Organ Crosstalk During Injury: Mechanisms of Lung-Kidney Interaction in Critical Illness

The kidneys and lungs are frequent sites of organ injury during critical illness. Acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS) are clinical syndromes resulting from kidney and lung injury respectively. Complex pathophysiologic mechanisms underlie the development of these two syndromes individually, and a substantial body of evidence now indicates that crosstalk between the lungs and the kidneys occurs after organ injury. Here we review the pathophysiology of AKI and ARDS, animal models of kidney and lung injury, and mechanisms of organ crosstalk after injury has occurred. We focus the discussion on how either kidney injury or lung injury may propagate damage in the other organ, which is relevant to multiorgan injury commonly encountered in the intensive care unit. The reviewed literature contains more mechanistic preclinical studies of lung injury after AKI compared with AKI after lung injury. Identified mechanisms of lung injury after AKI include leukocyte recruitment, inflammatory signaling, activation of pattern recognition receptors, formation of neutrophil extracellular traps, osteopontin signaling, metabolic dysfunction, and impaired alveolar fluid clearance. After lung injury, AKI is instigated by inflammatory signaling, the effects of mechanical ventilation, and consequences of fluid management.