scholarly journals Of Rats and Men, a Translational Model to Understand Vancomycin Pharmacokinetic/Toxicodynamic relationships.

2021 ◽  
Author(s):  
Marc H. Scheetz ◽  
Gwendolyn Pais ◽  
Thomas P. Lodise ◽  
Steven Y.C. Tong ◽  
Joshua S. Davis ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Rat Model ◽  
Clinical Studies ◽  
Kidney Injury ◽  
Concentration Curve ◽  
Translational Model ◽  
Link Model

Vancomycin area under the concentration curve (AUC) is known to predict vancomycin induced acute kidney injury (AKI). Data were analyzed from a rat model (n=48) and two prospective clinical studies [PROVIDE (n=263) and CAMERA2 (n=291)]. A logit-link model was used to calculate the multiplicative factors between the probability of AKI from clinical studies and the rat. The rat was 2.7 to 4.2 times more sensitive to AKI between AUCs of 199.5 and 794.3 mg*h/L, respectively.

scholarly journals Of Rats and Men, a Translational Model to Understand Vancomycin Pharmacokinetic/Toxicodynamic relationships

2021 ◽  
Author(s):  
Marc H. Scheetz ◽  
Gwendolyn Pais ◽  
Thomas P. Lodise ◽  
Steven Y.C. Tong ◽  
Joshua S. Davis ◽  
...  
Keyword(s):  
Therapeutic Range ◽  
Rat Model ◽  
Clinical Studies ◽  
Linear Models ◽  
External Validation ◽  
Hospital Setting ◽  
Kidney Injury ◽  
The United States ◽  
Concentration Curve ◽  
Clinical Model

AbstractBackgroundVancomycin is a first line antibiotic for many common infectious diseases and is the most commonly prescribed antibiotic in the United States hospital setting. Vancomycin is also well known to cause kidney injury; two recent prospective studies have identified that increasing vancomycin area under the concentration curve predicts vancomycin induced kidney injury (VIKI). However, outside of clinical trials, it is unclear if pre-clinical data can quantitatively describe VIKI in patients.MethodsData were simultaneously analyzed from a pre-clinical rat model and two prospective clinical studies. Logged vancomycin area under the concentration curve (AUC) data for rats (n=48) and patients from PROVIDE (n=263) and CAMERA2 (n=291) were included. VIKI was defined as urinary KIM-1 concentrations ≥9.42 ng/mL in the rat and according to KDIGO stage 1 kidney injury for all human patients. Multiple generalized linear models were explored, and the order of magnitude was calculated between the probability of acute kidney injury (AKI) from the average obtained in the clinical studies (i.e. CAMERA2 and PROVIDE) and the rat for 0.1 increments in Log10AUC bounded common concentrations obtained in the therapeutic range (i.e. ~200 −800 mg*24h/L).ResultsA logit link model best fit the data. When calculating the multiplicative factors between the studies therapeutic range AUCs, the rat was an average 2.7 to 4.2 times more sensitive to AKI between AUCs of 199.5 (i.e. log 10 AUC=2.3) and 794.3 mg*h/L (i.e. log 10 AUC=2.9), respectively.ConclusionsA pre-clinical rat model was quantitatively linked to toxicity data from two large human studies. The rat is an attractive pre-clinical model to explore exposure toxicity relationships with vancomycin. External validation is required.

Metabolomic profiling of urine-derived extracellular vesicles from rat model of drug-induced acute kidney injury

2021 ◽  
Vol 546 ◽  
pp. 103-110
Author(s):  
Masayoshi Saito ◽  
Satoshi Horie ◽  
Hidenori Yasuhara ◽  
Akane Kashimura ◽  
Eiji Sugiyama ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Extracellular Vesicles ◽  
Rat Model ◽  
Kidney Injury ◽  
Drug Induced ◽  
Metabolomic Profiling

Reno-protective effects of TAK-242 on acute kidney injury in a rat model

2018 ◽  
Vol 503 (1) ◽  
pp. 304-308 ◽  
Author(s):  
Bassim I. Mohammad ◽  
Abdulla K. Raheem ◽  
Najah R. Hadi ◽  
Dina A. Jamil ◽  
Hayder A. Al-Aubaidy
Keyword(s):  
Acute Kidney Injury ◽  
Rat Model ◽  
Kidney Injury ◽  
Protective Effects

Pathophysiological mechanisms underlying a rat model of triple whammy acute kidney injury

2020 ◽  
Vol 100 (11) ◽  
pp. 1455-1464
Author(s):  
Laura Prieto-García ◽  
Laura Vicente-Vicente ◽  
Víctor Blanco-Gozalo ◽  
Omar Hidalgo-Thomas ◽  
María C. García-Macías ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Rat Model ◽  
Kidney Injury ◽  
Pathophysiological Mechanisms

Comparison of iohexol and iodixanol induced nephrotoxicity, mitochondrial damage and mitophagy in a new contrast-induced acute kidney injury rat model

2018 ◽  
Vol 92 (7) ◽  
pp. 2245-2257 ◽  
Author(s):  
Wei Cheng ◽  
Fei Zhao ◽  
Cheng-Yuan Tang ◽  
Xu-Wei Li ◽  
Min Luo ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Rat Model ◽  
Kidney Injury ◽  
Mitochondrial Damage

LncRNA NEAT1 regulated inflammation and apoptosis in a rat model of sepsis-induced acute kidney injury via MiR-27a-3p/TAB3 axis

2020 ◽  
Vol 84 (11) ◽  
pp. 2215-2227
Author(s):  
Jiasheng Wang ◽  
Yong Chen ◽  
Ze Tang ◽  
Dabi Hu ◽  
Caoyuan Yao ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Rat Model ◽  
Kidney Injury ◽  
Lncrna Neat1

Troxerutin down-regulates KIM-1, modulates p38 MAPK signaling, and enhances renal regenerative capacity in a rat model of gentamycin-induced acute kidney injury

2018 ◽  
Vol 9 (12) ◽  
pp. 6632-6642 ◽  
Author(s):  
Samir A. Salama ◽  
Hany H. Arab ◽  
Ibrahim A. Maghrabi
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
P38 Mapk ◽  
Tissue Regeneration ◽  
Rat Model ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Mapk Signaling ◽  
Regenerative Capacity

Troxerutin enhances renal tissue regeneration, improves renal function, and decreases renal tissue injury in gentamycin-treated rats.

scholarly journals Resveratrol attenuates acute kidney injury by inhibiting death receptor-mediated apoptotic pathways in a cisplatin-induced rat model

2016 ◽  
Vol 14 (4) ◽  
pp. 3683-3689 ◽  
Author(s):  
Qiufa Hao ◽  
Xiaoyan Xiao ◽  
Junhui Zhen ◽  
Jinbo Feng ◽  
Chun Song ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Rat Model ◽  
Death Receptor ◽  
Kidney Injury ◽  
Apoptotic Pathways
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