Mineralocorticoid receptor antagonists in diabetic kidney disease — mechanistic and therapeutic effects

2021 ◽  
Author(s):  
Jonatan Barrera-Chimal ◽  
Ixchel Lima-Posada ◽  
George L. Bakris ◽  
Frederic Jaisser
Keyword(s):  
Kidney Disease ◽  
Mineralocorticoid Receptor ◽  
Diabetic Kidney Disease ◽  
Therapeutic Effects ◽  
Mineralocorticoid Receptor Antagonists ◽  
Receptor Antagonists ◽  
Diabetic Kidney

scholarly journals Mineralocorticoid receptor antagonists for nephroprotection and cardioprotection in patients with diabetes mellitus and chronic kidney disease

2021 ◽  
Author(s):  
Alberto Ortiz ◽  
Charles J Ferro ◽  
Olga Balafa ◽  
Michel Burnier ◽  
Robert Ekart ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Failure ◽  
Mineralocorticoid Receptor ◽  
Diabetic Kidney Disease ◽  
Renin Angiotensin System ◽  
Cardiovascular Death ◽  
Mineralocorticoid Receptor Antagonists ◽  
Receptor Antagonists ◽  
Diabetic Kidney

Abstract Diabetic kidney disease develops in about 40% of patients with diabetes and is the commonest cause of chronic kidney disease worldwide. Patients with chronic kidney disease, especially those with diabetes mellitus, are at high risk of both developing kidney failure and cardiovascular death. The use of renin-angiotensin system blockers to reduce the incidence of kidney failure in patients with diabetic kidney disease dates back to studies that are now 20 or more years old. During the last few years sodium-glucose co-transporter-2 inhibitors have shown beneficial renal effects in randomized trials. However, even in response to combined treatment with renin-angiotensin system blockers and sodium-glucose co-transporter-2 inhibitors, the renal residual risk remains high with kidney failure only deferred, but not avoided. The risk of cardiovascular death also remains high even with optimal current treatment. Steroidal mineralocorticoid receptor antagonists reduce albuminuria and surrogate markers of cardiovascular disease in patients already on optimal therapy. However, their use has been curtailed by the significant risk of hyperkalaemia. In The FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease (FIDELIO-DKD) study comparing the actions of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo, finerenone reduced the progression of diabetic kidney disease and the incidence of cardiovascular events with a relatively safe adverse event profile. This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of mineralocorticoid receptor antagonists, analyses the potential mechanisms involved and discusses their potential future place in the treatment of patients with diabetic chronic kidney disease.

scholarly journals Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease

2021 ◽  
Vol 14 (6) ◽  
pp. 561
Author(s):  
Nina Vodošek Vodošek Hojs ◽  
Sebastjan Bevc ◽  
Robert Ekart ◽  
Nejc Piko ◽  
Tadej Petreski ◽  
...  
Keyword(s):  
Side Effects ◽  
Kidney Disease ◽  
Mineralocorticoid Receptor ◽  
Diabetic Kidney Disease ◽  
Extracellular Fluid ◽  
Diabetic Patients ◽  
Mineralocorticoid Receptor Antagonists ◽  
Receptor Antagonists ◽  
Diabetic Kidney ◽  
Cardiovascular Morbidity And Mortality

Diabetes mellitus is a global health issue and main cause of chronic kidney disease. Both diseases are also linked through high cardiovascular morbidity and mortality. Diabetic kidney disease (DKD) is present in up to 40% of diabetic patients; therefore, prevention and treatment of DKD are of utmost importance. Much research has been dedicated to the optimization of DKD treatment. In the last few years, mineralocorticoid receptor antagonists (MRA) have experienced a renaissance in this field with the development of non-steroidal MRA. Steroidal MRA have known cardiorenal benefits, but their use is limited by side effects, especially hyperkalemia. Non-steroidal MRA still block the damaging effects of mineralocorticoid receptor overactivation (extracellular fluid volume expansion, inflammation, fibrosis), but with fewer side effects (hormonal, hyperkalemia) than steroidal MRA. This review article summarizes the current knowledge and newer research conducted on MRA in DKD.

scholarly journals Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Daiji Kawanami ◽  
Yuichi Takashi ◽  
Yoshimi Muta ◽  
Naoki Oda ◽  
Dai Nagata ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Mineralocorticoid Receptor ◽  
Diabetic Kidney Disease ◽  
Current Knowledge ◽  
Mineralocorticoid Receptor Antagonists ◽  
Future Perspectives ◽  
End Stage Kidney Disease ◽  
Diabetic Kidney ◽  
Fibrotic Process ◽  
End Stage

Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease (ESKD) worldwide. Mineralocorticoid receptor (MR) plays an important role in the development of DKD. A series of preclinical studies revealed that MR is overactivated under diabetic conditions, resulting in promoting inflammatory and fibrotic process in the kidney. Clinical studies demonstrated the usefulness of MR antagonists (MRAs), such as spironolactone and eplerenone, on DKD. However, concerns regarding their selectivity for MR and hyperkalemia have remained for these steroidal MRAs. Recently, nonsteroidal MRAs, including finerenone, have been developed. These agents are highly selective and have potent anti-inflammatory and anti-fibrotic properties with a low risk of hyperkalemia. We herein review the current knowledge and future perspectives of MRAs in DKD treatment.

