bStudies on amphotericin B (AmB) nephrotoxicity use diverse definitions of acute kidney injury (AKI). Here, we used the new Kidney Disease Improving Global Outcome (KDIGO) system to describe the incidence, predictors, and impact of AmB-induced AKI on hospital mortality in 162 patients treated with AmB (120 with deoxycholate preparation and 42 with liposomal preparation). KDIGO stage 1 requires an absolute increase of >0.3 mg/dl or >1.5؋ over baseline serum creatinine (SCr), while stage 2 requires >2؋, and stage 3 requires >3؋. 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 >2؋ (NT2؋) increase in baseline SCr. The overall incidence of AmB-induced AKI by KDIGObin was 58.6% (stage 1, 30.9%; stage 2, 18.5%; stage 3, 9.3%). Predictors of AKI by KDIGObin were older age and use of furosemide and angiotensin-converting enzyme inhibitor (ACE-I). Traditional criteria detected lower incidences of AKI, at 45.1% (NT0.5) and 27.8% (NT2؋). Predictors of AKI by traditional criteria were older age and use of vancomycin (NT0.5) and use of vancomycin and vasopressors (NT2؋). KDIGObin detected AKI 2 days earlier than the most sensitive traditional criterion. However, only traditional criteria were associated with intensive care unit (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.A mphotericin B (AmB) is a powerful antifungal and antiparasitic agent that binds to the ergosterol component of microbial membranes, creating pores that result in cation leakage and cell death (1). AmB is the drug of choice for the treatment of severe forms of leishmaniasis and remains a lifesaving option for certain invasive fungal infections. Nevertheless, its use is limited by toxicity, including acute kidney injury (AKI).AmB administration leads to direct renal vasoconstriction and causes a profound reduction in renal blood flow (2-4). In addition, AmB alters renal tubular cell membrane permeability (5, 6), allowing back diffusion of hydrogen ions and thereby impairing acid excretion. Recent data suggest that sodium entry through membrane pores activates mitogen-activated protein (MAP) kinases and increases intracellular calcium concentration, culminating in renal tubular cell injury (7). Therefore, AmB-induced AKI appears to result from a combination of ischemic and toxic insults (8). Phenotypically, AmB-induced AKI manifests itself through elevated serum creatinine (SCr) levels that may be accompanied by renal tubular acidosis, characterized by hyperchloremic metabolic acidosis, hypokalemia, and hypomagnesemia.Mistro and coworkers (9) systematically reviewed the literature on AmB-induced AKI and...

f 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.