ArticleJournal of the American Society of Nephrology : JASN2009
Plasmin in nephrotic urine activates the epithelial sodium channel.
Article in Journal of the American Society of Nephrology : JASN, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01918488 (Increased Activity of the Epithelial Sodium Channel), which is not on this map. Cited by 139 papers, 1 of them a synthesis that pooled it.
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.
Increased Activity of the Epithelial Sodium Channel (ENaC) in Diabetic Nephropathy
Who cites it
139 citing papers in PubMed, 1 synthesis or guideline pooled it, 258 citations in OpenAlex.
- Management of congenital nephrotic syndrome: consensus recommendations of the ERKNet-ESPN Working Group.Nature reviews. Nephrology · 2021Guideline
- Improved home BP profile with dapagliflozin is associated with amelioration of albuminuria in Japanese patients with diabetic nephropathy: the Yokohama add-on inhibitory efficacy of dapagliflozin on albuminuria in Japanese patients with type 2 diabetes study (Y-AIDA study).Cardiovascular diabetology · 2019Trial
- Albuminuria is associated with an increased prostasin in urine while aldosterone has no direct effect on urine and kidney tissue abundance of prostasin.Pflugers Archiv : European journal of physiology · 2017Trial
- Kidney organoids as a platform to study plasminogen-induced injury and uPA-based therapies.Stem cells translational medicine · 2026Article
- Urokinase Promotes Redundantly Intratubular C3a-Formation But Not ENaC-Driven Hypertension in DOCA/Salt Kidney Injury.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Article
- Resistance to doxorubicin-induced proteinuria and proteolytic activation of ENaC in 129S2/SvPas mice.Physiological reports · 2025Article
- Urinary plasminogen as an early marker of diabetic kidney disease in children with type 1 diabetes mellitus: a cross-sectional study.European journal of pediatrics · 2025Article
- Article
- Diuretics in patients with chronic kidney disease.Nature reviews. Nephrology · 2025Review
- Crosstalk between glomeruli and tubules.Nature reviews. Nephrology · 2025Review
- Transmembrane Serine Protease 2 and Proteolytic Activation of the Epithelial Sodium Channel in Mouse Kidney.Journal of the American Society of Nephrology : JASN · 2025Article
- Article
- Article
- Ascites: Under- and Overfill: Is Amiloride the Answer?Journal of the American Society of Nephrology : JASN · 2024Article
- Genetically conditioned interaction among microRNA-155, alpha-klotho, and intra-renal RAS in male rats: Link to CKD progression.Physiological reports · 2024Article
- Article
- Influence of proteolytic cleavage of ENaC's γ subunit upon NaAmerican journal of physiology. Renal physiology · 2024Article
- Epithelial NaComprehensive Physiology · 2024Review
- Nephrotic Syndrome: From Pathophysiology to Novel Therapeutic Approaches.Biomedicines · 2024Review
79 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteinuria and increased renal reabsorption of NaCl characterize the nephrotic syndrome. Here, we show that protein-rich urine from nephrotic rats and from patients with nephrotic syndrome activate the epithelial sodium channel (ENaC) in cultured M-1 mouse collecting duct cells and in Xenopus laevis oocytes heterologously expressing ENaC. The activation depended on urinary serine protease activity. We identified plasmin as a urinary serine protease by matrix-assisted laser desorption/ionization time of-flight mass spectrometry. Purified plasmin activated ENaC currents, and inhibitors of plasmin abolished urinary protease activity and the ability to activate ENaC. In nephrotic syndrome, tubular urokinase-type plasminogen activator likely converts filtered plasminogen to plasmin. Consistent with this, the combined application of urokinase-type plasminogen activator and plasminogen stimulated amiloride-sensitive transepithelial sodium transport in M-1 cells and increased amiloride-sensitive whole-cell currents in Xenopus laevis oocytes heterologously expressing ENaC. Activation of ENaC by plasmin involved cleavage and release of an inhibitory peptide from the ENaC gamma subunit ectodomain. These data suggest that a defective glomerular filtration barrier allows passage of proteolytic enzymes that have the ability to activate ENaC.
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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 OpenQuestion graph.