Characterization of nephropathy induced by immunization with high molecular weight dextran

Background. Injection of DEAE dextran into Lewis ratscan produce proteinuria and has been reported as a model of IgAnephropathy. Methods. Cationic diethyl aminoethyl(DEAE) dextran of molecular weight 500 KDa was injected into male Lewisrats. After a pre-immunization period of 3 weeks, the animals were dividedinto two groups: group 1 (n=14) received daily i.v. injections of 3.5 mg ofantigen, group 2 (n=14) was injected with 1.5 mg three times per week for atotal period of 6 weeks. I.v. treatment was initiated with graduallyincreasing doses of DEAE dextran in both groups for 1 week, after which themaintenance dose was reached. Results. We observed theappearance of proteinuria in a nephrotic range after 5 weeks of i.v.injections in group 1 (urinary excretion: 332±83 mg/24 h,controls: 53±14 mg/24 h). In group 2, the proteinuria was almostequal to protein excretion of healthy rats of the same weight(67±20 mg/24 h). The serum and urine creatinine were normal. Bylight microscopy of kidney biopsies, the presence of focal and segmentalproliferation of mesangial cells after 6 weeks of i.v. injections wasidentified. Immunohistochemistry revealed no deposition of IgA, IgM, IgG,or C3. Using anti-ED1 antibodies, there was no evidence of interstitialinfiltration of monocytes/macrophages after 6 weeks of i.v. injections.Staining for proliferating cell nuclear antigen (PCNA) did not show thepresence of proliferating cells either in glomeruli or in the interstitium.Staining with FITC-WGA lectin revealed focal and segmental loss of thenegative charge in the capillary wall. By electron microscopy there wasdeposition of dextran in the basal membrane and segmental and focal damageof the podocyte foot processes. As the chemokine RANTES may be involved inglomerular injury, we examined the kidneys of proteinuric andnon-proteinuric rats for the presence of RANTES. By indirectimmunofluorescence only the proteinuric rats showed RANTES deposition inmesangium. Conclusions. Injection of rats with DEAEdextran leads to dose-dependent proteinuria without deposition of immunecomplexes but with podocyte damage. This is associated with localexpression of the chemokine RANTES which may play a role in proteinuria ofglomerular disease.