RESUMO
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.
RESUMO
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.