Mechanisms of tubular volume retention in immune-mediated glomerulonephritis.
Glomerulonephritis is characterized by hematuria, proteinuria, hypertension, and edema, but the mechanisms contributing to volume disorders are controversial. Here we used the rat anti-Thy1 model of mesangioproliferative glomerulonephritis to test the hypothesis that disturbed salt and water homeostasis is based on tubular epithelial changes that cause salt retention. In this model there was an early onset of pronounced proteinuria and lipiduria associated with reduced fractional sodium excretion and a lowering of the renin-angiotensin-aldosterone system. The glomerular filtration rate and creatinine clearance were decreased on day 6. There was a reduced abundance of the major salt and water transport proteins on the proximal tubular brush border membrane and which paralleled cellular protein overload, enhanced membrane cholesterol uptake and cytoskeletal changes. Alterations in thick ascending limb were moderate. Changes in the collecting ducts were characterized by an enhanced abundance and increased subunit cleavage of the epithelial sodium channel, both events consistent with increased sodium reabsorption. We suggest that irrespective of the proximal tubular changes, altered collecting duct sodium reabsorption may be crucial for volume retention in acute glomerulonephritis. We suggest that enhanced proteolytic cleavage of ion transporter subunits might be a novel mechanism of channel activation in glomerular diseases. Whether these proteases are filtered or locally secreted awaits determination.
Gadau
Juliane
J
Institute of Anatomy, Charité Universitätsmedizin, Berlin, Germany.
Peters
Harm
H
Kastner
Christian
C
Kühn
Hartmut
H
Nieminen-Kelhä
Melina
M
Khadzhynov
Dmytro
D
Krämer
Stephanie
S
Castrop
Hayo
H
Bachmann
Sebastian
S
Theilig
Franziska
F
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D053503:Epithelial Sodium Channels / Q000032:analysis / Q000378:metabolism; D005921:Glomerulonephritis / Q000276:immunology / Q000503:physiopathology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D012964:Sodium / Q000378:metabolism; D014882:Water-Electrolyte Balance
D002352:Carrier Proteins; D053503:Epithelial Sodium Channels; D012964:Sodium