Cardiovascular Protection With Sodium-Glucose Cotransporter-2 Inhibitors and Mineralocorticoid Receptor Antagonists in Chronic Kidney Disease

Hypertension ◽  
2021 ◽  
Vol 77 (5) ◽  
pp. 1442-1455
Author(s):  
Pantelis Sarafidis ◽  
Christodoulos E. Papadopoulos ◽  
Vasilios Kamperidis ◽  
George Giannakoulas ◽  
Michael Doumas
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiovascular Events ◽  
Mineralocorticoid Receptor ◽  
Mineralocorticoid Receptor Antagonists ◽  
Receptor Antagonists ◽  
Cardiovascular Protection ◽  
Sodium Glucose Cotransporter

Chronic kidney disease (CKD) and cardiovascular disease are intimately linked. They share major risk factors, including age, hypertension, and diabetes, and common pathogenetic mechanisms. Furthermore, reduced renal function and kidney injury documented with albuminuria are independent risk factors for cardiovascular events and mortality. In major renal outcome trials and subsequent meta-analyses in patients with CKD, ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin II receptor blockers) were shown to effectively retard CKD progression but not to significantly reduce cardiovascular events or mortality. Thus, a high residual risk for cardiovascular disease progression under standard-of-care treatment is still present for patients with CKD. In contrast to the above, several outcome trials with SGLT-2 (sodium-glucose cotransporter-2) inhibitors and MRAs (mineralocorticoid receptor antagonists) clearly suggest that these agents, apart from nephroprotection, offer important cardioprotection in this population. This article discusses existing evidence on the effects of SGLT-2 inhibitors and MRAs on cardiovascular outcomes in patients with CKD that open new roads in cardiovascular protection of this heavily burdened population.

scholarly journals Gynostemma Pentaphyllum Ameliorates Lipid Metabolic Abnormalities in Diabetic Kidney Disease

2022 ◽  
Author(s):  
Pengrui Wang ◽  
Shouhai Jiao ◽  
Li Sun ◽  
Helin Sun ◽  
Cunzhi Wang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Enrichment Analysis ◽  
Underlying Mechanism ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Protective Mechanisms ◽  
Diabetic Kidney ◽  
Gynostemma Pentaphyllum ◽  
Protein Protein Interaction

Abstract Background: Patients with diabetic kidney disease (DKD) were often accompanied with dislipidemia. Gynostemma pentaphyllum can ameliorate insulin resistance and reduce the synthesis of triglycerides and cholesterol, but the underlying mechanism is still unclear. Therefore, we used the network pharmacologic strategies to evaluate potential therapeutic effects and protective mechanisms of gynostemma pentaphyllum on diabetic kidney disease. Methods: Gynostemma pentaphyllum's potential targets were predicted using the TCMSP databases. The pathogenic factors involved in DKD and dislipidemia were screened by the OMIM and Gene Cards databases. The common targets of gynostemma pentaphyllum, DKD and dislipidemia were used to establish a protein-protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to explore the potential molecular pathways. Results: The key targets for the therapeutic effects of gynostemma pentaphyllum included IL-6, AKT1, VEGFA, PTGS2, CCL2 and CASP3. Enrichment analysis showed that the underlying mechanism were mainly the involved in inhibition of inflammatory response, negative regulation of apoptotic process and angiogenesis. TNF, PI3K-Akt, and HIF-1 signaling pathways were considered as the key pathways. Conclusion: Gynostemma pentaphyllum played a therapeutic role in DKD complicated with dislipidemia, mainly through influencing inflammation response, apoptosis and angiogenesis.

Local Mineralocorticoid Receptor Activation and the Role of Rac1 in Obesity-Related Diabetic Kidney Disease

2014 ◽  
Vol 126 (1) ◽  
pp. 16-24 ◽  
Author(s):  
Shigetaka Yoshida ◽  
Kenichi Ishizawa ◽  
Nobuhiro Ayuzawa ◽  
Kohei Ueda ◽  
Maki Takeuchi ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Mineralocorticoid Receptor ◽  
Diabetic Kidney Disease ◽  
Receptor Activation ◽  
Diabetic Kidney
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