Donald B. Kaufman

The pathogenesis of the renal lesion in a patient with Streptococcal disease, infected ventriculoatrial shunt, cryoglobulinemia and nephritis

Abstract A case of acute poststreptococcal glomerulonephritis followed by shunt nephritis is presented. The patient manifested both persistent hypocomplementemia and cryoglobulinemia. Investigations into the nature of the glomerular deposits revealed the deposition of a staphylococcal antigen and immunoglobulin G (IgG) and β 1 C globulin in a nodular pattern. No immunopathologic role for the cryoglobulins could be demonstrated, and Streptococcal products could not be identified by immunohistologic methods. The evidence supports a circulating bacterial antigen-antibacterial complex in pathogenesis, and thus the identification of an antigen in human immune complex renal disease.

Diffuse familial nephropathy: a clinicopathological study.

Renal tissue specimens from 23 patients with hereditary nephritis were studied by light and immunofluorescent microscopy. The patients were followed from 1 to 11 years and had ophthalmologic, audiologic, and renal function tests performed periodically. Hematuria was present in all patients and was the usual presenting complaint. Proteinuria was present in 71 per cent and hearing loss in 42 per cent. Three women developed renal failure. There was no correlation between morphology, renal function, and urinary sediment except in patients with renal failure. The morphologic picture was one of slow progression, with a mixed glomerular and interstitial nephritis. Glomerular basement membrane thickening was the earliest and most common lesion. By studying serial biopsies of 15 patients, the intermediate histologic lesions were observed for the first time.

Secretory IgA in Urinary Tract Infections

Secretory IgA, measured by radial immunodiffusion, was compared in the urine of children with chronic and recurrent non-obstructive urinary tract infections with that in normal children. IgA, IgG, and IgM were also measured. Absent and low levels of IgA(s) were found in both groups; however, the mean levels of IgA(s) were significantly higher in the infected group compared with normals—3·3 to 0·78 mg./24 hours, respectively. Secretory IgA was found to be locally produced in the bladder. It is suggested that IgA(s) levels reflect an antibody response to infection.

ALTERATION OF THE CHEMICAL COMPOSITION OF HUMAN IMMUNOGLOBULIN G BY STREPTOCOCCUS PYOGENES

Summary Incubation with Streptococcus pyogenes type 12 was shown to lead to marked alterations of the fucose, galactose, and total hexose content of human immunoglobulin G (IgG). Immunological studies showed at least partial identity of this altered IgG and normal IgG. Streptococcal antigen was not found in the altered immunoglobulin. We suggest that if such alterations occurred in vivo, the altered immunoglobulin might become autoimmunogenic or might possess the biological properties of immune complexes and thus be of immunopathological significance in post-streptococcal glomerulonephritis.

Glomerular localization of fibrinogen—Linicopathologic, prognostic and therapeutic considerations☆

Abstract Immunofluorescent studies were performed on 250 percutaneous renal biopsies on patients with various renal diseases. The deposition of fibrinogen was correlated with the presence of glomerular I g G and β 1 C globulin, duration, clinical manifestations, chronicity and prognosis of the disease, and light microscopic changes. Fibrinogen was localized frequently in S.L.E., homotransplant rejections, the nephrotic syndrome secondary to membranous, proliferative, mixed and focal disease, acute post-strepto-coccal glomerulonephritis, some collagen vascular diseases and anaphylactoid purpura. Fibrinogen was not localized in asymptomatic proteinuria, hereditary nephropathy, Wegeners granulomatosis, pyelonephritis, nephronopthisis, gouty nephropathy, gold nephropathy or hemosiderosis. Correlation with I g G and β 1 C deposition was inconsistent as were the degree of proteinuria, level of renal function, prognosis, and light microscopic findings. This was particularly true in diseases studied early after the onset of symptoms and those on antimetabolite therapy. Localization of fibrinogen was most valuable in post renal transplant patients. We suggest that combined with other parameters of renal function and morphology, fibrinogen localization may aid as a guide for the use of anticoagulants in renal disease. Larger longitudinal studies may determine whether fibrinogen localization can be of use in predicting chronicity and response to anticoagulant therapy.

Excretory urography following percutaneous renal biopsy in children and adolescents.

Excretory urograms were obtained in 40 children and adolescents before and after percutaneous renal biopsy. The postbiopsy urograms were positive in approximately one-fourth of the patients, most of whom had corresponding positive clinical findings. In three-fourths of the patients there were no clinical indications of complications, and the postbiopsy urograms were also negative. Routine postbiopsy excretory urography is not recommended, but, in the presence of even mild symptoms of pain, hematuria, or decreasing hematocrit, a postbiopsy study may be of value in detecting the potential of later complications.

Chemical and Immunologic Characteristics of Glomerular Basement Membrane Fragments in Rat Urine

Glomerular basement membranne (GBM) is composed of a collagen-like component and a carbothydrate rich glycoprotein. GBM fragments have been found in the urine of normal and nephritic man and experimental animals. This study was designed to isolate, purify and chemically and immunologically characterize GBM fragments of rat urine.A glycoprotein, the major protein innormal rat urine (MUP), was isolated by DEAE ion excahange chromatography and purifed by gel filtration on Sephadex G 200. MUP was shown to be a cabohydrate rice glycoprotein with an amino acid content similar to the non-collagen component of GBM. Fluorescein conjugated antisera could be absorbed with rat GBM, rat glomeruli, 8 M urea solubilized GBM but not by rat collagen or the collagen component of GBM. The glycoprotein is similar to albumin in molecular size. In experimental nephrosis, the excretion of MUP is increased and the content of hexose altered.

The effects of azathioprine on experimentally induced immune complex renal disease in rabbits

Abstract To evaluate the effects of azathioprine on immune complex renal disease, soluble complexes of BSA-rabbit anti-BSA were injected into 5 groups of rabbits. Groups I, II and III received daily injections of azathioprine 1 mo prior to the administration of complexes. Group II continued to receive drug therapy for 1 subsequent mo. Groups IV and V received soluble complexes only. The groups were sacrificed at different intervals, and the kidneys were evaluated for morphologic and immunopathologic changes. Serologic and urinary protein studies were also done. No beneficial effects of therapy were noted on the development of glomerulonephritis in any experimental group. Continuous therapy appeared to have an adverse effect on the course of the glomerular lesions, with 44% of the continuously treated animals developing moderate disease as opposed to 5% of the pretreated and 7.1% of the control rabbits. The incidence of anaphylactic shock was diminished in the azathioprine treated animals. Immunohistologic localization of rabbit IgG was present in most animals, while B 1 C was virtually absent. The presence of BSA was variable but notably absent in the long term azathioprine treated rabbits.