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PMID: 7952502 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Podocyte damage is a critical step in the development of glomerulosclerosis in the uninephrectomised-desoxycorticosterone hypertensive rat.

Virchows Archiv : an international journal of pathology ·Vol. 425 ·No. 2 ·1994-00-00 ·Pages 181-93

Kretzler M, Koeppen-Hagemann I, Kriz W

Abstract

The progressive renal disease model of chronic uninephrectomy-desoxycorticosterone-trimethylacetate (UNX-DOCA) hypertension is associated with mesangial proliferation as a major disease mechanism. A detailed structural analysis of the alterations in glomerular structure which accompany the development of sclerosis in this model has not been made. Male Munich-Wistar rats underwent UNX, received weekly injections of the aldosterone agonist DOCA and 1% sodium chloride as drinking solution and were compared with sham operated controls (CON). Thirty eight days after onset, UNX animals had an albuminuria of 183 +/- 180 mg/day versus 0.38 +/- 0.22 mg/day in CON. Kidneys were fixed by total body perfusion and renal tissue processed for light and electron-microscopy. Superficial and deep total glomerular volume increased from 2.18 +/- 0.15 (deep: 2.57 +/- 0.24) 10(6) microns 3 in CON to 3.98 +/- 0.81 (deep: 3.95 +/- 0.63) 10(6) microns 3 in UNX. In addition to overall tuft hypertrophy, structural analysis revealed severe destruction of tuft architecture with mesangial expansion and/or capillary ballooning, leading to local tuft enlargements. Podocytes overlying the expanded areas appeared unable to adapt to cover the increased tuft surfaces. They developed severe lesions in cell architecture leading to denudation of glomerular basement membrane (GBM)-areas. "Naked" GBM appears to represent a nidus for hyalinosis, thrombosis and synechia formation, which progresses to segmental sclerosis. In the UNX-DOCA model of chronic glomerular hypertension local mesangial expansion was frequently encountered but no evidence was found that mesangial proliferation and matrix production proceeded to sclerosis. The crucial damage to the glomerulus in this model would appear to be attributable to podocyte failure, with the resultant GBM denudation triggering synechia formation, hyalinosis and ultimately glomerulosclerosis.

MeSH Terms
Animals Desoxycorticosterone Glomerular Mesangium/pathology Glomerulosclerosis, Focal Segmental/etiology,pathology Hypertension, Renal/chemically induced,complications,pathology Kidney Glomerulus/pathology,ultrastructure Male Necrosis Nephrectomy Rats Rats, Wistar
Chemicals
Desoxycorticosterone
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kretzler M
Anatomy and Cell Biology Institute I, University of Heidelberg, Germany.
Koeppen-Hagemann I
Kriz W
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Article Info
Journal
Virchows Archiv : an international journal of pathology
Abbr.
Virchows Arch
ISSN
0945-6317
DOI
10.1007/BF00230355
Published
1994-00-00
Pages
181-93
Language
English
Region
Germany
NLM ID
9423843
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00230355 View journal details
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