The kallikrein-kinin system in diabetic nephropathy.
Authors Tomita H, Sanford RB, Smithies O, Kakoki M
Submitted By Oliver Smithies on 8/1/2012
Status Published
Journal Kidney international
Year 2012
Date Published 4/1/2012
Volume : Pages 81 : 733 - 744
PubMed Reference 22318421
Abstract Diabetic nephropathy is the major cause of end-stage renal disease worldwide.
Although the renin-angiotensin system has been implicated in the pathogenesis of
diabetic nephropathy, angiotensin I-converting enzyme inhibitors have a
beneficial effect on diabetic nephropathy independently of their effects on
blood pressure and plasma angiotensin II levels. This suggests that the
kallikrein-kinin system (KKS) is also involved in the disease. To study the role
of the KKS in diabetic nephropathy, mice lacking either the bradykinin B1
receptor (B1R) or the bradykinin B2 receptor (B2R) have been commonly used.
However, because absence of either receptor causes enhanced expression of the
other, it is difficult to determine the precise functions of each receptor. This
difficulty has recently been overcome by comparing mice lacking both receptors
with mice lacking each receptor. Deletion of both B1R and B2R reduces nitric
oxide (NO) production and aggravates renal diabetic phenotypes, relevant to
either lack of B1R or B2R, demonstrating that both B1R and B2R exert protective
effects on diabetic nephropathy presumably via NO. Here, we review previous
epidemiological and experimental studies, and discuss novel insights regarding
the therapeutic implications of the importance of the KKS in averting diabetic
nephropathy.


Investigators with authorship
NameInstitution
Oliver SmithiesUniversity of North Carolina

Complications