Impact of acute kidney injury on distant organ function: recent findings and potential therapeutic targets

Abstract

Acute kidney injury (AKI) is a common complication in critically ill patients and subsequently worsens outcomes. Although many drugs to prevent and treat AKI have shown benefits in preclinical models, no specific agent has been shown to benefit AKI in humans. Moreover, despite remarkable advances in dialysis techniques that enable management of AKI in hemodynamically unstable patients with shock, dialysis-requiring severe AKI is still associated with an unacceptably high mortality rate. Thus, focusing only on kidney damage and loss of renal function has not been sufficient to improve outcomes of patients with AKI. Recent data from basic and clinical research have begun to elucidate complex organ interactions in AKI between kidney and distant organs, including heart, lung, spleen, brain, liver, and gut. This review serves to update the topic of organ cross talk in AKI and focuses on potential therapeutic targets to improve patient outcomes during AKI-associated multiple organ failure.

Gut microbiome in chronic kidney disease: challenges and opportunities

“…Rhabb et al (111) showed that germfree mice have increased susceptibility to ischemia and reperfusion injury (IRI), which is reversed by colonization with commensal bacteria. This observation suggests that certain gut microbiota products might be protecting against IRI (112).…”

The Role of BCL-2 Family Members in Acute Kidney Injury

“…Furthermore, apoptosis within the renal parenchyma exerts profound untoward effects, including apoptosis in distant organs, 158 including the brain, lung, liver, and heart. [78][79][80][159][160][161] It is likely that apoptosis (and perhaps necrosis) occurring outside the kidney is mediated by BCL-2 proteins and may be amenable to systemic manipulation directed at preventing conformational bax activation and/or the decrease in bcl-2 caused by renal stress.…”

Kidney-Heart Interactions in Acute Kidney Injury

“…Focusing only on kidney damage may not be sufficient to improve outcomes of patients with AKI. Recent studies have elucidated complex organ interactions in AKI between the kidneys and distant organs [15]. We further need to identify unrecognized organ interactions in AKI, such as mitochondria injury in the heart, to develop novel therapeutics against AKI and decrease the high mortality rate during AKI-related multiple organ failure.…”