Interorgan crosstalk mechanisms in disease: the case of acute kidney injury‐induced remote lung injury

Abstract

Homoeostasis and health of multicellular organisms with multiple organs depends on interorgan communication. Tissue injury in one organ disturbs this homoeostasis and can lead to disease in multiple organs, or multiorgan failure. Many routes of interorgan crosstalk during homoeostasis are relatively well known, but interorgan crosstalk in disease still lacks understanding. In particular, how tissue injury in one organ can drive injury at remote sites and trigger multiorgan failure with high mortality is poorly understood. As examples, acute kidney injury can trigger acute lung injury and cardiovascular dysfunction; pneumonia, sepsis or liver failure conversely can cause kidney failure; lung transplantation very frequently triggers acute kidney injury. Mechanistically, interorgan crosstalk after tissue injury could involve soluble mediators and their target receptors, cellular mediators, in particular immune cells, as well as newly identified neuro‐immune connections. In this review, I will focus the discussion of deleterious interorgan crosstalk and its mechanistic concepts on one example, acute kidney injury‐induced remote lung injury.

Development of a predictive nomogram for acute respiratory distress syndrome in patients with acute pancreatitis complicated with acute kidney injury

“…ARDS is a type of rapidly progressive respiratory failure characterized by diffuse alveolar damage that is often accompanied by apoptosis of epithelial cells, alveolar and interstitial pulmonary edema, inflammatory cell infiltration, and pulmonary microthrombosis [ 23 ]. The pathophysiologic link between ARDS and AKI has been investigated, inflammatory cytokine storm, oxidative stress and dysregulation of ion/water transport channels play a crucial role in the development of ARDS complicating AKI [ 24 ]. Alternatively, with its attendant hypoxemia and mechanical ventilation-associated high PEEP, ARDS could increase renal vascular resistance, redistribute renal blood flow and activate neurohormonal pathways, leading to deteriorative renal hemodynamics [ 25 ].…”

Organ Crosstalk in Acute Kidney Injury: Evidence and Mechanisms

“…Systemic inflammatory response syndrome (SIRS) characterized by increased levels of circulating cytokines and chemokines, including IL-1β, IL-6, IL-8, MCP-1, and TNF-α, was observed in AKI or ALI patients and animal models, which may cause lung and kidney inflammation, cell apoptosis, increases in endothelial barrier permeability, oxidative stress, and aggravation of pulmonary edema [33,34,41]. Among these pro-inflammatory factors, IL-6 was considered to be a more critical mediator of kidney-lung crosstalk, and IL-6 deficiency protected against AKI-induced lung injury via reductions in the level of IL-8 in lung and serum, thereby diminishing pneumonia and capillary leakage [42].…”

Human pulmonary microvascular endothelial cells respond to DAMPs from injured renal tubular cells

“…Acute kidney injury (AKI) causes distant organ dysfunction through yet unknown mechanisms, leading to multiorgan failure and death. The lungs are one of the most common extrarenal organs affected by AKI, 1 , 2 , 3 and combined lung and kidney injury has a mortality between 60% and 80%. 4 , 5 , 6 The mechanisms leading to lung injury after AKI are poorly understood and represent a potential avenue for new therapeutics aimed at ameliorating the devastating effects of AKI.…”