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Experimental acute ischemic renal failure and anticoagulation
Linköping University, Department of Molecular and Clinical Medicine, Forensic Medicine. Linköping University, Faculty of Health Sciences.
1998 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis is based on experimental studies on acute renal failure (ARF) in rats. The model employed is that of renal artery clamping, which causes a standardized, ischemic trauma to the kidney. The proximate objective of the investigations was to study iflocal coagulation in the kidney may be induced by a pure ischemic trauma, and whether such a coagulation could be of importance for the development of ARF in this experimental model.

The content of isotope-labeled fibrinogen and albumin was determined in postischemic kidneys and controls. After 60rnin of unilateral ischemia, the fibrin(ogen)/degradation products (FIB) and albumin content of the kidney increased rapidly and significantly, approximately averaging 200% of controls. The total kidney weight increased only to 130% of controls. Pretreatment with heparin in a dose of 2000 IU/kg BW, markedly attenuated the increase in kidney weight and content of FIB and albumin.

Pretreatment with a lower dose of heparin, 400 IU!kg BW, and warfarin (given intraperitoneally 24 h before the experiment) produced a similar reduction of these parameters, whereas pretreatment with a heparin analog, devoid of anticoagulant effect, did not.

In post-ischemic kidneys, scanning electron microscopy (SEM) of cautiously handled freezedried tissue revealed granular and fibrillary material in the tubules and in Bowman's space, at some locations displaying prominent network patterns. Immunofluorescence against FIB showed immunoreactive material in vasa recta, the peritubular capillaries, Bowman's space and in the tubules. By transmission electron microscopy (TEM), fibrin strands lacking periodicity were seen. As compared to controls, the postischemic kidneys generally showed a marked dilatation of Bowman's capsule. No fibrin deposition was seen in heparin pretreated animals.

To determine if anticoagulation exerts the described effects by prevention of tubular obstructions or by attenuation of increased glomerular permeability, morphometry of glomeruli was performed by light microscopy and TEM Postischemic kidneys from rats pretreated with saline showed a marked widening of Bowman's space, most likely due to tubular obstruction, whereas Bowman's space width in anticoagulated rats did not differ from controls. Structural changes of the podocyte foot processes as a marker of increased macromolecular permeability were severe in both saline pretreated and anticoagulated kidneys.

Glomerular filtration rate fell to 6% of controls after 40 min of ischemia. Warfarin-pretreatment attenuated this decrease significantly. Urinary protein excretion increased in both salinepretreated and anticoagulated rats. The excretion of FIB was significantly increased in warfarinpretreated rats, consistent with the previous observation of an attenuation of FIB content of postischemic kidneys by anticoagulation. This result thus suggests that warfarin did not prevent macromolecular sieving, but reduced the formation of protein-containing tubular casts.

In summary, these studies show that a pure ischemic injury to the kidney results in a local coagulation in the kidney, most prominently within Bowman's space and in the tubules. It is suggested that the increased glomerular permeability to macromolecules causes sieving of fibrinogen, which may precipitate in Bowman's space and tubuli and promote the development of tubular obstructions.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 1998. , 56 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 554
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-28558Local ID: 13711ISBN: 91-7219-070-1OAI: diva2:249369
Public defence
1998-05-08, Berzeliussalen, Universitetssjukhuset, Linköping, 13:00 (Swedish)
Papers, included in the Ph.D. thesis, are not registered and included in the posts from 1999 and backwards.Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-07-27Bibliographically approved

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