The role of the renal kallikrein-kinin system in diabetic nephropathy.
OBJECTIVE
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.


RESULTS
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 long-acting bradykinin B2 receptor agonists have been shown to have renal protective effects, their therapeutic benefits have not been well studied.


CONCLUSIONS
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.
Riad
Alexander
A
Charité University Medicine Berlin, Department of Cardiology, Berlin, Germany.
Zhuo
Jia Long
JL
Schultheiss
Heinz Peter
HP
Tschöpe
Carsten
C
D000818:Animals; D001920:Bradykinin / Q000819:agonists; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology*; D006575:Heterocyclic Compounds, 3-Ring / Q000627:therapeutic use; D006801:Humans; D016234:Kallikrein-Kinin System / Q000187:drug effects / Q000502:physiology*; D007668:Kidney / Q000201:enzymology*; D011480:Protease Inhibitors / Q000627:therapeutic use; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology
C479877:AVE 7688; D006575:Heterocyclic Compounds, 3-Ring; D011480:Protease Inhibitors; D001920:Bradykinin