Endothelial characteristics of glomerular capillaries in normal, mercuric chloride-induced, and gentamicin-induced acute renal failure in the rat.

Bulger, Ruth Ellen; Eknoyan, Garabed; Purcell, Daniel J.; Dobyan, Dennis C.

doi:10.1172/jci110950

Cited by 45 publications

(10 citation statements)

References 13 publications

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“…It has been reported that gentamicin administration could result in a decrease in the diameter and density of endothelial fenestrae, suggesting that the filtration rate per surface area was markedly reduced (26). However, these ultrastructural changes in permeability have not been always observed (27), despite the occurrence of a decrease in glomerular capillary ultrafiltration coeficient (28). The nephron mass reduction and the potential alterations in glomerular endothelial capillaries might have led to this glomerular hypertrophy, explaining the normal renal function measured.…”

Section: Discussionmentioning

confidence: 93%

Long-Term Effects of Mild Oligonephronia Induced In Utero by Gentamicin in the Rat

1991

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ABSTRACT. Renal clearance studies and morphologic observations were performed in rats aged 14, 21, and 28 d and 3, 6, 9, and 12 mo born with a 20% reduction in nephron number after administration of 75 mg/kg/d of gentamicin to their mothers during the second half of gestation. Gentamicin was still present in urine 3 mo after birth. Morphologic damage characteristic of gentamicin accumulation was observed in the kidney on d 14 and 21. Adequate compensatory adaptation to oligonephronia occurred for glomerular function within 14 d of birth, but tubular phosphate reabsorption was significantly low on d 21. On d 28, no evidence of histologic or functional damage to the kidney was observed. At 3 mo, mesangial lesions were observed in rats of the gentamicin group, whereas they were rarely present in 6-mo-old control rats. Furthermore, glomerular sclerotic lesions were already evident in about 5% of the juxtamedullary nephrons. The same percentage of injured nephrons was not observed before 12 mo in controls. Complementary morphologic data obtained in 24-mo-old rats showed that glomerulosclerosis involved 40% of the juxtamedullary nephron population at this age in animals of the gentamicin group versus 21% in controls.

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Section: Discussionmentioning

confidence: 93%

Long-Term Effects of Mild Oligonephronia Induced In Utero by Gentamicin in the Rat

1991

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“…Capillaries with continuous endothelium are the most common type and are typically found in skeletal muscle, cardiac muscle, and skin (288). However, the glomerular capillaries have endothelial cells with a large fenestrated area constituting 20 -50% of the entire endothelial surface (40). The unusually high density of fenestrae is thought to allow high permeability to water and small solutes in the glomerulus (73).…”

Section: Endotheliummentioning

confidence: 99%

Properties of the Glomerular Barrier and Mechanisms of Proteinuria

Haraldsson

Nyström²,

Deen³

2008

Physiological Reviews

715

634

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This review focuses on the intricate properties of the glomerular barrier. Other reviews have focused on podocyte biology, mesangial cells, and the glomerular basement membrane (GBM). However, since all components of the glomerular membrane are important for its function, proteinuria will occur regardless of which layer is affected by disease. We review the properties of endothelial cells and their surface layer, the GBM, and podocytes, discuss various methods of studying glomerular permeability, and analyze data concerning the restriction of solutes by size, charge, and shape. We also review the physical principles of transport across biological or artificial membranes and various theoretical models used to predict the fluxes of solutes and water. The glomerular barrier is highly size and charge selective, in qualitative agreement with the classical studies performed 30 years ago. The small amounts of albumin filtered will be reabsorbed by the megalin-cubulin complex and degraded by the proximal tubular cells. At present, there is no unequivocal evidence for reuptake of intact albumin from urine. The cellular components are the key players in restricting solute transport, while the GBM is responsible for most of the resistance to water flow across the glomerular barrier.

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“…Fenestrations associated with glomerular endothelial cells are a characteristic feature of the kidney (32,33). Such fenestrations are considered to allow for the filtration property of the glomerulus (34 -37).…”

Section: Anti-vegf Antibody and Proteinuria 12606mentioning

confidence: 99%

Neutralization of Circulating Vascular Endothelial Growth Factor (VEGF) by Anti-VEGF Antibodies and Soluble VEGF Receptor 1 (sFlt-1) Induces Proteinuria

Sugimoto

Hamano

Charytan

et al. 2003

Journal of Biological Chemistry

482

336

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There are about 2.5 million glomeruli in the kidneys each consisting of a barrel of glomerular basement membrane surrounded by glomerular endothelial cells on the inside and glomerular epithelial cells with established foot processes (podocytes) on the outside. Defects in this filtration apparatus lead to glomerular vascular leak or proteinuria. The role of vascular endothelial growth factor (VEGF) in the regulation of glomerular vascular permeability is still unclear. Recent studies indicate that patients receiving anti-VEGF antibody therapy may have an increased incidence of proteinuria. In a different setting, pregnancies complicated by preeclampsia are associated with elevated soluble VEGF receptor 1 protein (sFlt-1), endothelial cell dysfunction and proteinuria. These studies suggest that neutralization of physiologic levels of VEGF, a key endothelial survival factor, may lead to proteinuria. In the present study, we evaluated the potential of anti-VEGF neutralizing antibodies and sFlt-1 in the induction of proteinuria. Our studies demonstrate that anti-VEGF antibodies and sFlt-1 cause rapid glomerular endothelial cell detachment and hypertrophy, in association with down-regulation of nephrin, a key epithelial protein in the glomerular filtration apparatus. These studies suggest that down-regulation or neutralization of circulating VEGF may play an important role in the induction of proteinuria in various kidney diseases, some forms of cancer therapy and also in women with preeclampsia.

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Endothelial characteristics of glomerular capillaries in normal, mercuric chloride-induced, and gentamicin-induced acute renal failure in the rat.

Cited by 45 publications

References 13 publications

Long-Term Effects of Mild Oligonephronia Induced In Utero by Gentamicin in the Rat

Long-Term Effects of Mild Oligonephronia Induced In Utero by Gentamicin in the Rat

Properties of the Glomerular Barrier and Mechanisms of Proteinuria

Neutralization of Circulating Vascular Endothelial Growth Factor (VEGF) by Anti-VEGF Antibodies and Soluble VEGF Receptor 1 (sFlt-1) Induces Proteinuria

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