Lobular Glomerulonephritis Research Articles

Gamma G globulin subgroup composition of the glomerular deposits in human renal diseases.

36 renal biopsies from patients with nephritis were studied for glomerular localization of the heavy chain subgroups of immunoglobulin G (IgG or gammaG). The deposition pattern of these subgroups was selective and did not reflect the normal serum concentration of these proteins. gammaG2, which comprises 18% of normal serum gammaG, was the predominant or unique subgroup deposited in five cases of lupus nephritis and four biopsies with other forms of nephritis associated with granular gammaG deposits. gammaG3, which normally makes up only 8% of the serum gammaG, was the dominant subgroup seen in one biopsy of lobular glomerulonephritis. Patients with linear gammaG deposits generally had a selective absence of gammaG3 and often had large amounts of gammaG4 (normally 3% of the serum gammaG) deposited. The deposition of complement components C1q, C4, and C3 was variable. One biopsy had only gammaG2 and no complement components in the deposits and had no neutrophile leukocyte infiltration. This latter observation correlates well with the poor ability of gammaG2 to fix complement in vitro. Similarly, deposits containing large amounts of gammaG4, which does not fix complement, also tended to have less inflammatory infiltrate than deposits devoid of this subgroup. The selective deposition of monotypic or restricted gammaG subgroups on the glomerulus supports the likelihood that the gammaG represents antibody. The nature of the subgroup involved in the deposit may represent one variable in the determination of the inflammatory and morphological picture that evolves in human glomerulonephritis.

Transplantation of a paired organ, the kidney.

Transplantation of the kidney, at least between related donor-recipient pairs, is now a clinically feasible procedure. A recent analysis of more than 2000 human renal allografts reported to the Transplantation Registry indicated that the two-year survival rate for sibling donor-recipient pairs is approximately 80 per cent. The results of recent transplantations of cadaver kidneys shows a success rate comparable to that of open heart surgery for acquired valvular disease. I believe, therefore, that if a living, related donor is available, the results justify the transplantation of a kidney at an earlier stage than previously. Peripheral neuropathy and other irreversible consequences of advanced renal failure may thus be avoided. A number of immunological problems, however, still exist. The agents now available for immunosuppressive therapy (azathioprine, prednisone, and antilymphocyte globulin therapy) are tools not sharp enough for the job. At present there is no evidence that antilymphocyte globulin has significantly improved the results of kidney transplantation in humans, although it is unquestionably a potent immunosuppressive agent in the experimental animal. Moreover, these agents cause serious side effects: infection, failure of wound healing, enhancement of the growth of malignant tumors which have been inadvertently transplanted, and an increase in the incidence of malignant tumors of the lymphatic system. This latter complication was most dramatically pointed up by a recent communication from the Cleveland Clinic noting the appearance of a reticulum cell sarcoma at the site of injection of antilymphocyte globulin. Delayed damage to the renal allograft may also present serious problems. After a patient has apparently done well for a period of two or three years, the transplanted kidney may develop lesions of glomerular nephritis. In some cases this appears to be due to the development of the same disease that had destroyed the original kidneys of the recipient, while in other cases the lesions must be attributed to the rejection process. A dramatic illustration of the latter was a patient who developed typical lobular glomerulonephritis in a renal transplant without any history of renal disease. Allografting was necessitated in his case by the mistaken removal of a single ectopic kidney. Similar lesions also occur in the transplanted kidneys of normal rats. Enlargement and proliferation of endothelial and mesangial cells can be seen three to five days after transplantation. Glomerular capillaries are partially occluded at this time, and granular deposits of IgG and beta 1 C globulin on capillary walls and mesangial areas can be demonstrated by immunofluorescence. Deposits on the epithelial side of the basement membrane can be demonstrated by electronmicroscopy. Another type of lesion, also related to rejection, may occur in kidney transplants that have functioned well for long periods. Obliterative vascular disease may develop without glomerular lesions. Again, a study of the sequential events in the rat kidney may help explain this result. Numerous mononuclear cells

