Membranous glomerulonephritis in the mouse

Membranous glomerulonephritis in the mouse. Glomerulonephritis was induced in C57.B110 mice by a single injection of rabbit IgG against homologous, pronase-digested, renal tubular antigens. The heterologous phase was characterized by a transient increase of glomerular permeability with fixation of rabbit IgG to the capillary walls, in a linear or fine-granular pattern, and to the brush borders of the proximal tubuli. The autologous phase was marked by the immune response to the injected protein, during which subepithelial immune deposits, consisting of mouse IgG1, rabbit IgG, and mouse C3 developed. Small amounts were still present at 1 year after the injection of antiserum. The antibody response of the mice correlated with the development and resolution of the deposits. None of the mice developed a nephrotic syndrome. Control mice treated with normal rabbit IgG did not show immune deposits in their kidneys at any stage despite a comparable antibody response to rabbit IgG. Immunoelectronmicroscopy showed that the rabbit antibodies fixed directly to an antigen in the cell membrane of the glomerular visceral epithelium. It seems, therefore, likely that in situ formation of subepithelial immune complexes occurred in the autologous phase by fixation of mouse immunoglobulins to rabbit IgG already present in the glomerular wall.Glomérulonéphrite extra-membraneuse chez la souris. Une glomérulonéphrite a été induite chez des souris C57.B110 par une injection unique d'IgG de lapin contre des antigènes tubulaires rénaux homologues, digérés par de la pronase. La phase hétérologue était caractérisée par une augmentation transitoire de la perméabilité glomérulaire avec fixation d'IgG de lapin aux parois capillaires, d'une façon linéaire ou finement granuleuse, et aux bordures en brosse des tubules proximaux. La phase autologue était marquée par la réponse immune à la protéine injectée, pendant laquelle des dépôts immuns sous-épithéliaux, consistant en de l'IgG1 de souris, de l'IgG de lapin et du C3 de souris, se sont développés. Il en restait encore de faibles quantités 1 an après l'injection de l'antisérum. La réponse anticorps des souris était corrélée avec le développement et la disparition des dépôts. Aucune des souris n'a développé de syndrome néphrotique. Les souris contrôles traitées avec de l'IgG de lapin normal n'ont pas eu de dépôts immuns dans le rein à aucun stade, malgré une réponse anticorps aux IgG de lapin comparable. La microscopie immuno-électronique a montré que les anticorps de lapin se fixaient directement à un antigène situé sur la membrane des cellules de l'épithélium viscéral glomérulaire. Il semble donc probable que la formation in situ de complexes immuns sous-épithéliaux est survenue à la phase autologue par fixation d'immunoglobulines de souris à de l'IgG de lapin déjà présente dans la paroi glomérulaire

Evidence for renal vasodilation in pre-dialysis patients during correction of anemia by erythropoietin

Evidence for renal vasodilation in pre-dialysis patients during correction of anemia by erythropoietin. Results from animal experiments have suggested that treatment with recombinant human erythropoietin (rHuEPO) causes changes in renal hemodynamics which are detrimental to renal function. Therefore, the effects of correction of the anemia by rHuEPO on glomerular filtration rate (GFR; inulin clearance) and effective renal plasma flow (ERPF; PAH clearance) were studied in eight pre-dialysis patients. The studies were done before (Hct 0.24 ± 0.05 liter/liter) and at 89 ± 19 days after the start of rHuEPO therapy (Hct 0.39 ± 0.03 liter/liter). To further evaluate the effects of ACE inhibition, 25 mg of captopril was given orally after baseline values had been obtained. Baseline GFR, renal blood flow (RBF) and filtration fraction (FF) did not change during rHuEPO therapy. At low hematocrit (Hct) captopril induced a significant increase in ERPF and RBF, and a decrease in MAP. After correction of the hematocrit the blood pressure lowering effect of captopril remained unchanged. However, captopril no longer induced changes in ERPF and RBF. We conclude that the increase in hematocrit had no adverse effects on GFR. The results suggest that changes in hematocrit may influence the effects of ACE inhibition on efferent vascular resistance. Therefore, the hematocrit should be taken into account when evaluating studies on the effects of ACE inhibition in the progression of chronic renal failure