Acute kidney injury (AKI) is a complex syndrome that occurs in critically ill patients and has different etiologies and extremely variable pathogenesis. Despite relevant therapeutic advances, AKI still remains associated with unacceptably high mortality risk. The sudden decrease in renal function can be secondary to a heterogeneous spectrum of conditions such as sepsis, renal ischemia reperfusion (I/R) injury, nephrotoxin exposition or major surgery.
A growing body of evidence has demonstrated that the immune system is strongly involved in mediating injury to renal endothelial, tubular and perivascular cells, suggesting an underestimated role of strategies targeting the immune system to counteract AKI. Specialized systemic immune cell populations as dendritic cells (DCs), neutrophils, T lymphocytes, monocytes/macrophages and B lymphocytes as well as local immune cells in the kidney (such as DCs) can exacerbate the kidney injury, leading to transition from AKI to Chronic Kidney Disease (CKD) and to long-term renal deterioration consequences as fibrosis. Both the innate and adaptive immune systems are essential for eliminating microbial pathogens and repairing tissue after injury; however, in the AKI, the aberrant innate immune activation of DCs, neutrophils and M1 macrophages has been identified as the leading cause of renal dysfunction. In contrast, other immune cell subpopulations as M2 macrophages and regulatory T cells (Treg) have been emerged to extinguish inflammation, thereby promoting tissue repair and to decelerate the progression to CKD.
Moreover, besides immune cells, soluble components of innate immunity such as complement system play a central role in the pathophysiology of I/R injury. Furthermore, kidney cells can release almost all complement proteins, therefore amplifying the complement activation in the kidney that has a unique susceptibility to complement-mediated damage. The interest in the complement system is growing given the fact that there is an increasing number of clinical trials aimed to evaluate the potential of new complement inhibitors in the prevention of transplant induced-AKI. In addition, extracellular vesicles (EV), small particles derived from the endosomal compartment, represent a new mechanism of cell-to-cell communication through the transfer of RNA and proteins. EVs are present in the plasma of normal subjects, however, their involvement as mediators of sepsis-induced AKI is not well understood.
We welcome the submission of Original Research articles, Reviews, and Commentaries describing the role of all the possible pivotal players in the immune-mediated AKI pathophysiology such as systemic and resident immune cells, complement, and coagulation system, extracellular vesicles (EVs), RNAs (as miRNA, lnRNA, mRNA) or novel discovered proteins.
Understanding the molecular mechanisms by which the immune system could counteract or accelerate AKI may offer new insight into therapeutic opportunities in the AKI population in order to improve outcomes and life quality.
Acute kidney injury (AKI) is a complex syndrome that occurs in critically ill patients and has different etiologies and extremely variable pathogenesis. Despite relevant therapeutic advances, AKI still remains associated with unacceptably high mortality risk. The sudden decrease in renal function can be secondary to a heterogeneous spectrum of conditions such as sepsis, renal ischemia reperfusion (I/R) injury, nephrotoxin exposition or major surgery.
A growing body of evidence has demonstrated that the immune system is strongly involved in mediating injury to renal endothelial, tubular and perivascular cells, suggesting an underestimated role of strategies targeting the immune system to counteract AKI. Specialized systemic immune cell populations as dendritic cells (DCs), neutrophils, T lymphocytes, monocytes/macrophages and B lymphocytes as well as local immune cells in the kidney (such as DCs) can exacerbate the kidney injury, leading to transition from AKI to Chronic Kidney Disease (CKD) and to long-term renal deterioration consequences as fibrosis. Both the innate and adaptive immune systems are essential for eliminating microbial pathogens and repairing tissue after injury; however, in the AKI, the aberrant innate immune activation of DCs, neutrophils and M1 macrophages has been identified as the leading cause of renal dysfunction. In contrast, other immune cell subpopulations as M2 macrophages and regulatory T cells (Treg) have been emerged to extinguish inflammation, thereby promoting tissue repair and to decelerate the progression to CKD.
Moreover, besides immune cells, soluble components of innate immunity such as complement system play a central role in the pathophysiology of I/R injury. Furthermore, kidney cells can release almost all complement proteins, therefore amplifying the complement activation in the kidney that has a unique susceptibility to complement-mediated damage. The interest in the complement system is growing given the fact that there is an increasing number of clinical trials aimed to evaluate the potential of new complement inhibitors in the prevention of transplant induced-AKI. In addition, extracellular vesicles (EV), small particles derived from the endosomal compartment, represent a new mechanism of cell-to-cell communication through the transfer of RNA and proteins. EVs are present in the plasma of normal subjects, however, their involvement as mediators of sepsis-induced AKI is not well understood.
We welcome the submission of Original Research articles, Reviews, and Commentaries describing the role of all the possible pivotal players in the immune-mediated AKI pathophysiology such as systemic and resident immune cells, complement, and coagulation system, extracellular vesicles (EVs), RNAs (as miRNA, lnRNA, mRNA) or novel discovered proteins.
Understanding the molecular mechanisms by which the immune system could counteract or accelerate AKI may offer new insight into therapeutic opportunities in the AKI population in order to improve outcomes and life quality.
