Laboratory Investigation

Kidney International (1981) 20, 7–17; doi:10.1038/ki.1981.98

Acute reversible proteinuria induced by infusion of the polycation hexadimethrine

Lawrence G Hunsicker1, Thomas P Shearer1 and Sandra J Shaffer1

1Departments of Internal Medicine, University of Iowa Medical College and Veterans Administration Medical Center, Iowa City, Iowa

Correspondence: Dr L G Hunsicker, VA Medical Center, Building 3, Iowa City, Iowa 52240, USA

Received 12 May 1980; Revised 18 September 1980.

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Abstract

Acute reversible proteinuria induced by infusion of the polycation hexadimethrine. To test the hypothesis that neutralization of polyanions of the glomerular filter in vivo will lead to loss of charge-dependent glomerular permselectivity, we have infused i.v. the polycation hexadimethrine (HDM) into rats. Heavy proteinuria resulted after a lag period of 30 to 50 min, and it resolved when the infusion was stopped. Concurrent administration of heparin prevented the proteinuria. Urinary proteins were examined by Immunoelectrophoresis, isoelectric focusing with immunofixation, and sodium dodecylsulfate polyacryl-amide electrophoresis. The major protein was rat albumin, but there were also large quantities of intact rat IgG. HDM was bound at known sites of glomerular polyanion in the laminae rarae of the basement membrane and on the epithelial cell glycocalyx. Associated with this binding were reversible abnormalities of the epithelial cells similar to those seen during in vitro neutralization of glomerular polyanion. Aside from proteinaceous tubular casts, no other histologic abnormality was noted. These studies provide direct evidence that neutralization of glomerular polyanions in vivo results in heavy proteinuria. The appearance of substantial quantities of rat IgG in the urine implies that abnormalities of size as well as charge-dependent permselectivity occur, suggesting that the polyanions of the glomerular filter may be important in maintaining its structure as well as its function.

Protéinuric aiguë réversible déterminée par la perfusion du polycation hexadimethrine. Afin de vérifier l'hypothèse selon laquelle la neutralisation des polyanions du filtre glomérulaire in vivo détermine la perte de la permsélectivité dépendant de la charge, nous avons perfusé le polycation hexadimethrine (HDM) par voie intraveineuse à des rats. Une protéinurie massive est apparue, après un intervalle libre de 30 à 50 minutes, et a disparu quand la perfusion a été arrêtée. L'administration simultanée d'héparine empêche la protéinurie. Les protéines urinaires ont été examinées par immunoélectrophorèse, focalisation iso-électritrique avec immunofixation, et électrophorèse en polyacrylamide. La protéine dominante était l'albumine de rat, mais il y avait aussi de grandes quantités d'IgG intacte de rat. L'HDM était lié aux sites connus des polyanions glomérulaires dans la lamina rarae de la membrane basale et sur les cellules épithéliales du glycocalice. En même temps que cette liaison on a observé des anomalies réversibles des cellules épithéliales semblables à celles observées au cours de la neutralisation in vitro des polyanions glomérulaires. Il n'a pas été observé d'autre anomalie histologique, à part la présence de cylindres protéiques. Ces résultats apportent la preuve directe de ce que la neutralisation des polyanions glomérulaires in vivo a pour conséquence une proteinuric massive. L'apparition de quantités importantes d'IgG de rat dans l'urine implique que des anomalies de taille surviennent en même temps que celles de la permsélectivité dépendant de la charge, ce qui suggère que les polyanions du filtre glomérulaire peuvent être importants dans le maintien de la structure et des fonctions.

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