Inhibition of RAS in diabetic nephropathy.
Diabetic kidney disease (DKD) is a progressive proteinuric renal disorder in patients with type 1 or type 2 diabetes mellitus. It is a common cause of end-stage kidney disease worldwide, particularly in developed countries. Therapeutic targeting of the renin-angiotensin system (RAS) is the most validated clinical strategy for slowing disease progression. DKD is paradoxically a low systematic renin state with an increased intrarenal RAS activity implicated in its pathogenesis. Angiotensin II (AngII), the main peptide of RAS, is not only a vasoactive peptide but functions as a growth factor, activating interstitial fibroblasts and mesangial and tubular cells, while promoting the synthesis of extracellular matrix proteins. AngII also promotes podocyte injury through increased calcium influx and the generation of reactive oxygen species. Blockade of the RAS using either angiotensin converting enzyme inhibitors, or angiotensin receptor blockers can attenuate progressive glomerulosclerosis in animal models, and slows disease progression in humans with DKD. In this review, we summarize the role of intrarenal RAS activation in the pathogenesis and progression of DKD and the rationale for RAS inhibition in this population.
Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Rabi
R
Yacoub
Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Kirk N
KN
Campbell
angiotensin II; angiotensin receptor blockers; angiotensin-converting enzyme inhibitors; diabetic kidney disease; renin-angiotensin system