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2012 ; 5
(1
): 17-27
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Endothelin and the podocyte
#MMPMID26069741
Barton M
; Tharaux PL
Clin Kidney J
2012[Feb]; 5
(1
): 17-27
PMID26069741
show ga
In the past decade, research has advanced our understanding how endothelin
contributes to proteinuria and glomerulosclerosis. Data from pre-clinical and
clinical studies now provide evidence that proteinuric diseases such as focal
segmental glomerulosclerosis and diabetic nephropathy as well as hypertension
nephropathy are sensitive to treatment with endothelin receptor antagonists
(ERAs). Like blockade of the renin-angiotensin system, ERA treatment-under
certain conditions-may even cause disease regression, effects that could be
achieved on top of renin-angiotensin-aldosterone system blockade, suggesting
independent therapeutic mechanisms by which ERAs convey nephroprotection.
Beneficial effects of ERAs on podocyte function, which is essential to maintain
the glomerular filtration barrier, have been identified as one of the key
mechanisms by which inhibition of the endothelin ETA receptor ameliorates renal
structure and function. In this article, we will review pre-clinical studies
demonstrating a causal role for endothelin in proteinuric chronic kidney disease
(with a particular focus on functional and structural integrity of podocytes in
vitro and in vivo). We will also review the evidence suggesting a therapeutic
benefit of ERA treatment on the functional integrity of podocytes in humans.
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