<p>Serum Concentration of Vancomycin Is a Diagnostic Predictor of Nephrotoxic Acute Kidney Injury in Septic Patients in Clinical and Surgical Wards</p>

Abstract

Introduction and Aim: There have been few studies to evaluate the monitoring of plasmatic concentrations of vancomycin in septic patients and their association with acute kidney injury (AKI) and death. This study aimed to evaluate the prevalence of adequate, subtherapeutic, and toxic serum concentrations of vancomycin in hospitalized septic patients and to associate the adequacy of therapeutic monitoring with clinical outcomes. Methodology: This was a cohort-unicentric study that evaluated septic patients aged >18 years using vancomycin admitted to clinical and surgical wards of a Brazilian university center from August 2016 to July 2017 in a daily and uninterrupted way. We excluded patients with AKI prior to the introduction of vancomycin or with AKI development <48 hours after use, patients with AKI of other etiologies, stage V chronic kidney disease, and pregnant women. Results: We evaluated 225 patients, and 135 were included. Evaluation of serum concentration of vancomycin was realized in 94.1%, and of those, 59.3% presented toxic concentrations. The prevalence of AKI was 27.4% and happened on average on the ninth day of vancomycin usage. Between the fourth and sixth days, vancomycin serum concentration of >21.5 mg/L was a predictor of AKI, with area under the curve of 0.803 (95% CI 0.62-0.98, p=0.005), preceding the diagnosis of AKI by at least 3 days. Of these patients, 20.7% died, and serum concentrations of vancomycin between the fourth and sixth days were identified as risk factors associated with negative outcomes. Conclusion: Serum concentration of vancomycin is an excellent predictor of AKI in patients admitted to wards, preceding the diagnosis of AKI by at least 72 hours. Toxic concentrations of vancomycin are associated with AKI, and AKI was a risk factor for death. Also, serum concentration of vancomycin >21.5 mg/L was the only variable associated with death in the Cox model.

The Role of Urinary Biomarkers as Diagnostic and Prognostic Predictors of Acute Kidney Injury Associated With Vancomycin

“…Among the population studied, the incidence of AKI was 24.5%, with a predominance of KDIGO 1 (61%) and mortality of 8.7%, which indicates that we really studied without AKI associated with sepsis, in which mortality is much higher, around 35% ( Srisawat and Kellum, 2011 ). Data from the previous studies suggest variable nephrotoxicity prevalence, from 5 to 40% in the presence of other nephrotoxic drugs ( Elyasi et al, 2012 ; Hanrahan et al, 2014 ; Pazhayattil and Shirali, 2014 ; Funk et al, 2016 ; Zamoner et al, 2020 ).…”

“…Emphasis has been given to its nephrotoxicity, with the risk of AKI with short- and long-term complications. Ninety-four patients were included while 114 were excluded, mainly because they already had AKI before using vancomycin (81) or because of the difficulty in urinary collection ( Funk et al, 2016 ), which reflects the difficulty in studying the role of vancomycin nephrotoxicity, leading to doubt whether the high serum vancomycin concentrations are the cause or the consequence of AKI ( Bosso et al, 2011 ; Elyasi et al, 2012 ; Hanrahan et al, 2014 ; Zamoner et al, 2020 ).…”

“…Bosso et al ( Hirsch et al, 2007 ) performed a study that evaluated 288 patients using vancomycin and showed an association between nephrotoxicity incidence and vancomycin concentrations, with AKI occurring in almost 30% of patients with plasmatic concentrations of vancomycin >15 mg/L and 9% of patients with vancomycin concentrations <15 mg/L. Recently, Zamoner et al ( 2020 ) found that plasmatic concentration of vancomycin was an excellent predictor of AKI in patients admitted to wards, preceding the diagnosis of AKI by at least 72 h.…”

“…Regarding safety, emphasis has been given to the main side effect of the medication—nephrotoxicity—which can aggravate the clinical picture and contribute to unfavorable outcomes and occurs 4–8 days after starting to use. The pathophysiological mechanisms are not yet fully understood, but undoubtedly it is ongoing with a consequent worsening of the prognosis of these patients ( Zamoner et al, 2020 ).…”

“…The incidence of vancomycin nephrotoxicity varies widely between different studies, reaching up to 40% and there are different factors related to the patient and/or the drug that can accelerate the nephrotoxicity. Among the factors associated with the patient, we highlight, mainly, advanced age, sepsis, dehydration, and reduced kidney function, while among the risk factors related to the drug are the concomitant administration with other drugs such as loop diuretics, amphotericin B, aminoglycosides, vasopressors, and intravenous contrast media; the longer duration of treatment and the high plasmatic vancomycin concentration ( Elyasi et al, 2012 ; Zamoner et al, 2020 ).…”