Natural products for the prevention of antibiotic-associated kidney injury.

Drug-induced acute kidney injury (AKI), especially from exposure to antibiotics, has a high prevalence secondary to their frequent prescription. Typically, drug-induced AKI results from acute tubular necrosis or acute interstitial nephritis. While some risk factors for the development of AKI in individuals treated with antibiotics are modifiable, others such as concomitant drug therapies to treat comorbidities, age, and pre-existing chronic kidney disease are not modifiable. As such, there is an urgent need to identify strategies to reduce the risk of AKI in individuals requiring antibiotic therapy. Natural products, especially those rich in active constituents possessing antioxidant properties are an attractive option to mitigate AKI risk. Given that mitochondrial dysfunction precedes AKI and natural products can restore mitochondrial health and counter the oxidative stress secondary to mitochondrial damage investigating their utility warrants further attention. The following review summarizes the available preclinical and clinical evidence that provides a foundation for future study.

Renoprotective Effects of Melatonin against Vancomycin-Related Acute Kidney Injury in Hospitalized Patients: a Retrospective Cohort Study.

Vancomycin is associated with nephrotoxicity, and the mechanism may in part be related to oxidative stress. In vitro and preclinical studies suggest that melatonin supplementation decreases oxidative stress. The objective of this study was to evaluate concomitant use of melatonin and vancomycin and the incidence of acute kidney injury (AKI). We performed a retrospective cohort study at a large community medical center. All consecutive patients admitted to the medical center between January 2016 and September 2020 who received vancomycin therapy alone or concomitantly with melatonin as part of ordinary care were considered for inclusion. The primary endpoint was the development of AKI, defined as an absolute increase in serum creatinine of ≥0.3 mg/dl or a ≥50% increase in serum creatinine. All data were analyzed using descriptive statistics. A multivariable logistic regression was constructed to account for potential confounding variables. We identified a total of 303 adult patients meeting inclusion and exclusion criteria treated with vancomycin, 101 of which received melatonin concomitantly. Overall baseline characteristics were similar between the two groups except for the incidence of bacteremia/sepsis. After controlling for the vancomycin area under the curve, baseline creatinine clearance, and intensive care unit admission in a multivariable logistic regression analysis, melatonin use was associated with a 63% decrease in AKI (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.14 to 0.96; P = 0.041). Melatonin use was associated with a significant reduction in vancomycin-related AKI. Although this was a retrospective study with a small sample size, given the magnitude of the difference seen, further large prospective studies are warranted.

Face-to-Face: Resident-led Radiology Medicine Rounds Facilitate Evidence-based Processes for Clinical Decision Support.

BACKGROUND: The transition toward value-based payment models increases focus on the radiologist's direct impact on hospital-provided patient care. Radiology trainees understand inpatient hospital workflows and decision-making paradigms and are well positioned to interface directly with hospital physicians regarding clinical decision making related to diagnostic imaging and/or image guided interventions. A radiology resident-led project with internal medicine residents focused on Clinical Decision Support was designed, implemented, and reviewed, with the objectives of educating clinical teams and positively impacting patient care. MATERIALS AND METHODS: During the 2017-2018 academic year, senior radiology residents (PGY-5) led weekly rounds with medicine residents rotating through inpatient floor units. During these rounds, they discussed indications for and types of hospital inpatient imaging studies, exchanged clinical information, directed further imaging workup, and taught the essentials of image interpretation. Participating medical residents' degree of radiology-awareness and opinions were systematically surveyed at the conclusion of the academic year. Thirty-four out of a total of 161 (21%) Internal Medicine residents responded to the survey. Thirty one percent of these residents could identify an instance where radiology-led rounds altered patient management and 94% acknowledged an increase in medical knowledge. Sixty-one percent believed evidence-based choice for imaging orders was enhanced by attending radiology-led rounds and 64% developed a better understanding of resources available to guide image ordering. Forty-nine percent of residents made suggestions to their Internal Medicine attending physician or more senior trainee or otherwise applied something learned during radiology-led rounds and 42% cancelled or ordered a study based on what they learned or discussed in radiology rounds. Thirty-nine percent of medicine residents stated that these rounds changed their perception of the role of the radiologist and 75% expressed the desire to see increased participation by radiologists in their daily workflow. Radiology resident-led educational medicine rounds promote cross-specialty collaboration, further educate trainees, and directly affect patient management. It is therefore valuable for radiology trainees to directly engage in the teaching of other medical providers, to enhance their own consultative skill set, promote face-to-face interactions with other physicians, and to directly impact patient care.

The molecular structure of ornithine acetyltransferase from Mycobacterium tuberculosis bound to ornithine, a competitive inhibitor.

Mycobacterium tuberculosis ornithine acetyltransferase (Mtb OAT; E.C. 2.3.1.35) is a key enzyme of the acetyl recycling pathway during arginine biosynthesis. It reversibly catalyzes the transfer of the acetyl group from N-acetylornithine (NAORN) to L-glutamate. Mtb OAT is a member of the N-terminal nucleophile fold family of enzymes. The crystal structures of Mtb OAT in native form and in its complex with ornithine (ORN) have been determined at 1.7 and 2.4 A resolutions, respectively. ORN is a competitive inhibitor of this enzyme against L-glutamate as substrate. Although the acyl-enzyme complex of Streptomyces clavuligerus ornithine acetyltransferase has been determined, ours is the first crystal structure to be reported of an ornithine acetyltransferase in complex with an inhibitor. ORN binding does not alter the structure of Mtb OAT globally. However, its presence stabilizes the three C-terminal residues that are disordered and not observed in the native structure. Also, stabilization of the C-terminal residues by ORN reduces the size of the active-site pocket volume in the structure of the ORN complex. The interactions of ORN and the protein residues of Mtb OAT unambiguously delineate the active-site residues of this enzyme in Mtb. Moreover, modeling studies carried out with NAORN based on the structure of the ORN-Mtb OAT complex reveal important interactions of the carbonyl oxygen of the acetyl group of NAORN with the main-chain nitrogen atom of Gly128 and with the side-chain oxygen of Thr127. These interactions likely help in the stabilization of oxyanion formation during enzymatic reaction and also will polarize the carbonyl carbon-oxygen bond, thereby enabling the side-chain atom O(gamma 1) of Thr200 to launch a nucleophilic attack on the carbonyl-carbon atom of the acetyl group of NAORN.