Efficacy and safety of finerenone in patients with chronic kidney disease and type 2 diabetes by <scp>GLP‐1RA</scp> treatment: A subgroup analysis from the <scp>FIDELIO‐DKD</scp> trial

Rossing, Peter; Agarwal, Rajiv; Anker, Stefan D.; Filippatos, Gerasimos; Pitt, Bertram; Ruilope, Luis; Amod, Aslam; Marre, Michel; Joseph, Amer; Lage, Andrea; Scott, Charlie; Bakris, George L.

doi:10.1111/dom.14558

Cited by 49 publications

(26 citation statements)

References 36 publications

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“…Similarly, hypoglycemic agents such as metformin and GLP‐1 receptor agonists are used to maintain normoglycemic index. Additionally, lipid‐lowering drugs and agents such as finerenone are being used to prevent renal tissue scaring due to uncontrolled blood glucose (Fineberg et al, 2013; Rossing et al, 2022) Thus, it is necessary to develop effective and precise therapeutic strategies for DN (Selby & Taal, 2020). As several factors attribute to renal injury in DN, hyperglycaemia‐induced metabolic load and subsequent activation of pathways that are responsible for redox imbalance is a widely accepted mechanism in DN (Dronavalli et al, 2008, Sagoo & Gnudi, 2018; Sherkhane et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Melatonin prevents diabetes‐induced nephropathy by modulating the AMPK/SIRT1 axis: Focus on autophagy and mitochondrial dysfunction

Jain

Sherkhane

Kalavala

et al. 2022

Cell Biology International

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Impaired nutrient sensing mechanisms such as AMPK/silent information regulator type 1 (SIRT1) axis and autophagy in renal cells upon chronic diabetic condition accelerate renal injury and upregulating these mechanisms has been reported to prevent renal damage. Melatonin, a neuroendocrine agent, also possess antioxidant and AMPK modulatory effect. In the current study, the protective effect of melatonin against diabetic renal injury was assessed in streptozotocin‐induced diabetic nephropathy model and in in vitro model of high‐glucose‐induced tubular injury. Melatonin (3 and 10 mg/kg) was administered for 28 days after 4 weeks of diabetes induction in Sprague–Dawley rats. For in vitro model, the NRK‐52E cells were co‐incubated with high glucose and melatonin (25 and 50 μM). Melatonin supplementation abrogated the diabetes‐induced renal injury and improved renal function in diabetic rats. Immunoblot analysis of renal tissue lysates revealed improved expression of AMPK, as well as upregulated the expression of nuclear factor erythroid 2‐related factor 2, SIRT1, PGC‐1α, TFAM and enhanced autophagy upon melatonin treatment in diabetic rats. Likewise, melatonin treatment in high glucose exposed NRK‐52E cells improved expression of AMPK, enhanced mitochondrial biogenesis and positively modulated autophagy. However, these effects were repressed upon inhibition of AMPK activity in NRK‐52E cells by treatment of Compound‐C, suggesting that the protective effects of melatonin were mainly mediated through activation of AMPK. These results suggest that melatonin might mediate the renoprotective effect by upregulating the AMPK/SIRT1 axis, enhancing the autophagy and mitochondrial health in DIabetic Nephropathy.

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Section: Introductionmentioning

confidence: 99%

Melatonin prevents diabetes‐induced nephropathy by modulating the AMPK/SIRT1 axis: Focus on autophagy and mitochondrial dysfunction

Jain

Sherkhane

Kalavala

et al. 2022

Cell Biology International

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“…Indeed, MRA such as eplerenone and spironolactone reduce the eGFR in the acute phase; however, they also exert a nephroprotective effect on the long-run [ 74 ]. This has also been demonstrated for finerenone [ 75 , 76 , 77 , 78 ].…”

Section: Other Examplesmentioning

confidence: 56%

A Shared Nephroprotective Mechanism for Renin-Angiotensin-System Inhibitors, Sodium-Glucose Co-Transporter 2 Inhibitors, and Vasopressin Receptor Antagonists: Immunology Meets Hemodynamics

