Byron P. Croker

Fate Of Four Cadaveric Donor Renal Allografts With Mesangial Iga Deposits

In the course of routine pretransplant cadaveric donor kidney biopsy examination, specimens from two donors were found to exhibit intense mesangial localization of IgA by immunofluorescence, with the presence of large immune complex-type deposits in these areas confirmed ultrastructurally. Both kidneys from each donor were transplanted with the ultimate result that three of the four kidneys underwent early irreversible rejection and were removed within 3 months, while the fourth kidney has maintained normal function for a period of 8 months. Morphological and immunofluorescent evaluation of the rejected kidneys at the time of nephrectomy showed minimal residual IgA mesangial deposits, but all had changes indicative of severe acute allograft rejection. These findings suggest that glomerular lesions involving mesangial IgA deposition can resolve fairly quickly following transplantation, but that the risk of irreversible acute rejection might be greater in the recipients of such kidneys.

Evaluation of recurrent glomerulonephritis in kidney allografts

Abstract The clinical records and biopsy and nephrectomy specimens from 320 patients treated at the Duke University Medical Center between 1965 and 1977 were examined to determine the type and incidence of recurrent glomerulonephritis in the allograft. The diagnosis of recurrent disease required that the histopathologic features of the transplanted kidney resemble those of the diseased native kidney by immunofluorescence and light and electron microscopy. Of 204 patients with tissue available for evaluation from both the native and the transplanted kidney, 117 had some form of chronic glomerulonephritis. Of the 117, there were 61 whose disease could be subclassified further. Idiopathic membranous glomerulonephritis was documented in seven patients, IgA nephropathy in five, focal glomerular sclerosis in 20, type 1 membranoproliferative glomerulonephritis in 16, type 2 membranoproliferative glomerulonephritis in two, proliferative glomerulonephritis in five, crescentic proliferative glomerulonephritis in four and anti-glomerular basement membrane disease in two. In this group of 61, there were 19 patients with 21 allografts in which there was evidence of recurrent glomerulonephritis including four each with idiopathic membranous glomerulonephritis and focal glomerular sclerosis, seven with type 1 membranoproliferative glomerulonephritis, two each with type 2 membranoproliferative glomerulonephritis and anti-glomerular basement membrane disease and one each with IgA nephropathy and crescentic proliferative glomerulonephritis. There were 104 living related donor kidneys grafted into patients with chronic glomerulonephritis, and 78 had tissue available for evaluation. In this group, 15 patients had 16 grafts with recurrent glomerulonephritis. There were 55 cadaveric donor kidneys transplanted into patients with chronic glomerulonephritis, and 39 had tissue available for evaluation. In this group, there were five examples of recurrent glomerulonephritis. Thus, recurrent glomerulonephritis can occur in a variety of histologic subtypes, and in this study population, recurrent glomerulonephritis was more common in allografts from living related donors.

Clinical and pathologic features of polyarteritis nodosa and its renal-limited variant: Primary crescentic and necrotizing glomerulonephritis

This study supports the concept that primary necrotizing and crescentic glomerulonephritis is a kidney-limited form of polyarteritis nodosa. Thirty-four patients with necrotizing and crescentic glomerulonephritis were divided into three groups based on the presence or absence of systemic vasculitis as determined by clinical or histologic criteria. Laboratory studies demonstrated elevated erythrocyte sedimentation rates, anemia, mild eosinophilia, hematuria, and proteinuria in patients in each group; there were no significant differences in these data between the groups, however. Complement levels and antinuclear antibody screens were normal. Mean serum creatinine levels were markedly elevated but fell by a factor of two following therapy. There was a higher morbidity in the patients with kidney-limited disease. This was attributable to a higher percentage of these patients having no symptoms and presenting for medical care only after they were in chronic renal failure. Most patients not experiencing chronic renal failure were treated with cyclophosphamide and prednisone, which seemed effective in this retrospective study.

Polypoid tumor of the esophagus

Five cases of an uncommon esophageal tumor consisting of a mucosal squamous cell carcinoma that surrounds a polypoid mass of spindle cells were examined. The spindle cell component was composed of elongated cells with blunt nuclei, admixed with multinucleated giant cells. Reticulin fibers enveloped individual cells, and abundant collagen was present. Thirteen to 69 mitotic figures occurred per 10 high-power fields. Electron microscopy showed dilated cisternae of rough endoplasmic reticulum and peripheral intermediate filaments within the cytoplasm. Intermediate-type junctions (zonulae adherens) and subplasmalemmal linear densities connected some cells. No tonofibrillar bundles or desmosomes (maculae adherens) were present. Immunoperoxidase stains detected no keratin in the spindle cells. Alpha-1-antichymotrypsin and alpha-1-antitrypsin were in the spindle cells in five of five and three of five cases, respectively. The absence of desmosomes, tonofibrillar bundles, and keratin and the presence of alpha-1-antitrypsin and alpha-1-antichymotrypsin favor fibrohistiocytic differentiation of the spindle cell component.

Systemic kappa light-chain deposition. An ultrastructural and immunohistochemical study.

