Due to inter-organ crosstalk, which is an essential part of human biology, a damaged organ generally compromises other organs in critically ill patients. Acute kidney injury (AKI) is characterized by an acute drop in glomerular filtration rate, diagnosed by either an increase in serum creatinine and/or development of oliguria, reflected in the diagnostic criteria of the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. AKI results in fluid retention, electrolyte disturbance, metabolic acidosis, and altered drug pharmacokinetics. Inflammatory mediator clearance is also reduced, resulting in a significantly increased pro-inflammatory burden [1]. This, in combination with the accumulation of uremic toxins, contributes to endothelial injury and increased vascular permeability [2]. In addition to renal loss of function, renal stress and/or damage, which may precede AKI diagnosis (subclinical AKI), may also induce inflammation and have remote consequences [3]. These consequences might vary according the underlying AKI cause.

The present article proposes a nephrocentric view regarding the impact of AKI on the function of essential organs (Fig. 1). Although AKI may affect nearly every organ in the body, this review will focus on the most documented interactions and clinically relevant organs.

Fig. 1
figure 1

Impact of AKI on other organ systems

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AKI and the immune system

Clinical data suggest an association between AKI and subsequent dysregulation of the immune system, leading notably to an increased risk of sepsis and transition from AKI to chronic kidney disease (CKD)[3]. Both molecular and cellular effectors may play a role in AKI-associated inflammation. First, AKI has profound effects on cytokine homeostasis. During systemic inflammation, loss of renal function may decrease cytokine clearance, thereby leading to an increased level of inflammatory molecules and further aggravating systemic inflammation [1]. In experimental models, a large panel of inflammatory cytokines including IL6, IL8, and TNF-alpha was increased during AKI. In the clinical setting of trauma, higher plasma levels of IL6, IL8, IL1ra, and chemoattractant protein-1 were found in patients with AKI compared to those without AKI [4]. In addition, it has been suggested that renal tubular cells may also release inflammatory cytokines during AKI [5]. Second, impaired recruitment of neutrophils associated with AKI may impact the inflammatory response, implying a possible AKI-induced anti-inflammatory effect. Results from experimental analyses suggest compromised rolling and migration of neutrophils [6].

AKI and the heart

Cardiorenal syndrome (CRS) defines the complex bidirectional interactions between the heart and kidneys, and CRS type 3 defines cardiac dysfunction resulting from AKI [7]. The pathophysiological mechanisms by which AKI contributes to acute cardiac dysfunction are not well known. Some experimental data suggest that cardiac injury may be directly triggered by inflammatory mediators, oxidative stress, and upregulation of neuroendocrine systems early after AKI. Among the physiological disturbances associated with loss of renal function, fluid overload is of particular importance as it increases preload and stretches cardiomyocytes, thereby diminishing contractility and increasing work demand. In patients with acidemia, accumulated acid may alter protein structure and impair normal function, leading to decreased myocardial contractility through altered expression of β-receptors and mishandling of intracellular calcium. AKI-based electrolyte disorders can cause cardiac arrhythmias, thus decreasing cardiac output and putting patients at risk of thrombotic events. Furthermore, both the renin–angiotensin–aldosterone and central nervous systems are activated in AKI, leading to increased fluid retention, increasing pre- and afterload [7]. In terms of uremia, although little is known about the effect of uremic toxins on cardiac function in AKI, an association with cardiovascular toxicity has been demonstrated in CKD [2]. In addition, AKI contributes to alterations in cardiovascular drug pharmacokinetics and pharmacodynamics.

AKI and the lung

The effects of AKI on the lung may be related to immune-mediated effects, fluid retention, and electrolyte abnormalities [8]. In animal models of renal ischemia–reperfusion injury (IRI), changes have been reported in the lung inflammasome as well as in the lung metabolome reflecting oxidative stress and energy depletion [9]. Furthermore, a reduced pulmonary expression of ENaC, Na, K-ATPase, and aquaporin-5 has been observed in these models, thus impacting alveolar fluid resorption [10]. Additionally, fluid retention increases extravascular lung water and consequently alveolar fluid content, resulting in impaired oxygenation. Clinical studies demonstrated an association between AKI and pneumonia and sepsis severity. In case of AKI, time on mechanical ventilation and mortality are increased in patients with acute respiratory distress syndrome [8]. Furthermore, metabolic acidosis requires an increase in ventilator drive and tidal volume for respiratory compensation, thereby increasing the risk of both self-inflicted and ventilator-induced lung injury. This may be particularly relevant in patients with chronic obstructive pulmonary disease for whom renal compensation of respiratory acidosis is essential.