Capolongo

Capasso

Viggiano

2022

IJMS

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A major paradigm in nephrology states that the loss of filtration function over a long time is driven by a persistent hyperfiltration state of surviving nephrons. This hyperfiltration may derive from circulating immunological factors. However, some clue about the hemodynamic effects of these factors derives from the effects of so-called nephroprotective drugs. Thirty years after the introduction of Renin-Angiotensin-system inhibitors (RASi) into clinical practice, two new families of nephroprotective drugs have been identified: the sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the vasopressin receptor antagonists (VRA). Even though the molecular targets of the three-drug classes are very different, they share the reduction in the glomerular filtration rate (GFR) at the beginning of the therapy, which is usually considered an adverse effect. Therefore, we hypothesize that acute GFR decline is a prerequisite to obtaining nephroprotection with all these drugs. In this study, we reanalyze evidence that RASi, SGLT2i, and VRA reduce the eGFR at the onset of therapy. Afterward, we evaluate whether the extent of eGFR reduction correlates with their long-term efficacy. The results suggest that the extent of initial eGFR decline predicts the nephroprotective efficacy in the long run. Therefore, we propose that RASi, SGLT2i, and VRA delay kidney disease progression by controlling maladaptive glomerular hyperfiltration resulting from circulating immunological factors. Further studies are needed to verify their combined effects.

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“…Concomitant use of SGLT2 inhibitor with finerenone decreased CKD progression risk, and with esaxerenone decreased hyperkalemia risk in patients with CKD and T2DM [ 79 , 109 ]. The effects of finerenone on kidney and cardiovascular outcomes were consistent irrespective of the use of glucagon-like peptide-1 receptor agonist (GLP-1RA) [ 110 ]. More details about combination therapy with nonsteroidal MRAs remain to be verified.…”

Section: Discussionmentioning

confidence: 99%

Nonsteroidal Mineralocorticoid Receptor Antagonist Eliciting Cardiorenal Protection Is a New Option for Patients with Chronic Kidney Disease

Liu¹,

Yu²

2022

Kidney Dis

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Background: Mineralocorticoid receptor antagonists (MRAs) protect cardiorenal function by robust anti-inflammatory and antifibrotic functions beyond classical functions of maintaining fluid and electrolyte homeostasis. The application of traditional steroidal MRAs to chronic kidney disease (CKD) has been limited by adverse events, especially when combined with renin-angiotensin system (RAS) inhibitors, guideline-recommend drugs for CKD patients. Recently, the development of non-steroidal MRAs gives patients with CKD a promising option. Summary: The discovery of non-steroidal MRAs is based on the molecular structure of the mineralocorticoid receptor (MR) and differ in structure from spironolactone, a progesterone derivative. The structure of non-steroidal MRAs determines their more effective and selective inhibition of MR providing patients more benefits with fewer adverse effects than MRAs. Recently, two types of non-steroidal MRAs, finerenone and esaxerenone, have been authorized for clinical use. We elaborate on the physiological and pathophysiological mechanisms of MR, review the history of MRAs, compare two generations of MRAs, and introduce the forward clinical trials of finerenone and esaxerenone. Key Messages: Finerenone reduces the cardiovascular and kidney composite outcomes in diabetic patients with CKD eliciting a cardiorenal protection effect. Esaxerenone can effectively reduce blood pressure in hypertensive patients and albuminuria in diabetic patients with CKD. The risk of hyperkalemia is controllable and acceptable through the serum potassium-based dose titrate. Combination therapy with sodium glucose cotransport-2 (SGLT2) inhibition or a new potassium binder may be a safer and more efficient approach.

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Efficacy and safety of finerenone in patients with chronic kidney disease and type 2 diabetes by GLP‐1RA treatment: A subgroup analysis from the FIDELIO‐DKD trial

Cited by 49 publications

References 36 publications

Melatonin prevents diabetes‐induced nephropathy by modulating the AMPK/SIRT1 axis: Focus on autophagy and mitochondrial dysfunction

Melatonin prevents diabetes‐induced nephropathy by modulating the AMPK/SIRT1 axis: Focus on autophagy and mitochondrial dysfunction

A Shared Nephroprotective Mechanism for Renin-Angiotensin-System Inhibitors, Sodium-Glucose Co-Transporter 2 Inhibitors, and Vasopressin Receptor Antagonists: Immunology Meets Hemodynamics

Nonsteroidal Mineralocorticoid Receptor Antagonist Eliciting Cardiorenal Protection Is a New Option for Patients with Chronic Kidney Disease

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