Multi-Omics Techniques Make it Possible to Analyze Sepsis-Associated Acute Kidney Injury Comprehensively

Abstract

Sepsis-associated acute kidney injury (SA-AKI) is a common complication in critically ill patients with high morbidity and mortality. SA-AKI varies considerably in disease presentation, progression, and response to treatment, highlighting the heterogeneity of the underlying biological mechanisms. In this review, we briefly describe the pathophysiology of SA-AKI, biomarkers, reference databases, and available omics techniques. Advances in omics technology allow for comprehensive analysis of SA-AKI, and the integration of multiple omics provides an opportunity to understand the information flow behind the disease. These approaches will drive a shift in current paradigms for the prevention, diagnosis, and staging and provide the renal community with significant advances in precision medicine in SA-AKI analysis.

Keywords: biomarkers; multi-omics integration; omics database; pathophysiology; sepsis-associated acute kidney injury.

Figure 1

Clinical course and pathophysiology of SA-AKI. Sepsis is the most common cause of AKI in critically ill patients. However, sepsis and AKI predispose hosts to each other, and it is often difficult to determine the exact timing of the onset of these two syndromes clinically. There is increasing evidence that the pathogenesis of SA-AKI is the “unified theory” theory involving the interaction between inflammation, microcirculation dysfunction, and metabolic reprogramming. The pathophysiology of SA-AKI involves injury and dysfunction of many cell types, including macrophages, ECs, and RTECs. PAMP and/or DAMP released from damaged tissues activate and promote the pro-inflammatory phenotype (M1) of macrophages, resulting in the release of pro-inflammatory cytokines and chemokines, which can cause damage to kidney tissues. The second cell type that is vulnerable is the EC. Sepsis stimulates endothelial cells to produce nitric oxide, which causes blood vessels to dilate. Many molecules simultaneously control microvascular permeability, resulting in insufficient blood volume relative to the vessel when tight cellular connections loosen. In addition, during the period of sepsis, confirmed microvascular thrombosis related to inflammation. In RTECs, infiltration of inflammatory cells and a large number of inflammatory factors lead to deterioration of renal function, apoptotic cell death, and sublethal injury.

Figure 2

Schematic representation of a multi-omics approach to SA-AKI. Single omics data can be integrated into multiple-omics and combined with systems biology to understand the pathophysiological mechanisms of SA-AKI better and facilitate the discovery and development of emerging biomarkers for treatment.