AKI and the gut

Because it contains hundreds of microbiota species and more than half of the body’s immune cells, the gastrointestinal tract is central for homeostasis. In experimental animal models of IRI, the gut microbiota was consistently modified, within 24 h. This dysbiosis reduced the amount of bacterial fermentation products contained in the lumen, such as short chain fatty acids (SCFA) that play a pivotal role in mitigating inflammation and gut-organ crosstalks, thus increasing inflammation. Experimental models of AKI also display an infiltration and activation of innate immune cells in the gut walls, where lymphocytes adopt a more inflammatory phenotype. It is hypothesized that AKI-associated fluid overload and uremia can modify the epithelial cells tight junctions, increasing gut permeability [3]. Altogether, microbiota dysbiosis, wall edema, and inflammation are the main consequences of AKI on gut function and permeability. The subsequent translocation of pathogens and endotoxins into the circulation further enhances the systemic inflammation and kidney injury. AKI-induced dysbiosis may also play a pivotal role in the transition to CKD. Among other reported long-term effects is the increased risk of upper gastrointestinal bleeding after AKI requiring renal replacement therapy (RRT) [11]. Recent innovative approaches targeting the microbiota aim to modulate AKI-associated inflammation.

AKI and the brain

It is well established that encephalopathy is a major symptom of uremia, partly correlating with blood urea nitrogen levels. Although full-blown uremia is a rare event in well-treated AKI, the accumulation of even low levels of uremic toxins may still impair cognitive function in critically ill patients, in a more pronounced and rapidly progressing manner than in patients with CKD [2]. In adult critically ill patients, AKI KDIGO stages 2 and 3 are associated with a nearly two-fold increased risk of delirium and coma [12]. In preterm infants, AKI is associated with brain insult, especially in the cerebellum [13]. AKI-associated encephalopathy may result from elevated systemic cytokine levels as well as increased oxidative stress in the brain, further enhanced by renal sympathetic afferent nerve stimulation. These factors may also play a role in changes of the blood brain barrier observed in animal experiments, the effect of which may be exacerbated by altered aquaporin 1 and 4 expression. Finally, altered metabolism of centrally active drugs has to be considered.

AKI and the liver

Contrary to the hepatorenal syndrome, the effects of AKI on liver function remain largely unknown. Small animal models display liver histopathological changes following renal IRI or nephrectomy. The main features are tissue infiltration by inflammatory cells and mediators such as TNF-α and IL-6, hepatocyte injury and necrosis, and oxidative stress [14]. Recently, a transient elevation of liver enzymes, such as amino acid transferases, was observed after ischemic AKI in pigs. Interestingly, changes in the liver tissue were only mild and totally disappeared 5 weeks later, suggesting a moderate and transient injury [15]. However, AKI remains clinically relevant for liver function. Loss of renal function may affect the liver cytochrome enzyme system through metabolic acidosis and uremia, resulting in altered drug elimination. Hepatic congestion and failure may also occur secondary to fluid accumulation in oligo-anuric AKI [14].


AKI impacts remote organs through various pathways such as inflammation mediated by cellular and molecular effectors, metabolic and hemodynamic alterations, and the neurohormonal system. When the kidney suffers, remote organs also suffer, likely contributing to the AKI-associated mortality and morbidity. Interventions aiming at mitigating kidney-organ crosstalks might be considered to improve patient outcomes. This however, requires a better understanding of the interactions between organs, which to date rely mainly on animal models or CKD patients, and do not account for AKI causes and severity. The damages caused by renal loss of function or kidney injury itself also need to be distinguished.