Mechanisms of sodium retention in nephrotic syndrome
| Autor: | Boye L. Jensen, Per Svenningsen, Gitte R. Hinrichs |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Epithelial sodium channel
Proteases Nephrotic Syndrome 030232 urology & nephrology Hypertension/etiology 030204 cardiovascular system & hematology Pharmacology 03 medical and health sciences 0302 clinical medicine Edema Internal Medicine Medicine Animals Humans Aprotinin Epithelial Sodium Channels Triamterene business.industry Sodium Extracellular vesicle medicine.disease Epithelial Sodium Channels/physiology Serine proteases Amiloride Proteinuria Nephrotic Syndrome/metabolism Sodium/metabolism Nephrology Hypertension medicine.symptom business Nephrotic syndrome medicine.drug |
| Zdroj: | Hinrichs, G R, Jensen, B L & Svenningsen, P 2020, ' Mechanisms of sodium retention in nephrotic syndrome ', Current Opinion in Nephrology & Hypertension, vol. 29, no. 2, pp. 207-212 . https://doi.org/10.1097/MNH.0000000000000578 |
| ISSN: | 1473-6543 |
| DOI: | 10.1097/MNH.0000000000000578 |
| Popis: | PURPOSE OF REVIEW: Proteinuria in nephrotic syndrome is associated with sodium retention and edema. Recent studies from mice, rats and humans have shown that the sodium retention depends on urinary serine proteases and that it can be mitigated by blockers (amiloride, triamterene) of the epithelial sodium channel ENaC. The present review outlines the mechanisms of protease-stimulated sodium retention during proteinuric diseases.RECENT FINDINGS: Inhibition of protease activity in nephrotic mice using aprotinin alleviates sodium retention. From both human and mice studies, an increased proteolytic cleavage of the γENaC subunit plays a role in ENaC activation. In animal models, urokinase-plasmin contributes but not as sole mediators of sodium retention. Across experimental models, human case reports and small intervention trials, amiloride alleviates nephrotic sodium retention and low-renin hypertension with high efficacy.SUMMARY: Although the exact mechanisms for proteolytic ENaC activation are not resolved, multiple, redundant proteases are involved. Experimental and clinical evidence indicate that aberrant proteolytic ENaC activation is a primary driver of sodium retention in nephrotic syndrome and contributes to hypertension in conditions with low-grade proteinuria. Thus, we foresee increased and personalized use of amiloride treatment of nephrotic and other proteinuric disease patients with associated sodium retention and hypertension. |
| Databáze: | OpenAIRE |
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