Kidney-lung crosstalk in the critically ill patient

Abstract

Despite advances in renal replacement therapy, the mortality of acute kidney injury (AKI) has remained high, especially when associated with distant organ dysfunction such as acute lung injury (ALI). Mortality rates for combined AKI/ALI reach 80% in critically ill patients. While the clinical presentation of AKI-associated ALI is characterized by increased pulmonary edema, a defining feature of the syndrome, the AKI-induced lung effects extend beyond simple volume overload. Furthermore, ALI and associated mechanical ventilation frequently lead to a decline in renal hemodynamics, structure and function. New experimental data have emerged in recent years focusing on the interactive effects of kidney and lung dysfunction, and these studies have highlighted the pathophysiological importance of proinflammatory and proapoptotic pathways as well as the complex nature of interorgan crosstalk. This review will examine our current understanding of the deleterious kidney-lung crosstalk in the critically ill.

Fig. 1

Kidney-lung interactions during acute injury. AKI induces distant organ effects on the lung via cellular and soluble mediators. ALI, in turn, facilitates and exacerbates kidney dysfunction via metabolic and biomechanical derangements [, adapted from fig. 2].

Fig. 2

Biological processes activated in the lung following kidney ischemia. Gene ontology analysis of ischemia-specific lung genes identified early activation (Z > 2.0) of genes related to the innate immune response and cell adhesion bioprocesses, and later activation of genes related to response to stress and cell motility. Genes related to apoptosis and inflammation bioprocesses were activated across time points during ischemic AKI.