Natural products for the prevention of antibiotic-associated kidney injury

Abstract

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.

Keywords: Acute kidney injury; Antibiotics; Natural products; Oxidative stress.

Figure 1

Medications may cause acute kidney injury by a variety of mechanisms. The pathophysiology can be categorized into two main categories – acute interstitial nephritis (AIN) and acute tubular necrosis (ATN). Right panel: AIN results secondary to T-cell mediated hypersensitivity. Toxin deposits in the interstitium bind to proteins forming haptens and activating the immune cascade. Macrophages present the antigens to T-cells resulting in their activation. In turn, the infiltrating activated immune cells release chemokines and cytokines resulting in damage to the nephron. Left panel: ATN is precipitated by exposure of the proximal tubule cells to a toxin. This exposure triggers mitochondrial stress, production of reactive oxidative species (ROS), activation of the inflammasome, and chemokine and cytokine release. Ultimately, mitochondrial dysfunction, cell apoptosis, lipid peroxidation, and calcium imbalance lead to the manifestation as acute kidney injury. Natural products may mitigate the cascade of events through NRF2 activation and restoration of mitochondrial health.