Acute reversible proteinuria induced by infusion of the polycation hexadimethrine

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. Proteinuric aigue reversible determinee par la perfusion du polycation hexadimethrine. Afin de verifier l'hypothese selon laquelle la neutralisation des polyanions du filtre glomerulaire in vivo determine la perte de la permselectivite dependant de la charge, nous avons perfuse le polycation hexadimethrine (HDM) par voie intraveineuse a des rats. Une proteinurie massive est apparue, apres un intervalle libre de 30 a 50 minutes, et a disparu quand la perfusion a ete arretee. L'administration simultanee d'heparine empeche la proteinurie. Les proteines urinaires ont ete examinees par immunoelectrophorese, focalisation iso-electritrique avec immunofixation, et electrophorese en polyacrylamide. La proteine dominante etait l'albumine de rat, mais il y avait aussi de grandes quantites d'IgG intacte de rat. L'HDM etait lie aux sites connus des polyanions glomerulaires dans la lamina rarae de la membrane basale et sur les cellules epitheliales du glycocalice. En meme temps que cette liaison on a observe des anomalies reversibles des cellules epitheliales semblables a celles observees au cours de la neutralisation in vitro des polyanions glomerulaires. Il n'a pas ete observe d'autre anomalie histologique, a part la presence de cylindres proteiques. Ces resultats apportent la preuve directe de ce que la neutralisation des polyanions glomerulaires in vivo a pour consequence une proteinuric massive. L'apparition de quantites importantes d'IgG de rat dans l'urine implique que des anomalies de taille surviennent en meme temps que celles de la permselectivite dependant de la charge, ce qui suggere que les polyanions du filtre glomerulaire peuvent etre importants dans le maintien de la structure et des fonctions.