Abstract
Purpose of review Despite optimal therapy of diabetic nephropathy with agents blocking the renin-angiotensin-aldosterone system, the residual risk of nephropathy progression to end-stage renal disease (ESRD) remains high. The purpose of this review is to discuss the potential role of endothelin antagonism as a therapeutic tool to reduce residual proteinuria and delay kidney injury progression among patients with diabetic nephropathy. Recent findings Preclinical studies have shown that endothelin receptor antagonists (ERAs) exert proteinuria lowering and nephroprotective actions in experimental models of diabetic nephropathy. ERAs reduce proteinuria in phase 2 trials that included therapy with renin-angiotensin-aldosterone system blockers. Safety of these agents and protection from ESRD needs to be demonstrated in phase 3 trials. Excess risk of fluid retention and heart failure risk remains. Summary The hypothesis that the antiproteinuric effect of endothelin antagonism may be translated into a slower progression of diabetic nephropathy to ESRD is investigated in ongoing randomized trials assessing 'hard' renal endpoints. ERAs may represent a promising tool toward renoprotection in diabetic nephropathy by individualizing therapy and mitigating the risk of heart failure, if these trials are positive.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 338-344 |
| Number of pages | 7 |
| Journal | Current Opinion in Nephrology and Hypertension |
| Volume | 26 |
| Issue number | 5 |
| DOIs | |
| State | Published - Sep 1 2017 |
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Keywords
- diabetic nephropathy
- endothelin antagonism
- kidney injury progression
- proteinuria
ASJC Scopus subject areas
- Internal Medicine
- Nephrology
Cite this
Endothelin A receptor antagonists in diabetic kidney disease. / Georgianos, Panagiotis I.; Agarwal, Rajiv.
In: Current Opinion in Nephrology and Hypertension, Vol. 26, No. 5, 01.09.2017, p. 338-344.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Endothelin A receptor antagonists in diabetic kidney disease
AU - Georgianos, Panagiotis I.
AU - Agarwal, Rajiv
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Purpose of review Despite optimal therapy of diabetic nephropathy with agents blocking the renin-angiotensin-aldosterone system, the residual risk of nephropathy progression to end-stage renal disease (ESRD) remains high. The purpose of this review is to discuss the potential role of endothelin antagonism as a therapeutic tool to reduce residual proteinuria and delay kidney injury progression among patients with diabetic nephropathy. Recent findings Preclinical studies have shown that endothelin receptor antagonists (ERAs) exert proteinuria lowering and nephroprotective actions in experimental models of diabetic nephropathy. ERAs reduce proteinuria in phase 2 trials that included therapy with renin-angiotensin-aldosterone system blockers. Safety of these agents and protection from ESRD needs to be demonstrated in phase 3 trials. Excess risk of fluid retention and heart failure risk remains. Summary The hypothesis that the antiproteinuric effect of endothelin antagonism may be translated into a slower progression of diabetic nephropathy to ESRD is investigated in ongoing randomized trials assessing 'hard' renal endpoints. ERAs may represent a promising tool toward renoprotection in diabetic nephropathy by individualizing therapy and mitigating the risk of heart failure, if these trials are positive.
AB - Purpose of review Despite optimal therapy of diabetic nephropathy with agents blocking the renin-angiotensin-aldosterone system, the residual risk of nephropathy progression to end-stage renal disease (ESRD) remains high. The purpose of this review is to discuss the potential role of endothelin antagonism as a therapeutic tool to reduce residual proteinuria and delay kidney injury progression among patients with diabetic nephropathy. Recent findings Preclinical studies have shown that endothelin receptor antagonists (ERAs) exert proteinuria lowering and nephroprotective actions in experimental models of diabetic nephropathy. ERAs reduce proteinuria in phase 2 trials that included therapy with renin-angiotensin-aldosterone system blockers. Safety of these agents and protection from ESRD needs to be demonstrated in phase 3 trials. Excess risk of fluid retention and heart failure risk remains. Summary The hypothesis that the antiproteinuric effect of endothelin antagonism may be translated into a slower progression of diabetic nephropathy to ESRD is investigated in ongoing randomized trials assessing 'hard' renal endpoints. ERAs may represent a promising tool toward renoprotection in diabetic nephropathy by individualizing therapy and mitigating the risk of heart failure, if these trials are positive.
KW - diabetic nephropathy
KW - endothelin antagonism
KW - kidney injury progression
KW - proteinuria
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U2 - 10.1097/MNH.0000000000000342
DO - 10.1097/MNH.0000000000000342
M3 - Review article
VL - 26
SP - 338
EP - 344
JO - Current Opinion in Nephrology and Hypertension
JF - Current Opinion in Nephrology and Hypertension
SN - 1062-4821
IS - 5
ER -