This report describes the pathology of kappa light-chain deposition in a 55-year-old patient who presented with respiratory insufficiency and hepatomegaly. Biopsies of lung and liver showed PAS-positive deposits which did not stain with congo red, crystal violet, or thioflavin-T. By indirect immunoperoxidase techniques, the deposits were composed of kappa light-chain immunoglobin. Electron microscopy revealed granular and fibrillar electron-dense material which lacked the characteristics of amyloid. Subsequent clinical studies showed this patient had a plasma cell dyscrasia. These data show that kappa light-chain deposition is not limited to the kidney, and that the first manifestation of a plasma cell dyscrasia may be systemic deposits of light chain. These deposits can be distinguished from amyloid by their immunochemical, tinctorial, and ultrastructural appearance.

In vivo tumor localization using tumor-specific monkey xenoantibody, alloantibody, and murine monoclonal xenoantibody.

Specific in vivo localization of antibodies reactive with human melanoma cell membrane tumor associated antigens (TAA) has been attempted using congenitally athymic nude mice bearing subcutaneous human melanoma tumor xenografts as the experimental model. IgG fractions were prepared from each of several immune and control sera. Antimelanoma antibody sources included human alloantibody obtained from melanoma patients immunized against allogeneic melanoma cells, a monkey antiserum raised by immunization against a single human melanoma cell line, and a murine monoclonal antimelanoma antibody-secreting hybridoma cell line. Localization of these radiolabeled antibodies and of control IgG preparations to tumor tissue was determined by whole body scintigraphy and by differential tissue counting. Compared with the different control IgG preparations, each of the antimelanoma IgG preparations exhibited significant specific accumulation within the melanoma tissue. However, variation existed in the ability of each antimelanoma IgG to tumor preparation to localize despite attempts to control model parameters such as tumor source, vivo passage number and mass. This variation appears to reflect basic biologic differences between tumors in different animals and possibly differences in the antigen-binding capacities of each IgG preparation following radioiodination. This technique for tumor localization is very promising and has obvious potential for clinical application

The possible occurrence of staphylococcal postinfectious glomerulonephritis in a renal allograft.

A 38-year-old male with a 5-year history of dialysisdependent renal failure secondary to membranoproliferative glomerulonephritis, type I, received a cadaveric renal allograft from a 51-year-old male dying from acute trauma. A pretransplant biopsy of the donor kidney revealed no glomerular disease. One month after transplantation, the patient was discharged with a stable creatinine of less than 2.0 mg/dl, but subsequently developed positive urine cultures for Staphylococcus aureus and Escherichia coli and eventually underwent transplant nephrectomy. Blood cultures were positive postoperatively for S. aureus, and examination of the transplant nephrectomy showed ultrastructural, histological, and immunofluorescent findings characteristic of postinfectious glomerulonephritis. While numerous types of glomerular disease have been reported in kidney transplants, this report represents the first case suggestive of bacterial postinfectious type glomerulonephritis we have seen occurring de novo in a renal allograft.

IMMUNOLOGICAL CONSEQUENCES OF TRANSPLANTING RAT INSULINOMAS

We investigated the genetics of transplanting a NEDH rat insulinoma in various donor-recipient combinations. The insulinoma survived indefinitely when it was transplanted in the NEDH strain. Mean survival times of 8.6 ± 1.2 and 3.3 ± 1.0 days were recorded in allogeneic and xenogeneic combinations, respectively. No prolongation of mean survival time was found when the rat insulinoma was first passed through the athymic nude mouse and then transplanted as either an allograft or xenograft. The findings of the major histocompatibility antigen (Ag-B7) on the original insulinoma and the tumor that had been passed through the nude mouse demonstrates no demonstrable loss of transplantation antigens during passage.

Retinoblastoma Metastatic to Bone Marrow A Case with Florid Spread

A 28-month-old white male, 7 months status postenucleation for retinoblastoma, presented with lethargy, irritability, anemia, and thrombocytopenia. Bone marrow examination revealed almost total replacement of marrow elements with clumps of small round basophilic cells. Electron microscopic study of the marrow revealed clumps of cohesive tumor cells with intermediate junctions, establishing a diagnosis of metastatic retinoblastoma.

1482 INTERACTIONS OF HUMAN, CULTURED KIDNEY CELLS WITH THE COMPLEMENT (C) SYSTEM

Previously we have shown that C activation takes place when heat-killed, cultured human kidney cells are incubated in normal human serum. C activation initiated by 0.5 × 107 cells/50 μl permitted moderate C4, C2, C3 and C5 consumption of hemolytic activity without detectable loss of Cl and no reduction in C6 activity. At 2 × 107 cells/50 μl serum, some loss of C1 and C6 hemolytic activity was noted. C4 and C2 consumption could not be prevented by blocking primary C pathway through prior EGTA chelation of serum.Both living and heat-killed kidney cells were incubated with normal serum and then examined for surface bound C components using immunofluorescence techniques. The heat-killed kidney cells were strongly positive for C3 which was distributed in a diffuse, speckled pattern over the entire cell surface . Dead cell suspensions also showed weak IgG and Clq immunofluorescence but were negative for surface albumin, C5 and β1H. In contrast, living cell suspensions treated in a similar manner showed only occasional cells immunofluorescent positive for C3, IgG or Clq and all cells were negative for albumin, C5 and β1H. Viability stains run concurrently revealed that the few C3 positive cells in living cell suspensions belonged to the small, nonviable cell subpopulation. These data indicate that dead kidney cells can initiate limited C activation resulting in preferential C3b opsonization of dead, but not living cells.