Intrauterine growth retardation aggravates the course of acute mesangioproliferative glomerulonephritis in the rat.
Intrauterine growth retardation (IUGR) aggravates the course of acute mesangioproliferative glomerulonephritis (GN) in the rat. Observational studies in children suggest that IUGR may be associated with a severe course of kidney diseases such as IgA nephropathy. We tested the hypothesis that IUGR leads to aggravation of acute mesangioproliferative GN in former IUGR rats. IUGR was induced in Wistar rats by isocaloric protein restriction in pregnant dams. Litter size was reduced to six male neonates in low protein animals (LP) and normal protein animals (NP). At 8 weeks GN was induced by injection of an anti-Thy-1.1 antibody. Rats were killed on days 4 and 14 after induction of GN and kidneys were investigated for inflammation and sclerosis using real-time polymerase chain reaction and histological methods. On day 4 after induction of GN, LP animals showed more glomerulosclerosis and tubulointerstitial lesions. On day 14, inflammatory markers (expression of monocyte chemoattractant protein 1, osteopontin, tumor necrosis factor and interleukin-6), extracellular matrix accumulation and markers of sclerosis (plasminogen activator inhibitor-1 expression, transforming growth factor-beta1 expression, score for glomerulosclerosis, glomerular deposition of collagen I and collagen IV) were more severe in LP animals. Some degree of induction of inflammatory and profibrotic markers was also present in non-nephritic LP animals. However, these rats did not display marked glomerulosclerosis or interstitial fibrosis. We conclude that after IUGR inflammatory damage is aggravated and the reparation of the kidney is impaired during the course of acute mesangioproliferative GN, leading to more sclerotic lesions.
Plank
C
C
Department of Pediatrics and Adolescent Medicine, University Erlangen-Nuremberg, Erlangen, Germany. christian.plank@kinder.imed.uni-erlangen.de
Ostreicher
I
I
Hartner
A
A
Marek
I
I
Struwe
F G
FG
Amann
K
K
Hilgers
K F
KF
Rascher
W
W
Dötsch
J
J
D000818:Animals; D018753:Diet, Protein-Restricted / Q000009:adverse effects; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology / Q000503:physiopathology*; D005355:Fibrosis / Q000503:physiopathology; D005921:Glomerulonephritis / Q000150:complications / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology; D007518:Isoantibodies; D007668:Kidney / Q000503:physiopathology; D008297:Male; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D007518:Isoantibodies; C035678:anti-Thy antibody