Innovative Biologics and Drugs to Target Renal Inflammation

About this Research Topic

Background

Acute kidney injury (AKI), chronic kidney disease (CKD) and end-stage renal disease (ESRD) represent global health challenges that exert profound negative effects on the quality and quantity of life of those afflicted and account for a disproportionately high amount of the total healthcare costs in many countries. Furthermore, as a result of population aging, the rising incidence of chronic non-communicable conditions such as obesity, diabetes and hypertension and the increasing complexity of hospital care, the numbers of people affected by AKI and CKD/ESRD are increasing worldwide. Epidemiological, clinical and pre-clinical research over the past two decades has revealed that acute and chronic loss of kidney function are associated with remarkable increases in the risk for death and cardiovascular events compared to preserved kidney function. More recent lines of investigation have also demonstrated that single or multiple episodes of AKI frequently transition over time to CKD and are beginning to identify distinct pathophysiological pathways that contribute to this association. These epidemiological trends and recent clinical and pathological insights have highlighted the urgent need for new and more specific therapies to target kidney disease.

One important area of research that links AKI, CKD, ESRD and their life-limiting complications is the participation of inflammation and elements of the immune system in virtually all forms of renal and cardiovascular disease. Specifically, local and system mediators of inflammatory response are now known to be triggered by cell stress pathway or cell death mechanisms within the kidney as well as by endogenous and exogenous molecular mediators (“uremic toxins”) that begin to accumulate as renal function declines. Secondarily, dysregulated innate and adaptive immune cells play active roles in the progression of renal interstitial fibrosis, in distant organ injury during AKI and in the acceleration of atherosclerosis, arteriosclerosis and vascular calcification in CKD/ESRD.

The past two decades have seen dramatic increases in knowledge of renal-resident immune cell populations and in kidney-specific immune response/inflammation in the context of acute and chronic injury or disease. Furthermore, exciting developments in biologics and drugs to modulate inflammation and immune response in other fields such as cancer, autoimmunity and transplantation is beginning to impact the field kidney disease. Specifically, innovative research programs in academic and industry settings now seek to target a wide range of immune/inflammatory, pro-fibrotic and pro-atherogenic pathways in the setting of AKI and CKD using repurposed or emerging drugs and novel agents such as peptidometics, small interfering- or micro-RNAs, monoclonal/chimeric antibodies and recombinant proteins. A small number of recent clinical trials have also provided encouraging early phase evidence for the potential of inflammation-targeting drugs and biologics to ameliorate the severity or progression of kidney disease.

This Research Topic will highlight recent basic, pre-clinical and clinical progress and opportunities related to the targeting of renal inflammation using drugs and biologic agents by publishing relevant full length and short original research communications as well as opinion and review articles.

Keywords: Kidney, Inflammation, Biologics, Peptides, Small interfering RNA

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