NEEDLE BIOPSY IN CHILDREN WITH NEPHROSIS

Needle biopsy of the kidney was done in 20 children with nephrosis for estimation of degree of glomerular damage in the early stage of the disease and of its change after intensive adrenal steroid therapy. The mean number of glomeruli per biopsy was 18.7 with a standard deviation of ±8.4 and a range of 6 to 42. Glomerular involvement was seen in 100% of cases and in 5 to 100% of nephrons in material obtained at biopsy. Thickening of capillary basement membrane was present in 90% of cases and 32.4% of glomeruli; cellular proliferation in 65% of cases and 17.3% of glomeruli; hyalinization in 55% of cases and 8.9% of glomeruli; and fibrosis in 65% of cases and 12.8% of glomeruli. Lesions of various types were simultaneously present in most cases, but thickening of the capillary basement membrane was the predominant one. The nephrotic syndrome was observed in cases having histologic changes similar to those described as membranous, chronic azotemic, proliferative and lobular glomerulonephritis. Adrenal steroid therapy was given to induce a complete clinical-biochemical remission of the nephrotic syndrome. It occurred, usually but not always after the appearance of induced Cushing's syndrome, and was observed in 81.2% of children treated with adrenal steroids. Histologic improvement was observed in 90% of patients who had biopsy taken before and after therapy. Four patients of the total group (20%) showed a marked decrease of glomerular lesions. Administration of a maintenance dose of steroid hormone was necessary for prolonging biochemical remission of the nephrotic syndrome. Administration of prednisone seemed to decrease cellular proliferation and to arrest the progress from thickening of capillary basement membrane to obliteration of the glomerular capillary. The impression was gained that clinicalbiochemical and anatomic improvement of the nephrotic syndrome was not permanent unless spontaneous healing occurred, and that longer observation is required to evaluate the effect of prednisone.

ROLE OF GAMMA GLOBULINS IN PATHOGENESIS OF RENAL LESIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS AND CHRONIC MEMBRANOUS GLOMERULONEPHRITIS, WITH AN OBSERVATION ON THE LUPUS ERYTHEMATOSUS CELL REACTION

Utilizing the fluorescent antibody method for the histologic demonstration of localized gamma-globulins, we have made the following observations (in contradistinction to the lack of such findings in a variety of normal and pathologic, control kidneys). In systemic lupus erythematosus (a) gamma-globulins were localized in the thickened capillary walls, the "wire-loop" lesions, and the so called "hyaline thrombi" in glomeruli; (b) these sites of localization of gamma-globulins were correlated to a considerable degree with the pattern of accentuated eosinophilia of the glomeruli, as seen in hematoxylin-eosin sections, or with the pattern of PAS-positive areas in the glomeruli in sections stained with the periodic acid-Schiff reaction; (c) and gamma-globulins were localized rarely in large cytoplasmic granules in tubular epithelium and occasionally in glomerular capsular crescents, tubular protein casts, and inflammatory cells, particularly in the cytoplasm of cells identified as immature and mature plasma cells. In nephrotic glomerulonephritis (a) gamma-globulins were localized in the glomerular basement membrane and appertaining structures in chronic membranous glomerulonephritis; (b) gamma-globulins were apparently localized in the altered mesangium in chronic lobular glomerulonephritis; and (c) in the tubular protein casts, presumably representing abnormal glomerular filtrates, gamma-globulins were present in a lesser concentration and other serum proteins in a greater concentration than found in the glomeruli. In positive lupus erythematosus preparations the nuclei of leukocytes, while undergoing transformation and subsequent phagocytosis to form lupus erythematosus cells, were the sites of localization of gamma-globulin (presumably the lupus erythematosus factor) whereas in control preparations no nuclear localization of gamma-globulin occurred. These observations are discussed in relation to the pathogenesis of renal lesions in systemic lupus erythematosus, chronic membranous glomerulonephritis, and amyloidosis.