Renin Angiotensin System and Cytokines in Chronic Kidney Disease: Clinical and Experimental Evidence.

Abstract

Chronic kidney disease (CKD) has been considered an important public health issue in all countries. Experimental and clinical studies support the general idea that the pathophysiology of CKD is associated with the interaction of several endogenous mediators, including components of the renin-angiotensin system (RAS) and cytokines. This review aims to report available evidence on the interaction of RAS molecules and cytokines in CKD. Therapeutic administration of angiotensin converting enzyme (ACE) inhibitors and/or angiotensin type 1 (AT1) receptor antagonists can slow down the deterioration of renal function. These medications reduce the formation (ACE inhibitor) or the receptor-mediated effects of Angiotensin II (AT1 antagonist) and by so doing inhibit cytokine-mediated kidney tissue inflammation. In sharp contrast, the activation of ACE2, the stimulation of Angiotensin-(1-7) synthesis and/or the effects mediated by its G-protein coupled receptor, named Mas receptor, ameliorates experimental renal injury by reducing renal tissue inflammation and fibrosis in many experimental models of renal diseases. Novel compounds that activate and/or stimulate ACE2-Angiontensin-(1-7)-Mas receptor axis may also play a role in the treatment of CKD, mainly by controlling inflammatory response and pathways of fibrosis at kidney tissue. Clinical trials with these new pharmacological compounds will, in due course, determine whether this promise will become a helpful treatment.