Mechanisms of renal NaCl retention in proteinuric disease

In diseases with proteinuria, for example nephrotic syndrome and pre‐eclampsia, there often are suppression of plasma renin–angiotensin–aldosterone system components, expansion of extracellular volume and avid renal sodium retention. Mechanisms of sodium retention in proteinuria are reviewed. In ani...

Full description

Saved in:

Bibliographic Details
Published in:	Acta Physiologica Vol. 207; no. 3; pp. 536 - 545
Main Authors:	Svenningsen, P., Friis, U. G., Versland, J. B., Buhl, K. B., Møller Frederiksen, B., Andersen, H., Zachar, R. M., Bistrup, C., Skøtt, O., Jørgensen, J. S., Andersen, R. F., Jensen, B. L.
Format:	Journal Article
Language:	English
Published:	England Blackwell Publishing Ltd 01-03-2013 Wiley Subscription Services, Inc
Subjects:	Animals Blood Pressure Disease Models, Animal Diuretics - therapeutic use ENaC Epithelial Sodium Channels - drug effects Epithelial Sodium Channels - metabolism Fibrinolysin - metabolism Glomerular Filtration Rate Humans hypertension Ion Channel Gating Kidney - drug effects Kidney - metabolism Kidney - physiopathology Kidney Diseases - drug therapy Kidney Diseases - metabolism Kidney Diseases - physiopathology Kidney Diseases - urine Kidneys nephrosis oedema plasmin pre-eclampsia Preeclampsia Proteins proteinuria Proteinuria - drug therapy Proteinuria - metabolism Proteinuria - physiopathology Proteinuria - urine Renin-Angiotensin System Retention Rodents Sodium Sodium Chloride, Dietary - metabolism Sodium Chloride, Dietary - urine Water-Electrolyte Balance
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	In diseases with proteinuria, for example nephrotic syndrome and pre‐eclampsia, there often are suppression of plasma renin–angiotensin–aldosterone system components, expansion of extracellular volume and avid renal sodium retention. Mechanisms of sodium retention in proteinuria are reviewed. In animal models of nephrotic syndrome, the amiloride‐sensitive epithelial sodium channel ENaC is activated while more proximal renal Na+ transporters are down‐regulated. With suppressed plasma aldosterone concentration and little change in ENaC abundance in nephrotic syndrome, the alternative modality of proteolytic activation of ENaC has been explored. Proteolysis leads to putative release of an inhibitory peptide from the extracellular domain of the γ ENaC subunit. This leads to full activation of the channel. Plasminogen has been demonstrated in urine from patients with nephrotic syndrome and pre‐eclampsia. Urine plasminogen correlates with urine albumin and is activated to plasmin within the urinary space by urokinase‐type plasminogen activator. This agrees with aberrant filtration across an injured glomerular barrier independent of the primary disease. Pure plasmin and urine samples containing plasmin activate inward current in single murine collecting duct cells. In this study, it is shown that human lymphocytes may be used to uncover the effect of urine plasmin on amiloride‐ and aprotinin‐sensitive inward currents. Data from hypertensive rat models show that protease inhibitors may attenuate blood pressure. Aberrant filtration of plasminogen and conversion within the urinary space to plasmin may activate γ ENaC proteolytically and contribute to inappropriate NaCl retention and oedema in acute proteinuric conditions and to hypertension in diseases with chronic microalbuminuria/proteinuria.
Bibliography:	ArticleID:APHA12047 istex:BB60AB2AABE676EC329B3EF485312E49765FBFB1 ark:/67375/WNG-D79BRHD3-B ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1
ISSN:	1748-1708 1748-1716
DOI:	10.1111/apha.12047