced Acute Kidney Injury
dc.typedissertation or thesis
thesis.degree.disciplineClinical Epidemiology & Health Services Research
thesis.degree.grantorWeill Cornell Graduate School of Medical Sciences
thesis.degree.levelMaster of Science


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