Glomerular charge barrier and development of proteinuria in passive Heymann nephritis.
OBJECTIVE
Passive Heymann nephritis (PHN) in rats is a commonly used model of membranous glomerulonephritis in man where the cause of proteinuria is not fully resolved. This study was designed to investigate the role of the glomerular charge barrier in development of PHN proteinuria.


METHODS
We studied female Sprague-Dawley rats (n = 33) at days 0, 2, 5 and 14 after induction of PHN by injection of antiserum against renal tubular epithelial antigens (anti-Fx1A). Measuring clearance of chymotrypsinogen A (Chym, MW 25,000, 21 A) and similar sized anionic chymotrypsinogen (aChym), together with (51)Cr-EDTA, we hypothesized an increased sieving coefficient (theta) of aChym in the early phase of PHN due to impairment of the glomerular charge barrier.


RESULTS
No proteinuria was seen at day 2 (5.8 +/- 1.4 mg/ 24 h, p > 0.05), while protein excretion increased to 23.2 +/- 2.9 mg/24 h (p < 0.05) at day 5 (84 +/- 2% albumin) and further to 544.3 +/- 51.1 mg/24 h (p < 0.01) at day 14 (60 +/- 1% albumin; p < 0.01, day 5 vs. day 14). theta aChym was similar to control at day 2 (0.49 +/- 0.03, p > 0.05), increased at day 5 to 0.62 +/- 0.02 (p < 0.01) but decreased at day 14 to 0.39 +/- 0.02 (p < 0.01). The sieving coefficient of Chym (theta Chym) was decreased at day 14 (p < 0.05). The ratio of theta aChym to theta Chym was increased at day 5 (p < 0.01) but was elsewhere similar to control.


CONCLUSIONS
The increased ratio of theta aChym to theta Chym and selective albuminuria at day 5 indicates an initial impairment of the glomerular charge barrier in PHN.
Christiansen
Rolf E F
RE
Renal Research Group, Institute of Medicine, Haukeland University Hospital, Bergen, Norway. rolf.christiansen@meda.uib.no
Kolmannskog
Odd
O
Leh
Sabine
S
Iversen
Bjarne M
BM
Tenstad
Olav
O
D000818:Animals; D002919:Chymotrypsinogen / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D005919:Glomerular Filtration Rate; D015433:Glomerulonephritis, Membranous / Q000150:complications*; D007678:Kidney Glomerulus / Q000503:physiopathology*; D011507:Proteinuria / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002919:Chymotrypsinogen