Immunomodulatory Approaches in Diabetes-Induced Cardiorenal Syndromes

Abstract

Immunomodulatory approaches are defined as all interventions that modulate and curb the immune response of the host rather than targeting the disease itself with the aim of disease prevention or treatment. A better understanding of the immune system continues to offer innovative drug targets and methods for immunomodulatory interventions. Cardiorenal syndrome is a clinical condition that defines disorders of the heart and kidneys, both of which communicate with one another through multiple pathways in an interdependent relationship. Cardiorenal syndrome denotes the confluence of heart-kidney relationships across numerous interfaces. As such, a dysfunctional heart or kidney has the capacity to initiate disease in the other organ via common hemodynamic, neurohormonal, immunological, and/or biochemical feedback pathways. Understanding how immunomodulatory approaches are implemented in diabetes-induced cardiovascular and renal diseases is important for a promising regenerative medicine, which is the process of replacing cells, tissues or organs to establish normal function. In this article, after a brief introduction on the immunomodulatory approaches in diseases, we will be reviewing the epidemiology and classifications of cardiorenal syndrome. We will be emphasizing on the hemodynamic factors and non-hemodynamic factors linking the heart and the kidneys. In addition, we will be elaborating on the immunomodulatory pathways involved in diabetes-induced cardiorenal syndrome namely, RAS, JAK/STAT, and oxidative stress. Moreover, we will be addressing possible therapeutic approaches that target the former pathways in an attempt to modulate the immune system.

Keywords: JAK/STAT pathway; cardiorenal syndromes; diabetes mellitus; immunomodulatory approaches; oxidative stress; ras pathway.

Figure 1

Different conditions such as Sepsis, diabetes, hypertension, ROS, and inflammation cause damage to the kidney or heart where one organ has the ability to injure the other organ by the means of hemodynamic and non-hemodynamic factors linking the heart and the kidneys.

Figure 2

RAS pathway in leading kidney failure. Renin acts on Angiotensinogen secreted by the liver, transforming it to Angiotensin I, which will then be transformed into Angiotensin II via ACE.

Figure 3

Angiotensin II signaling pathways. Angiotensin II induces inflammatory cytokine production via binding to AT-1 and AT-2.

Figure 4

Representing scheme of clinical link between diabetes mellitus, cardiovascular disease, and chronic kidney disease.