Structural analysis of the formation of glomerular microaneurysms in the Habu venom model

Uiker, S.; Kriz, Wilhelm

doi:10.1007/bf00191366

Cited by 20 publications

(18 citation statements)

References 27 publications

(56 reference statements)

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“…In accordance with the failure of the capillary support function of the mesangial cells, the capillary network is destroyed, and mesangiolytic lesions progress to segmental microaneurysmal ballooning [15]. In the present study, mesangiolytic lesions also developed into segmental microaneurysmal ballooning on day 3 (fig.…”

Section: Resultsmentioning

confidence: 55%

Recovery of Damaged Glomerular Capillary Network with Endothelial Cell Apoptosis in Experimental Proliferative Glomerulonephritis

Shimizu

Masuda

Kitamura

et al. 1998

Nephron

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Capillary repair can occur in damaged glomeruli in recovery models of glomerulonephritis (GN). In order to clarify whether capillary repair is an essential component in glomerular recovery from GN, we have examined the development of the capillary repair after inflammatory injury in both the repairing glomeruli and the segmental sclerotic scar lesions in Thy-1 GN. Mesangiolytic glomerular damage was induced in rats with anti-Thy-1.1 antibody administration. Diffuse mesangiolysis and segmental microaneurysmal ballooning developed in damaged glomeruli by day 3, with reduction of endothelial cellularity. Thereafter, histological proliferative GN developed between day 5 and week 3. Endothelial cell proliferation began on day 1 and peaked on day 5, and the number of glomerular endothelial cells increased and exceeded the level of control values on day 7. Angiogenic glomerular capillary repair occurred through the process of not only capillary regeneration from remaining endothelial cells in capillary aneurysmal lesions but also new capillary growth derived from the glomerular vascular poles by day 7. The number of glomerular capillary lumina also increased to the level of controls by week 3. Susbsequently, mesangial proliferative GN resolved, and most of the glomeruli recovered to their normal structure with the reconstruction of the capillary network by weeks 4–6. In the glomerular capillary repair, significant apoptosis of glomerular endothelial cells was present during the period of mild endothelial cell hypercellularity between day 7 and day 10 (0.06 ± 0.02 apoptotic endothelial cells/glomerular cross section vs. 0.00 ± 0.00 in controls, mean ± SEM; p < 0.05. In Thy-1 GN, most of the damaged glomeruli recovered with angiogenic capillary repair. However, segmental sclerotic scar lesions remained in 10–30% of the glomeruli with an incomplete repair of glomerular capillaries. Therefore, it is concluded that following the destruction of the glomerular capillary network in GN, angiogenic capillary repair plays an essential role in the recovery of damaged glomeruli, and incomplete capillary repair leads to sclerotic scar lesions in damaged glomeruli. Glomerular capillary repair occurs through the process of capillary regeneration from remaining endothelial cells as well as new glomerular capillary growth from the glomerular vascular poles. In glomerular capillary repair, apoptosis is necessary in regulating the number of intrinsic endothelial cells.

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Section: Resultsmentioning

confidence: 55%

Recovery of Damaged Glomerular Capillary Network with Endothelial Cell Apoptosis in Experimental Proliferative Glomerulonephritis

Shimizu

Masuda

Kitamura

et al. 1998

Nephron

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“…35 Agkistrodon halys snake venom also induces mesangiolysis, 36 and this damage has been reported after bites from the habu snake Trimeresurus flavoviridis. 37,38 The high proteolytic activity of the latter venom was thought to cause most of the damage to the glomerular mesangium 39,40 and could also account for B. moojeni venom-induced mesangiolysis.…”

Section: Discussionmentioning

confidence: 99%

“…40 In addition to the mesangium, the podocytes 41,42 and GBM 43 also provide a structural basis for capillary tuft support, and all undoubtedly participate in protecting the capillaries from ballooning or microaneurysm formation otherwise seen after mesangiolysis. 44 In summary, the current study demonstrates for the first time that glomerular changes are responsible for proteinuria and that both contribute to the nephrotoxicity in ARF caused by the intravenous administration of B. moojeni venom.…”

Section: Discussionmentioning

confidence: 99%

Bothrops moojeni snake venom-induced renal glomeruli changes in rat.

