Pathogenicity of cationized albumin in the dog: renal and extrarenal effects.
The effects of 21 cationized serum albumin samples of various degrees of cationization on renal function were studied in the dog. The samples were perfused intra- aortically to obtain preferential perfusion of the left kidney in 25 dogs. Standard clearance techniques were used, associated in six dogs with sieving studies of 125I-labelled polyvinylpyrrolidone (125I-PVP) and with an extensive morphological study in 15 dogs. Renal effects were observed. (a) Renal effects in left kidneys. The perfusion with weakly cationized albumin (group 1) produced moderate proteinuria associated with the deposition of cationized albumin on the anionic sites of the basement membrane. Glomerular filtration rate (GFR) was unaltered. Perfusion with highly cationized samples (group 2) produced more severe proteinuria and a significant decrease in GFR. Glomerular permeability to 125I-PVP increased. Perfusion with the four samples of highest pI (group 3) was followed by anuria. (b) Renal effects in right kidneys. A retarded mild proteinuria appeared only in group 2 and group 3 animals without alteration of GFR. All the kidneys (group 1 included), with the exception of two (group 3), showed deposition of the protein in the anionic sites. The following extrarenal effects were observed essentially in group 2 and group 3 animals: erythrocyte agglutination and haemolysis, platelet aggregation and thrombocytopenia, and a decrease in plasma fibrogen level due to fibrinogen precipitation. These effects produced progressive obstruction in the glomerular capillaries, thus explaining the occurrence of anuria. The structural damage in group 2 and group 3 left kidneys bears remarkable resemblance to that observed in the fulminant form of the human so-called 'haemolytic-uraemic syndrome'. The neutralization alone of the fixed negative charges in the glomerular wall appears to produce only mild proteinuria, whereas the various extrarenal effects combine to produce more severe proteinuria associated with functional alteration and vascular obstruction.
D058186:Acute Kidney Injury / Q000139:chemically induced; D000818:Animals; D002412:Cations; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced; D004285:Dogs; D004903:Erythrocyte Aggregation / Q000187:drug effects; D005340:Fibrinogen / Q000032:analysis; D066298:In Vitro Techniques; D007526:Isoelectric Point; D007668:Kidney / Q000187:drug effects* / Q000648:ultrastructure; D007677:Kidney Function Tests; D008854:Microscopy, Electron; D010976:Platelet Count; D011507:Proteinuria / Q000139:chemically induced; D012709:Serum Albumin / Q000633:toxicity*
D002412:Cations; D012709:Serum Albumin; D005340:Fibrinogen