Trial reportJCI insight2023
Mineralocorticoid receptor antagonism in diabetes reduces albuminuria by preserving the glomerular endothelial glycocalyx.
Trial report in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 58 citations in OpenAlex.
- Interplay of serum potassium and kidney function with finerenone in heart failure with mildly reduced or preserved ejection fraction: Findings from FINEARTS-HF.European journal of heart failure · 2025Trial
- Heparanase inhibition prevents glycocalyx damage and albuminuria in experimental minimal change disease.Clinical and translational medicine · 2026Article
- Endothelial-erythrocyte glycocalyx exchange enables liquid biopsies of endothelial function.Nature communications · 2026Article
- The glomerular endothelial glycocalyx as a therapeutic target in proteinuric kidney disease.Nature reviews. Nephrology · 2026Review
- Albuminuria Is the Key Driver of Kidney Benefit with Aldosterone Receptor Antagonists in Type 2 Diabetes.Journal of the American Society of Nephrology : JASN · 2026Article
- Podocyte-directed VEGFC gene therapy prevents increased glomerular permeability and glycocalyx damage in experimental type 1 diabetes.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Metabolic syndrome and kidney dysfunction: emerging molecular and cellular mechanisms at the metabolic-renal interface.Frontiers in endocrinology · 2026Review
- Triple therapy of RAS inhibitors, dapagliflozin, and finerenone in diabetic kidney disease patients with nephrotic-range proteinuria: a real-world study.Scientific reports · 2025Article
- The nonsteroidal MR antagonist finerenone reverses Western diet-induced kidney disease by regulating mitochondrial and lipid metabolism and inflammation.American journal of physiology. Renal physiology · 2025Article
- Heparanase 2 Modulates Vascular Permeability via Heparan Sulfate-Dependent Growth Factor Signaling.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Glycocalyx Disintegration Is Associated with Mortality in Chronic Heart Failure.Journal of clinical medicine · 2025Article
- The status of studies on the mechanism of microcirculatory dysfunction in the process of diabetic kidney injury.Diabetology & metabolic syndrome · 2025Review
- Mineralocorticoid receptor blockage in kidney transplantation: too much of a good thing or not?International urology and nephrology · 2025Review
- Targeting Adenosine A2b Receptor Promotes Penile Rehabilitation of Refractory Erectile Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Endothelial CXCR2 deficiency attenuates renal inflammation and glycocalyx shedding through NF-κB signaling in diabetic kidney disease.Cell communication and signaling : CCS · 2024Article
- Heparanase inhibition as a systemic approach to protect the endothelial glycocalyx and prevent microvascular complications in diabetes.Cardiovascular diabetology · 2024Article
- Targeted identification of risk and treatment of diabetic kidney disease.Nature reviews. Nephrology · 2024Article
- Factors influencing glycocalyx degradation: a narrative review.Frontiers in immunology · 2024Review
- Aldosterone: Essential for Life but Damaging to the Vascular Endothelium.Biomolecules · 2023Review
- Diabetic Nephropathy and Gaseous Modulators.Antioxidants (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 4 countries.
Funding
Abstract
The glomerular endothelial glycocalyx (GEnGlx) forms the first part of the glomerular filtration barrier. Previously, we showed that mineralocorticoid receptor (MR) activation caused GEnGlx damage and albuminuria. In this study, we investigated whether MR antagonism could limit albuminuria in diabetes and studied the site of action. Streptozotocin-induced diabetic Wistar rats developed albuminuria, increased glomerular albumin permeability (Ps'alb), and increased glomerular matrix metalloproteinase (MMP) activity with corresponding GEnGlx loss. MR antagonism prevented albuminuria progression, restored Ps'alb, preserved GEnGlx, and reduced MMP activity. Enzymatic degradation of the GEnGlx negated the benefits of MR antagonism, confirming their dependence on GEnGlx integrity. Exposing human glomerular endothelial cells (GEnC) to diabetic conditions in vitro increased MMPs and caused glycocalyx damage. Amelioration of these effects confirmed a direct effect of MR antagonism on GEnC. To confirm relevance to human disease, we used a potentially novel confocal imaging method to show loss of GEnGlx in renal biopsy specimens from patients with diabetic nephropathy (DN). In addition, patients with DN randomized to receive an MR antagonist had reduced urinary MMP2 activity and albuminuria compared with placebo and baseline levels. Taken together, our work suggests that MR antagonists reduce MMP activity and thereby preserve GEnGlx, resulting in reduced glomerular permeability and albuminuria in diabetes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.