Bôer

Gontijo²,

Cruz‐Höfling³

2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. The venom of Bothrops moojeni has potent proteolytic and phospholipase A 2 activities. In previous work, we showed that intravenous injection of this venom in rats decreased creatinine clearance and caused tubular dysfunction and histopathological changes with no alterations in blood pressure. The current study used scanning and transmission electron microscopy to assess the ultrastructural changes caused by B. moojeni venom (0.4 mg/kg i.v.) in rat renal glomeruli and correlated these alterations with the severity of proteinuria 5 hours, 16 hours, and 48 hours after venom injection. The changes included mesangiolysis, glomerular microaneurysms, and glomerular basement membrane (GBM) abnormalities. In addition, there was a reduction in the number and width of podocyte pedicels, which caused a reduction in the number of filtration slits. Electron-dense amorphous material, which may be proteinaceous in origin, was found in the pedicels. The severity of the ultrastructural abnormalities correlated with the level of proteinuria. These morphophysiological changes were attributed to biochemical and physiological disturbances in the components of the GBM and mesangial matrix as well as in cytoskeleton-associated proteins of podocytic processes, and could account for the breakdown of optimal glomerular filtration barrier functioning. These results, together with the absence of appreciable glomerular fibrin deposits, support the hypothesis of a direct activity of B. moojeni venom on rat kidneys. Proteolytic activity of the venom on renal glomeruli could then contribute to the onset of acute renal failure, and would explain the clinical manifestations of renal injury after bites by this and other Bothrops species.

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“…Glomerular aneurysms are characteristic of the Habu-venom-induced glomerular disease, where they develop quickly (within a few hours) (23). At variance with a mesangial balloon, the capillaries rupture, leading, in conjunction with the loss of the GBM folding pattern, to blood-filled lobular aneurysms.…”

Section: Damage Developmentmentioning

confidence: 99%

“…At variance with a mesangial balloon, the capillaries rupture, leading, in conjunction with the loss of the GBM folding pattern, to blood-filled lobular aneurysms. It appears that as a consequence of the abnormal blood fluxes, ruptured capillaries are simply pushed aside and compressed to the GBM, resulting in the formation of quite irregular, frequently multilayered walls of the aneurysm (23). Aneurysms were only encountered in early stages of the disease; because they were comparably rare, it was impossible to study their further development.…”

Section: Damage Developmentmentioning

confidence: 99%

Pathways to Recovery and Loss of Nephrons in Anti-Thy-1 Nephritis

Kriz¹,

Hähnel²,

Hosser³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. The present histopathologic study of anti-Thy-1.1 models of mesangioproliferative glomerulonephritis in rats provides a structural analysis of damage development and of pathways to recovery and to nephron loss. As long as the disease remains confined to the endocapillary compartment, the damage may be resolved or recover with a mesangial scar. Irreversible lesions with loss of nephrons emerge from extracapillary processes with crucial involvement of podocytes, leading to tuft adhesions to Bowman's capsule (BC) and subsequent crescent formation. Two mechanisms appeared to be responsible: (1) Epithelial cell proliferation at BC and the urinary orifice and (2) misdirected filtration and filtrate spreading on the outer aspect of the nephron. Both may lead to obstruction of the tubule, disconnection from the glomerulus, and subsequent degeneration of the entire nephron. No evidence emerged to suggest that the kind of focal interstitial proliferation associated with the degeneration of injured nephrons was harmful to a neighboring healthy nephron.Glomerular diseases starting with mesangiolysis have a high probability of recovery. However, not all nephrons recover; some always undergo destruction; we therefore raised the following questions: (1) what is the crucial stage of damage that determines the subsequent recovery or progression and (2) what are the sequences of events leading either to the restitution or to the degeneration of the respective nephron? Thus, our primary question was not why a nephron degenerated or recovered but how these outcomes were achieved. A glomerulus, and all the more a nephron, are both complex structures; we therefore wanted to analyze to which extent the loss and, on the other hand, the reestablishment of the higher order structure were decisive for damage progression and recovery, respectively.The most common models used to study mesangiolysis and damage development starting therefrom are those that induce mesangial cell lysis with antibodies against the Thy 1.1 antigen of mesangial cells; the resulting disease is generally referred to as anti-Thy-1 nephritis. The classical experiments were performed either with polyclonal antibodies (1,2) or with the monoclonal antibody OX-7 (3). More recently, the monoclonal antibody 1-22-3 (4) has been shown to produce more severe damage. Administration of these antibodies in rats leads to a brisk complement-dependent lysis of the mesangial cells followed by the development of a mesangioproliferative glomerulonephritis.We used both the OX-7 and the 1-22-3 antibodies in two originally separate studies. Because disease development was more or less identical in both models, we combined both studies. This permitted us to analyze complete pathways of damage development and to provide step-by-step sequences of events leading from mesangiolysis via various intermediate stages to either the recovery or loss of a nephron. We think that these results are of considerable general interest when asking how nephrons degenerate in chronic renal disease. M...

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Structural analysis of the formation of glomerular microaneurysms in the Habu venom model

Cited by 20 publications

References 27 publications

Recovery of Damaged Glomerular Capillary Network with Endothelial Cell Apoptosis in Experimental Proliferative Glomerulonephritis

Recovery of Damaged Glomerular Capillary Network with Endothelial Cell Apoptosis in Experimental Proliferative Glomerulonephritis

Bothrops moojeni snake venom-induced renal glomeruli changes in rat.

Pathways to Recovery and Loss of Nephrons in Anti-Thy-1 Nephritis

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