Kidney-lung cross-talk and acute kidney injury

Abstract

There is a growing appreciation for the role that acute kidney injury (AKI) plays in the propagation of critical illness. In children, AKI is not only an independent predictor of morbidity and mortality, but is also associated with especially negative outcomes when concurrent with acute lung injury (ALI). Experimental data provide evidence that kidney-lung crosstalk occurs and can be bidirectionally deleterious, although details of the precise molecular mechanisms involved in the AKI-ALI interaction remain incomplete. Clinically, ALI, and the subsequent clinical interventions used to stabilize gas exchange, carry consequences for the homeostasis of kidney function. Meanwhile, AKI negatively affects lung physiology significantly by altering the homeostasis of fluid balance, acid-base balance, and vascular tone. Experimental AKI research supports an "endocrine" role for the kidney, triggering a cascade of extra-renal inflammatory responses affecting lung homeostasis. In this review, we will discuss the pathophysiology of kidney-lung crosstalk, the multiple pathways by which AKI affects kidney-lung homeostasis, and discuss how these phenomena may be unique in critically ill children. Understanding how AKI may affect a "balance of communication" that exists between the kidneys and the lungs is requisite when managing critically ill children, in whom imbalance is the norm.

Fig. 1

The kidney plays a central role in supporting oxygen delivery. a Increases in preload (oliguric acute kidney injury) affect cardiac performance. b Afterload determined by renal effects on vascular tone affects stroke volume. c) Acid–base balance affects enzymatic function (black) and vascular resistance (red). d Control of erythropoietin affects oxygen-carrying capacity (CaO₂)

Fig. 2

The kidney “engine” is involved in the homeostatic regulation of numerous extra-renal organ beds through crosstalk. Acute kidney injury can lead to numerous derangements in each organ bed, both clinically evident (cl) and experimental (e). ICP intracranial pressure

Fig. 3

Acute kidney injury (AKI) significantly affects kidney–lung crosstalk. Through numerous mechanisms, both clinically manifest and subtle, AKI leads to aberrant kidney–lung homeostasis. DL_CO diffusion limitation of carbon monoxide—a marker of alveolar gas exchange capability, FVC forced vital capacity, FEV₁ forced exhaled volume in 1 s