New Frontiers in Sepsis-Induced Acute Kidney Injury and Blood Purification Therapies: The Role of Polymethylmethacrylate Membrane Hemofilter

Abstract

Acute kidney injury (AKI) is a common consequence of sepsis with a mortality rate of up to 40%. The pathogenesis of septic AKI is complex and involves several mechanisms leading to exacerbated inflammatory response associated with renal injury. A large body of evidence suggests that inflammation is tightly linked to AKI through bidirectional interaction between renal and immune cells. Preclinical data from our and other laboratories have identified in complement system activation a crucial mediator of AKI. Partial recovery following AKI could lead to long-term consequences that predispose to chronic dysfunction and may also accelerate the progression of preexisting chronic kidney disease. Recent findings have revealed striking morphological and functional changes in renal parenchymal cells induced by mitochondrial dysfunction, cell cycle arrest via the activation of signaling pathways involved in aging process, microvascular rarefaction, and early fibrosis. Although major advances have been made in our understanding of the pathophysiology of AKI, there are no available preventive and therapeutic strategies in this field. The identification of ideal clinical biomarkers for AKI enables prompt and effective therapeutic strategy that could prevent the progression of renal injury and promote repair process. Therefore, the use of novel biomarkers associated with clinical and functional criteria could provide early interventions and better outcome. Several new drugs for AKI are currently being investigated; however, the complexity of this disease might explain the failure of pharmacological intervention targeting just one of the many systems involved. The hypothesis that blood purification could improve the outcome of septic AKI has attracted much attention. New relevant findings on the role of polymethylmethacrylate-based continuous veno-venous hemofiltration in septic AKI have been reported. Herein, we provide a comprehensive literature review on advances in the pathophysiology of septic AKI and potential therapeutic approaches in this field.

Acute Kidney Injury in Kidney Transplant Patients in Intensive Care Unit: From Pathogenesis to Clinical Management

“…Several studies have also shown that E. coli infections result in site-specific endothelial dysfunction at the renal proximal tubule through bacterial attachment to the apical tubular cells membrane, with consequent local reduction in peritubular blood flow and increased endothelial permeability [81][82][83]. Specific pathogen-associated molecular patterns (PAMPs) are able to bind Pattern Recognition Receptors (PRRs) located on both immune cells and proximal tubular cells [84][85][86], such as the Toll-like receptors (TLRs), leading to Nuclear Factor kappa B (NF-κB) pathway activation and the production of pro-inflammatory cytokines (such as interleukin-1, interleukin-6 and interferon β) that increase inflammation-related damage, chemokines (such as MCP-1) and adhesion molecules [85,86]. In this context, the release of pro-inflammatory cytokines result in endothelial cell dysfunction, inducing coagulation cascade activation and leukocyte recruitment [87].…”

The Role of Bioactives in Inflammation

“…A mortality rate of up to 40% is associated with acute kidney injury (AKI) caused by sepsis. Several mechanisms are involved in the pathogenesis of septic AKI, which lead to an increase in inflammation and renal dysfunction [ 8 ]. Inflammatory disorders can be treated with eupatilin (EUP), which is a natural flavone that exerts multiple biological activities.…”