The main purpose of this article is to investigate the immunological back ground in the pathogenesis of human chronic glomerulonephritis. At the first step, the existence of cross-antigenisities among the mammalias especially between human and rat renal basement membranes was proven through the following experimental evidence that in vivo administrated anti human renal basement membrane rabbit serum to rats was fluorescent microscopically found to be immediately fixed linearly along the rat renal glomerular basement membranes, forming regional focal immune complexes, and simultaneously focal glomerulonephritis was produced. The antigenic determinants in the glomerular capillary basement membrane at this occasion was thought to be located in trypsin or collagenase digestion resistant macro-molecular ingredients of the basement membrane. In the human chronic glomerulonephritic kidneys obtained at autopsies, fluorescent microscopical examinations revealed that IgG fraction was rarely but serum complement component was frequently bound linearly along the glomerular capillary basement membranes. On the contrary, the eluted materials from the chronic glomerulonephritic kidneys under acidic citric buffer contained IgG fraction in high percentages. Furthermore, such eluted IgG from the glomerulonephritic kidneys showed capacity to combine focally with rat glomerular capillary basement membranes, to form immune complexes and develop transient proliferative focal glomerulonephritis after in vivo administration to rats. The sera from the chronic glomerulonephritic cases or the eluted materials from several control kidneys which although contained some IgG fractions, revealed no such in vivo reactivities to rat renal glomeruli. From the above findings, it was thought that eluted IgG from the human chronic glomerulonephritic kidneys might have had in vivo glomerular basement membrane bound activity even in their own kidneys, although could not be demonstrated by immuno-fluorescent examination. Successively formed regional immune complexes might have given incessant pathogenic effects upon glomeruli, which led to progressive chronic glomerulonephritis. The autoimmune nature in pathogenesis of this disease could be well compared to that of the experimental nephrotoxic serum nephritis and furthermore, this pathogenic process was frankly represented clinically on the occurrence of proliferative glomerulonephritis in the transplanted kidneys to the chronic glomerulonephritic patients.

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To study the effect of renal ischemia on the progression of glomerulonephritis experimentally, Masuginephritis was induced in rabbits and four weeks later the left renal artery of each animal was constricted. Alteration of the kidneys were perused with biopsy- and autopsy-specimens up to twenty weeks after the clamp. Histologically, glomerular alterations could be deviled into five types (A-E) ; (A) of normal appearance, (B) with exudation and proliferation, (C) with ischemic alterations alone, (D) showing both proliferation and ischemia with capillary and capsular contact and (E) of hyalinization. In the constricted kidneys, the number of (A) was significantly less than the other side. There was a tendency to be " the longer the constricted duration, the more decreased the ratio of (A)". And (E) began to appear in four weeks after the operation, the rate of occurrence reaching 1.5-3 times of non-constricted sides, and the rate of (B) began to decrease from 8 th week after the operation. Different from non-clipped side, (C) developed early after the operation and increased to about 30% of total glomeruli, as well as (D), the maximal rate of which reached to 24% in 10 th weeks, gradually decreasing thereafter. (D) is characteristically found in the kidneys with severe ischemia and glomerular inflammatory changes and some of them, at least, are assumed to progress into hyalinization. Thus, renal' ischemia seems to accelerate the deterioration of the glomerular inflammatory lesions. Electron microscopic observation of (C) revealed prominent wrinkling of the capillary basement membrane and decreasing of mesangial matrix. By immunofluorescent studies, the brightness of capillary pattern of the glomeruli of the clipped kidneys was almost identical or less intensive than those of the non-clipped kidneys. These results suggest no participation of additional immune-mechanism in the deterioration of the glomerular changes. Though J-G indices in these glomeruli were variable, the indices of non-clipped were often larger than those of clipped kidneys.

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Experimental exacerbation was induced by means of nonspecific superimposition of serum sickness in rabbits with nephrotoxic nephritis. Rabbits were injected intravenously with 1.0 to 1.8 ml antirabbit kidney duck sera per kg body weight. Four to eight weeks after the first administration, they were injected intravenously with 200 mg bovine serum albumin per kg body weight. Control rabbits were only treated with the same amount of bovine serum albumin. The exacerbation was induced in most rabbits with nephrotoxic nephritis. The grade of exacerbation was parallel with the initial severity of renal damage. This study has clearified that the exacerbation of the nephritis was caused by the different agent from the initial one, even when given in small amount which could not damage the kidney of normal rabbits.

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