Sepsis-induced AKI: From pathogenesis to therapeutic approaches

Abstract

Sepsis is a heterogenous and highly complex clinical syndrome, which is caused by infectious or noninfectious factors. Acute kidney injury (AKI) is one of the most common and severe complication of sepsis, and it is associated with high mortality and poor outcomes. Recent evidence has identified that autophagy participates in the pathophysiology of sepsis-associated AKI. Despite the use of antibiotics, the mortality rate is still at an extremely high level in patients with sepsis. Besides traditional treatments, many natural products, including phytochemicals and their derivatives, are proved to exert protective effects through multiple mechanisms, such as regulation of autophagy, inhibition of inflammation, fibrosis, and apoptosis, etc. Accumulating evidence has also shown that many pharmacological inhibitors might have potential therapeutic effects in sepsis-induced AKI. Hence, understanding the pathophysiology of sepsis-induced AKI may help to develop novel therapeutics to attenuate the complications of sepsis and lower the mortality rate. This review updates the recent progress of underlying pathophysiological mechanisms of sepsis-associated AKI, focuses specifically on autophagy, and summarizes the potential therapeutic effects of phytochemicals and pharmacological inhibitors.

Epigenetic dysregulation of autophagy in sepsis-induced acute kidney injury: the underlying mechanisms for renoprotection

“…The commonly affected organs include the heart, lungs, liver, brain, intestine, and kidneys. During sepsis, activation of the sympathetic nervous system, the release of vasoactive substances, and endothelial injury, together contribute to the redistribution of blood flow and microcirculation disturbances (3). These factors remarkably damage the kidney tissue (e.g.…”

Early warning value of urinary oxygen tension monitoring for paediatric intensive care unit sepsis-associated acute kidney injury: a retrospective study

“…Early studies suggested that the maintenance of renal function depended on renal perfusion with su cient renal blood ow, and renal underperfusion was considered the key to the occurrence of SA-AKI. However, in recent years, the mechanism of microcirculation damage has constantly challenged this paradigm standard [13]. AKI can occur even if early, aggressive rehydration maintains adequate renal blood perfusion.…”

Antioxidant, Antiapoptotic, and Anti-Inflammatory Effects of Hesperetin in a Mouse Model of Lipopolysaccharide-Induced Acute Kidney Injury

“…Sepsis can cause organ dysfunction and is a principal cause of death in critically ill patients. Acute kidney injury (AKI) is a common complication in septic patients, and about 60% of septic patients develop AKI [ 3 ]. Indeed, sepsis is a leading cause of AKI in critically ill patients and accounts for 45–70% of all AKI cases [ 3 ].…”

“…Acute kidney injury (AKI) is a common complication in septic patients, and about 60% of septic patients develop AKI [ 3 ]. Indeed, sepsis is a leading cause of AKI in critically ill patients and accounts for 45–70% of all AKI cases [ 3 ]. It has also well known that AKI is associated with an increased risk of developing chronic kidney disease [ 4 ].…”

“…It has also well known that AKI is associated with an increased risk of developing chronic kidney disease [ 4 ]. Current therapies for patients with septic AKI include antibiotics, fluid therapy, and vasopressors, but there is no specific treatment for the disease [ 3 ]. Therefore, the development of effective and specific therapeutic strategies for septic AKI is urgently needed.…”