Background

Acute kidney injury (AKI) is now recognized as a major health problem affecting millions of patients globally. General estimates of the AKI incidence in the past varied, with data from different populations ranging from 114 to 174 people per 10,000 person-years, or approximately 13.3 million worldwide in 2017 [1, 2]. Reported AKI incidence is highest in low- and middle-income countries with AKI affecting approximately 15% of all hospitalized patients and about half of critically ill patients in the highest income areas [1, 2]. AKI is associated with not only increased mortality but also increased morbidity [3–5]. Patients who survive an episode of AKI have an increased risk of developing chronic kidney disease (CKD) [6–10]. Outcomes in AKI are affected not only by the original cause of the AKI, but also by the duration and severity of kidney dysfunction as well as the baseline status of the patient, including the presence of CKD.

Although kidney replacement therapy (KRT) is available, the cause of the high mortality rate in patients with severe AKI is still not fully elucidated. AKI is not an isolated organ failure of the kidney; rather, due to the kidney’s numerous functions, other organs are also affected. Injury of distant organs is considered an important cause of complication and mortality, given that multi-organ dysfunction is often observed in AKI patients and the number of organ dysfunctions is associated with increased mortality [11, 12]. Patients with a dialysis-dependent AKI have a considerably higher mortality rate compared to patients with end-stage kidney disease (ESKD) [13], suggesting that, in addition to impaired kidney function in AKI, other factors contribute to the poor prognosis. These data suggest that organ dysfunction induced by AKI plays a significant role in the prognosis of critically ill patients. Experimental studies have uncovered various mechanisms contributing to AKI-induced distant organ injury. Mechanisms involving the immune system, lungs, heart, liver, brain, and gut have been demonstrated. These mechanisms are organ-specific and diverse, encompassing immune cell responses, oxidative stress, and inflammatory cytokines. These organ interactions, established in animal studies, have been corroborated in clinical observational studies [12, 13].

This review article briefly outlines the molecular mechanisms of AKI-associated remote organ dysfunction, the epidemiology of complications, and the clinical outcomes reported in the literature. The final section discusses novel endpoints for AKI trials, taking into account organ interactions during AKI and the resulting complications.