Two to Tango: Kidney-Lung Interaction in Acute Kidney Injury and Acute Respiratory Distress Syndrome

Abstract

Acute Kidney Injury (AKI) is an independent risk factor for mortality in hospitalized patients. AKI syndrome leads to fluid overload, electrolyte and acid-base disturbances, immunoparalysis, and propagates multiple organ dysfunction through organ “crosstalk”. Preclinical models suggest AKI causes acute lung injury (ALI), and conversely, mechanical ventilation and ALI cause AKI. In the clinical setting, respiratory complications are a key driver of increased mortality in patients with AKI, highlighting the bidirectional relationship. This article highlights the challenging and complex interactions between the lung and kidney in critically ill patients with AKI and acute respiratory distress syndrome (ARDS) and global implications of AKI. We discuss disease-specific molecular mediators and inflammatory pathways involved in organ crosstalk in the AKI-ARDS construct, and highlight the reciprocal hemodynamic effects of elevated pulmonary vascular resistance and central venous pressure (CVP) leading to renal hypoperfusion and pulmonary edema associated with fluid overload and increased right ventricular afterload. Finally, we discuss the notion of different ARDS “phenotypes” and the response to fluid overload, suggesting differential organ crosstalk in specific pathological states. While the directionality of effect remains challenging to distinguish at the bedside due to lag in diagnosis with conventional renal function markers and lack of tangible damage markers, this review provides a paradigm for understanding kidney-lung interactions in the critically ill patient.

Identification of kidney injury–released circulating osteopontin as causal agent of respiratory failure

“…In this regard, our study provides important insights. However, it is very much clinically recognized that ARDS is negatively affected by the presence of AKI ( 51 ) [reviewed in ( 52 )]. In this context, alveolar macrophages in ARDS patients highly express OPN ( 53 , 54 ), and lung macrophages also express OPN in an experimental mouse model of ALI/ARDS ( 53 ).…”

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

“…This review builds on and extends a number of excellent previous reviews of AKI–ALI [8,10,37–43]. For an expanded discussion on how AKI and ALI/ARDS interact, taking all clinically relevant physiological effects of AKI in particular reverse effects of ALI or its most severe form acute respiratory distress syndrome (ARDS) onto the kidney into account, the reader is referred to a recent excellent review [44]. Since publication of these reviews, newly recognized general interorgan crosstalk mechanisms and novel mediators of tissue injury‐induced lung injury have been described.…”

“…While clinically AKI‐induced ALI is likely underrecognized due to many confounders, such as co‐existing hypervolemia or cardiac dysfunction, which often serve as primary explanations for respiratory distress in AKI patients, it is very much clinically recognized that ARDS is significantly negatively affected by the presence of AKI [111] (reviewed in Ref. [44]). In this context, it is interesting to note that alveolar macrophages in ARDS patients highly express OPN [112,113], and lung macrophages also expressed OPN in an experimental mouse model of ALI/ARDS [112].…”

The Neglected Price of Pediatric Acute Kidney Injury: Non-renal Implications

“…Cellular and molecular mediators of lung injury have been described in the setting of AKI. The initial response to ischemic and nephrotoxic renal injury is mediated by macrophages and neutrophils and may lead to an unchecked pro-inflammatory state resulting in distant pulmonary injury (56)(57)(58)(59)(60)(61)(62)(63)(64). Ischemic renal injury in mice leads to an increase in circulating CD8+ Tcells in the lung along with increased markers of T-cell activation.…”

“…Furthermore, in infants born at ≥32 weeks gestation, AKI is independently associated with worse lung outcomes including higher likelihood of chronic lung disease and longer dependence on oxygen and respiratory support ( 92 ). For an in-detail review of the complex interaction between the lungs and kidney, the readers are referred to Alge et al ( 56 ).…”