2021
DOI: 10.1097/mnh.0000000000000716
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Endothelin receptor antagonists for the treatment of diabetic and nondiabetic chronic kidney disease

Abstract: Purpose of reviewTo summarize new clinical findings of endothelin receptor antagonists (ERA) in various etiologies of kidney disease targeted in clinical trials. Recent findingsEndothelin-1 is a multifunctional peptide with potential relevance to glomerular and tubulointerstitial kidney diseases. The phase 3 SONAR trial demonstrated a significant reduction in clinically relevant kidney outcomes for patients with diabetic kidney disease (DKD) after long-term treatment with the ERA, atrasentan, in addition to bl… Show more

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Cited by 26 publications
(13 citation statements)
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“…This gap has been the driving force of hypertension research agenda to explore alternative therapeutic approaches and to improve the effectiveness of current drugs. Therefore, several preclinical and clinical studies in different stages are ongoing and aim to test novel agents like ACE2/Ang (1-7)/MasR axis activators, 141 endothelin antagonists, 142,143 aldosterone-synthase inhibitors, 144 dual inhibitors of neprilysin, soluble guanyl cyclase A stimulators, dual activating bispecific peptides (ie, peptides, which mimic the action of an endogenous peptide, acting on 2 separate signaling pathways), antioxidants, and aminopeptidase inhibitors. 141 In the future, these prominent therapies might prove to be safe and efficient not only for lowering BP but also for preventing target end-organ damage, especially for patients with high cardiovascular burden like patients with CKD.…”
Section: Compendium On Increased Risk Of Cardiovascular Complications...mentioning
confidence: 99%
“…This gap has been the driving force of hypertension research agenda to explore alternative therapeutic approaches and to improve the effectiveness of current drugs. Therefore, several preclinical and clinical studies in different stages are ongoing and aim to test novel agents like ACE2/Ang (1-7)/MasR axis activators, 141 endothelin antagonists, 142,143 aldosterone-synthase inhibitors, 144 dual inhibitors of neprilysin, soluble guanyl cyclase A stimulators, dual activating bispecific peptides (ie, peptides, which mimic the action of an endogenous peptide, acting on 2 separate signaling pathways), antioxidants, and aminopeptidase inhibitors. 141 In the future, these prominent therapies might prove to be safe and efficient not only for lowering BP but also for preventing target end-organ damage, especially for patients with high cardiovascular burden like patients with CKD.…”
Section: Compendium On Increased Risk Of Cardiovascular Complications...mentioning
confidence: 99%
“…Our first conclusion is that the ET system via activation of ET A importantly contributes to the progression of CHF coexisting with CKD. Very probably, selective inhibition of ET A receptor mediated the beneficial actions by: (i) preventing direct vasoconstrictor actions of ET-1, (ii) preventing ET-1 induced glomerular large-pore hyperpermeability and glomerular barrier (podocyte) damage, (iii) unmasking ET B receptormediated vasodilatory and natriuretic actions of ET-1, in the light of the current knowledge about the pathobiology of ET-1 in the kidney [18][19][20]53]. Remarkably, previous studies using less selective ET A blockade failed to improve the course of CHF and CKD.…”
Section: Discussionmentioning
confidence: 99%
“…Nevertheless, the combined treatment displayed marked additional beneficial actions on albuminuria and important renoprotective effects, such as alleviation of the renal glomerular and cortical tubulointerstitial injury. Increased albuminuria is a strong and independent predictor for all-cause mortality in CKD as well as in CHF [3][4][5]7,8,53,55], hence with the prolonged treatment the additive beneficial actions on the course of CKD-and CHF-related mortality could occur. Such reasoning is supported by the favourable actions on renal glomerular and tubulointerstitial morphology: 5/6 + ACF HanSD rats treated within the late treatment protocol with either ET A antagonist alone or ACEi alone showed marked renal glomerular damage, similar as observed in untreated animals.…”
Section: Discussionmentioning
confidence: 99%
“…Two blockers of the endothelin-system are currently undergoing clinical testing in phase III trials in patients with IgAN: sparsentan, a dual blocker of the angiotensin-II and endothelin-A receptor, in the PROTECT trial (ClinicalTrials.gov Identifier: NCT04663204) as well as atrasentan, a selective blocker of the endothelin-A receptor, in the ALIGN trial (NCT04573478) [13]. First interim results from the PROTECT trial indicate an about 50% proteinuria reduction after 36 weeks with good safety [14].…”
Section: Supportive Therapymentioning
confidence: 99%