ReviewPflugers Archiv : European journal of physiology2015
Urinary serine proteases and activation of ENaC in kidney--implications for physiological renal salt handling and hypertensive disorders with albuminuria.
Review in Pflugers Archiv : European journal of physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 61 citations in OpenAlex.
- A Randomized Trial of Distal Diuretics versus Dietary Sodium Restriction for Hypertension in Chronic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2020Trial
- Comparative and diagnostic evaluation of maternal serum prostasin in early-onset preeclampsia.Medicine · 2026Article
- Resistance to doxorubicin-induced proteinuria and proteolytic activation of ENaC in 129S2/SvPas mice.Physiological reports · 2025Article
- ENaCγ in Urinary Extracellular Vesicles as an Indicator of MR Signaling in Primary Aldosteronism.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Article
- Urinary Plasminogen as a Marker of Disease Progression in Human Glomerular Disease.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2024Article
- Nephrotic Syndrome: From Pathophysiology to Novel Therapeutic Approaches.Biomedicines · 2024Review
- Aldosterone: Renal Action and Physiological Effects.Comprehensive Physiology · 2023Article
- Sodium retention in nephrotic syndrome is independent of the activation of the membrane-anchored serine protease prostasin (CAP1/PRSS8) and its enzymatic activity.Pflugers Archiv : European journal of physiology · 2022Article
- Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 Replication by Hypertonic Saline Solution in Lung and Kidney Epithelial Cells.ACS pharmacology & translational science · 2021Article
- Sex differences in prenatal programming of hypertension by dexamethasone.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- Plasminogen deficiency does not prevent sodium retention in a genetic mouse model of experimental nephrotic syndrome.Acta physiologica (Oxford, England) · 2021Article
- Plasminogenuria is associated with podocyte injury, edema, and kidney dysfunction in incident glomerular disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Pathophysiology of Diuretic Resistance and Its Implications for the Management of Chronic Heart Failure.Hypertension (Dallas, Tex. : 1979) · 2020Review
- Recent insights into sodium and potassium handling by the aldosterone-sensitive distal nephron: implications on pathophysiology and drug discovery.Journal of nephrology · 2020Review
- Deletion of the serine protease CAP2/Tmprss4 leads to dysregulated renal water handling upon dietary potassium depletion.Scientific reports · 2019Article
- Cathepsin B increases ENaC activity leading to hypertension early in nephrotic syndrome.Journal of cellular and molecular medicine · 2019Article
- Is urinary excretion of plasminogen associated with development of pre-eclampsia? An observational, explorative case-control study.BMJ open · 2019Observational
- A Novel Mechanism of Renal Microcirculation Regulation: Connecting Tubule-Glomerular Feedback.Current hypertension reports · 2019Review
- Urinary Plasmin(ogen) as a Prognostic Factor for Hypertension.Kidney international reports · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Serine proteases, both soluble and cell-attached, can activate the epithelial sodium channel (ENaC) proteolytically through release of a putative 43-mer inhibitory tract from the ectodomain of the γ-subunit. ENaC controls renal Na(+) excretion and loss-of-function mutations lead to low blood pressure, while gain-of-function mutations lead to impaired Na(+) excretion, hypertension, and hypokalemia. We review an emerging pathophysiological concept that aberrant glomerular filtration of plasma proteases, e.g., plasmin, prostasin, and kallikrein, contributes to proteolytic activation of ENaC, both in acute conditions with proteinuria, like nephrotic syndrome and preeclampsia, and in chronic diseases, such as diabetes with microalbuminuria. A vast literature on renin-angiotensin-aldosterone system and volume homeostasis from the last four decades show a number of common characteristics for conditions with albuminuria compatible with impaired renal Na(+) excretion: hypertension and volume retention is secondary to proteinuria in, e.g., preeclampsia and nephrotic syndrome; plasma concentrations of renin, angiotensin II, and aldosterone are frequently suppressed in proteinuric conditions, e.g., preeclampsia and diabetic nephropathy; blood pressure is salt-sensitive in conditions with microalbuminuria/proteinuria; and extracellular volume is expanded, plasma atrial natriuretic peptide (ANP) concentration is increased, and diuretics, like amiloride and spironolactone, are effective blood pressure-reducing add-ons. Active plasmin in urine has been demonstrated in diabetes, preeclampsia, and nephrosis. Urine from these patients activates, plasmin-dependently, amiloride-sensitive inward current in vitro. The concept predicts that patients with albuminuria may benefit particularly from reduced salt intake with RAS blockers; that distally acting diuretics, in particular amiloride, are warranted in low-renin/albuminuric conditions; and that urine serine proteases and their activators may be pharmacological targets.
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