Applying New Diagnostic Criteria for Acute Kidney Injury To Facilitate Early Identification of Nephrotoxicity in Vancomycin-Treated Patients

e To date, no comparative clinical studies have investigated the effects of different vancomycin products on nephrotoxicity. The objective of this single-center, retrospective, matched-cohort study was to investigate the impact of two different vancomycin products on the development of nephrotoxicity. The study population included adults receiving a single vancomycin product, from either Pfizer or Hospira, for their entire course of therapy. Patients were matched based on underlying nephrotoxicity risk factors. Secondary outcomes included the need for renal replacement therapy, length of hospital stay, and in-hospital mortality. One-hundred forty-six matched pairs (n ‫؍‬ 292) were included, and they had no significant differences in demographics, comorbid conditions, severity of illness, or vancomycin-associated nephrotoxicity risk factors. The frequency of nephrotoxicity was 8.9% in the Pfizer group and 11.0% in the Hospira group as defined by the 2009 consensus vancomycin guidelines (P ‫؍‬ 0.56), 17.1% in the Pfizer group and 13.0% in the Hospira group as defined by the Acute Kidney Injury Network (AKIN) (P ‫؍‬ 0.33), and 10.3% in the Pfizer group and 11.6% in the Hospira group as defined by RIFLE (risk, injury, failure, loss, and end-stage renal disease) criteria (P ‫؍‬ 0.71). There were no differences between groups in regard to nephrotoxicity by any definition or in secondary outcomes. In multivariate analysis of overall nephrotoxicity risk factors, the type of vancomycin product was not independently associated with increased odds of developing nephrotoxicity according to the RIFLE criteria. Based on our results, there are no discernible differences between Pfizer and Hospira vancomycin products in the frequency of nephrotoxicity. Confirmation of these results with other types of vancomycin and different patient populations is warranted.

Section: Discussioncontrasting

confidence: 34%

Nephrotoxicity Comparison of Two Commercially Available Generic Vancomycin Products

Sutton

Mynatt

Kaye

et al. 2015

“…Of these, 14 studies were conducted with adults and 1 involved children (38) ( Table 1). The average trough value over the duration of therapy was examined in 6 studies (13,30,38,39,43,50), and the initial trough value was considered in 8 studies (8, 15, 21-23, 32, 36, 51). Although timing differed between studies, most initial trough levels were obtained at the time or shortly after steady state was achieved (i.e., after the 3rd dose) but not greater than 4 days into therapy (Table 2).…”

Section: Resultsmentioning

confidence: 99%

Systematic Review and Meta-Analysis of Vancomycin-Induced Nephrotoxicity Associated with Dosing Schedules That Maintain Troughs between 15 and 20 Milligrams per Liter

Hal

Paterson

Lodise

2013

520

402

dIn an effort to maximize outcomes, recent expert guidelines recommend more-intensive vancomycin dosing schedules to maintain vancomycin troughs between 15 and 20 mg/liter. The widespread use of these more-intensive regimens has been associated with an increase in vancomycin-induced nephrotoxicity reports. The purpose of this systematic literature review is to determine the nephrotoxicity potential of maintaining higher troughs in clinical practice. All studies pertaining to vancomycin-induced nephrotoxicity between 1996 and April 2012 were identified from PubMed, Embase, Cochrane Controlled Trial Registry, and Medline databases and analyzed according to Cochrane guidelines. Of the initial 240 studies identified, 38 were reviewed, and 15 studies met the inclusion criteria. Overall, higher troughs (>15 mg/liter) were associated with increased odds of nephrotoxicity (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.95 to 3.65) relative to lower troughs of <15 mg/liter. The relationship between a trough of >15 mg/liter and nephrotoxicity persisted when the analysis was restricted to studies that examined only initial trough concentrations (OR, 3.12; 95% CI, 1.81 to 5.37). The relationship between troughs of >15 mg/liter and nephrotoxicity persisted after adjustment for covariates known to independently increase the risk of a nephrotoxicity event. An incremental increase in nephrotoxicity was also observed with longer durations of vancomycin administration. Vancomycin-induced nephrotoxicity was reversible in the majority of cases, with short-term dialysis required only in 3% of nephrotoxic episodes. The collective literature indicates that an exposure-nephrotoxicity relationship for vancomycin exists. The probability of a nephrotoxic event increased as a function of the trough concentration and duration of therapy. Since its discovery in the 1950s, vancomycin has been a mainstay of therapy for serious Staphylococcus aureus infections. Although vancomycin was a second-line therapy early in its life cycle, it emerged as a first-line agent for infections due to methicillin-resistant S. aureus (MRSA) in the 1970s (1). Over the next several decades, its usage dramatically increased due to the explosion of MRSA in both the community and health care settings (2-4). Despite the recent availability of alternative agents, vancomycin still remains the treatment of choice for serious MRSA infections (5).Despite its widespread use, there are growing concerns about the future role of vancomycin, particularly among patients who have invasive MRSA infections with vancomycin MICs of Ͼ1 mg/ liter (6). Although host-and pathogen-related factors have been implicated as a cause, suboptimal vancomycin dosing has been suggested as an alternative explanation for the poorer outcomes among these patients. To counteract some of these concerns and to maximize the likelihood of achieving a 24-h ratio of area under the curve to MIC (AUC/MIC) of greater than 400, expert guidelines now recommend more-intensive vancomycin dosing and maintenan...

“…Minejima et al (21) showed that the AKIN criteria were more sensitive than traditional criteria in detecting vancomycin nephrotoxicity. In their opinion, early detection of vancomycin nephrotoxicity has the potential to improve management because it may lead to changes in management that halt the process of renal injury.…”

Section: Discussionmentioning

confidence: 99%

“…AKI was defined and staged according to RIFLE (18), AKIN (19), and KDIGO (20) criteria. For comparison, we also defined AKI using two traditional nephrotoxicity (NT) criteria (21). Since we did not have access to urinary output data, AKI diagnoses were based solely on the magnitude of the increases in SCr levels (Fig.…”

Section: Methodsmentioning

confidence: 99%

Incidence, Predictors, and Impact on Hospital Mortality of Amphotericin B Nephrotoxicity Defined Using Newer Acute Kidney Injury Diagnostic Criteria

Rocha

Kobayashi

Almeida

et al. 2015

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...