Characterization of renal injury initiated by immunization of rats with heparan sulfate

Abstract

To investigate the role of antibody to heparan sulfate (HS) in the development of glomerular injury, male Lewis rats were immunized with HS and compared with unimmunized controls. In HS-immunized rats circulating antibodies that bound to renal basement membranes, an increase in serum creatinine (0.8 mg/dl versus 0.6 in controls P less than 0.01), and a 40% decline in creatinine clearance developed. In no animal did abnormal proteinuria develop. By histologic examination there was glomerular and interstitial capillary engorgement with erythrocytes, modest infiltration by polymorphonuclear leukocytes, and no proliferation of intrinsic glomerular cells. Immunofluorescence microscopy demonstrated deposits of rat IgG along the glomerular basement membrane. Bowman's capsule, and peritubular capillaries. Electron-microscopic examination revealed capillary engorgement with erythrocytes that appeared adherent to each other and contained entrapped areas of rarefied material. These observations demonstrate that binding of antibody to HS in the glomerulus induces a mild inflammatory reaction and a reduction in glomerular filtration rate, but no abnormal proteinuria.