The role of the renal kallikrein–kinin system in diabetic nephropathy

Abstract

Purpose of review-Diabetic nephropathy is one of the most common complications in diabetes mellitus. Multiple pathogenic mechanisms are now believed to contribute to this disease, including inflammatory cytokines, autacoids and oxidative stress. Numerous studies have shown that the kallikrein-kinin system may be involved in these mechanisms. This review focuses on recent research advance on the potential role of the kallikrein-kinin system in the development of diabetic nephropathy, and its clinical relevance.Recent findings-A collection of recent studies has shown that angiotensin-converting enzyme inhibitors, which inhibit angiotensin II formation and degradation of bradykinin, and vasopeptidase inhibitors attenuated the development of diabetic nephropathy in experimental animals and clinical settings. The role of the kallikrein-kinin system in diabetes is further supported by findings that diabetic nephropathy is worsened in diabetic mice lacking bradykinin B2 receptors. Although longacting bradykinin B2 receptor agonists have been shown to have renal protective effects, their therapeutic benefits have not been well studied.Summary-Current experimental investigations demonstrated that pharmacological intervention of the kallikrein-kinin system improved renal conditions in diabetes mellitus. These findings suggest that the kallikrein-kinin system may be a therapeutic target in preventing and treating diabetic nephropathy.

The high glucose-induced stimulation of B1R and B2R expression via CB1R activation is involved in rat podocyte apoptosis

“…The kallikrein-kinin system (KKS) can be divided into two components: circulating and tissue/renal KKS (Riad et al, 2007;Bhoola et al, 1992). Bradykinin (BK), a major KKS effector, is a nonapeptide with a wide range of activities.…”

Bradykinin acutely inhibits activity of the epithelial Na+channel in mammalian aldosterone-sensitive distal nephron

“…Specifically, kallikrein is actively synthesized in the CNT, whereas kininogen and B2 receptors are expressed mainly in the collecting duct (59). Stimulation of the renal KKS results in diuresis and natriuresis (49). Mice lacking receptors for BK develop salt-sensitive hypertension (1,2).…”

The cardiovascular influence of interleukin-1β on the expression of bradykinin B1 and B2 receptors

“…Kinins mediate their effects mainly via two receptors, namely the bradykinin 1 receptor (B1R) and the bradykinin 2 receptor (B2R) [1]. We have described previously that both receptors are upregulated after myocardial ischemia [2].…”