Difference in nephrotoxicity of vancomycin administered once daily and twice daily in rats

Konishi, Hiroki; Morita, Yukiko; Mizumura, Miyo; Iga, Ikumi; Nagai, Katsutoshi

doi:10.1179/1973947812y.0000000067

Cited by 13 publications

(18 citation statements)

References 36 publications

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“…To date, animal models of AKI have confirmed that vancomycin is a nephrotoxin. Dose-ranging studies have revealed that an increase in the vancomycin dose and an increase in the duration of treatment in rats are associated with increases in histopathological damage and elevations in novel urinary biomarkers of AKI (8)(9)(10). However, a prospectively derived ex-posure-AKI (i.e., a pharmacokinetic [PK]/toxicodynamic [TD]) threshold for vancomycin has not been defined.…”

mentioning

confidence: 99%

Evaluation of Vancomycin Exposures Associated with Elevations in Novel Urinary Biomarkers of Acute Kidney Injury in Vancomycin-Treated Rats

Rhodes

Prozialeck

Lodise

et al. 2016

Antimicrob Agents Chemother

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Vancomycin has been associated with acute kidney injury (AKI).A cute kidney injury (AKI) is a major contributor to patient morbidity and mortality in the hospital setting (1, 2). While the etiology of AKI is multifactorial, many cases among hospital patients are related to medication exposure (2). Not surprisingly, the risk of drug-induced AKI is highest among critically ill, hospitalized patients (3), who carry multiple risk factors for the development and progression of AKI. Vancomycin, the antibiotic most frequently administered in the hospital setting (4), has been implicated as a cause of AKI in a number of clinical (5-7) and animal (8-10) studies. Among the clinical studies, the incidence of vancomycin-induced AKI has been associated with higher doses of vancomycin (11, 12), increasing numbers of vancomycin doses (12), and elevated trough concentrations (7, 13).While a number of clinical studies have shown that more intensive vancomycin dosing regimens are associated with an increased risk of AKI, these studies could only suggest an association with kidney injury. As these studies were largely observational in nature, it is difficult to discern if the association was reflective of a true effect or was biased due to confounders. For example, patient confounder factors, such as severity of illness, residence in an intensive care unit, and concurrent receipt of nephrotoxins, may influence the vancomycin exposure-response profile that best predicts clinical AKI.Animal systems are ideally suited to define exposure-response relationships, as they provide flexibility to titrate dosing groups and minimize the influence of external covariates on the observed results. To date, animal models of AKI have confirmed that vancomycin is a nephrotoxin. Dose-ranging studies have revealed that an increase in the vancomycin dose and an increase in the duration of treatment in rats are associated with increases in histopathological damage and elevations in novel urinary biomarkers of AKI (8-10). However, a prospectively derived ex-

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mentioning

confidence: 99%

Evaluation of Vancomycin Exposures Associated with Elevations in Novel Urinary Biomarkers of Acute Kidney Injury in Vancomycin-Treated Rats

Rhodes

Prozialeck

Lodise

et al. 2016

Antimicrob Agents Chemother

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“…Changes in body and kidney weights are valuable indicators of severe renal toxicity in the experimental models (6,8,9,33). In our experimental condition, VCM caused a significant reduction in the body weight and increased the ratio of average kidneys to 100 g body weight.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, phenolic and flavonoid contents of NOE detected to be 71 ± 6.23 gallic acid equivalents/g dried extract and 95.26 ± 7.6 mg rutin equivalents/g dried extract, respectively. Based on 6 Jundishapur J Nat Pharm Prod. In Press(In Press):e67178.…”

Section: Discussionmentioning

confidence: 99%

“…This dose of VCM was selected based on previous studies (4,6,8,9). The rats were weighed prior to the first injection of VCM and every other day in order to adjust the dose according to weight changes.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…One of the major adverse effects of this drug is nephrotoxicity, which has limited its dose and duration of administration (1,2). Although the exact mechanism of renal toxicity of VCM is not fully understood, some published studies have suggested that the oxidative stress has a crucial role in the pathogenesis of VCM-induced nephrotoxicity (VIN) (3)(4)(5)(6)(7). Several antioxidants including: vitamin E (8), 2, 3-dihydroxybenzoic acid (9), curcumin (10) and vitamin C (11) have been reported that reduces VIN.…”

Section: Introductionmentioning

confidence: 99%

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Nephroprotective Effect of Nasturtium Officinale (Watercress) Ethanol Extract and Vitamin E on Vancomycin-Induced Nephrotoxicity in Rats

Karami

Mostafazadeh

Sadeghi

et al. 2018

Jundishapur J Nat Pharm Prod

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Background: Vancomycin (VCM) is an important antibiotic that is active against gram-positive cocci, and its nephrotoxicity remain as a major problem in clinical use. Objectives: This study was designed to investigate the effect of Nasturtium officinale hydro-alcoholic extract (NOE) and vitamin E aganist VCM-induced nephrotoxicity in adult male wistar rats. Methods: A total of 36 animals were randomly divided into 6 equal groups (n = 6) including 1, control group; 2, VCM group; 3, VCM + NOE (250 mg/kg) group; 4, VCM + NOE (500 mg/kg) group; 5, VCM + vitamin E (250 mg/kg) group; and 6, VCM + vitamin E (500 mg/kg) group. VCM (200 mg kg -1 i.p.) was given every 12 hours for 7 consecutive days. NOE and vitamin E were orally given to rats 30

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Vancomycin‐Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention

et al. 2020

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Vancomycin is a recommended therapy in multiple national guidelines. Despite the common use, there is a poor understanding of the mechanistic drivers and potential modifiers of vancomycin-mediated kidney injury. In this review, historic and contemporary rates of vancomycin-induced kidney injury (VIKI) are described, and toxicodynamic models and mechanisms of toxicity from preclinical studies are reviewed. Aside from known clinical covariates that worsen VIKI, preclinical models have demonstrated that various factors impact VIKI, including dose, route of administration, and thresholds for pharmacokinetic parameters. The degree of acute kidney injury (AKI) is greatest with the intravenous route and higher doses that produce larger maximal concentrations and areas under the concentration curve. Troughs (i.e., minimum concentrations) have less of an impact. Mechanistically, preclinical studies have identified that VIKI is a result of drug accumulation in proximal tubule cells, which triggers cellular oxidative stress and apoptosis. Yet, there are several gaps in the knowledge that may represent viable targets to make vancomycin therapy less toxic. Potential strategies include prolonging infusions and lowering maximal concentrations, administration of antioxidants, administering agents that decrease cellular accumulation, and reformulating vancomycin to alter the renal clearance mechanism. Based on preclinical models and mechanisms of toxicity, we propose potential strategies to lessen VIKI.

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Difference in nephrotoxicity of vancomycin administered once daily and twice daily in rats

Cited by 13 publications

References 36 publications

Evaluation of Vancomycin Exposures Associated with Elevations in Novel Urinary Biomarkers of Acute Kidney Injury in Vancomycin-Treated Rats

Evaluation of Vancomycin Exposures Associated with Elevations in Novel Urinary Biomarkers of Acute Kidney Injury in Vancomycin-Treated Rats

Nephroprotective Effect of Nasturtium Officinale (Watercress) Ethanol Extract and Vitamin E on Vancomycin-Induced Nephrotoxicity in Rats

Vancomycin‐Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention

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