Anti-glomerular Basement Membrane Antibody-mediated Glomerulonephritis Research Articles

A case of triple pathology: seronegative anti-glomerular basement membrane antibody-mediated glomerulonephritis and membranous nephropathy in a patient with underlying diabetic kidney disease.

In diabetic patients with acute kidney injury (AKI), kidney biopsy often reveals non-diabetic kidney pathology. This case describes a patient with known Type 1 diabetes who presented with AKI, nephrotic syndrome and haematuria. Combination pathology of seronegative anti-glomerular basement membrane antibody-mediated glomerulonephritis (anti-GBM GN), membranous nephropathy (MN) and diabetic nephropathy (DN) was demonstrated. Strong linear GBM IgG-staining on biopsy with crescentic GN and clinical AKI led to a diagnosis of anti-GBM GN, although serum antibodies were not detectable. Features of DN, Kimmelstiel–Wilson nodules and albumin staining were also present, along with features of MN, such as subepithelial deposits on electron microscopy. Despite treatment with immunosuppression and plasmapheresis, there was no recovery of kidney function. Coexisting anti-GBM GN and MN is well recognized, but the concurrent diagnosis with DN has not been described.

Anti‐glomerular basement membrane antibody‐mediated glomerulonephritis combined with non‐fulminant acute viral hepatitis A

ABSTRACTAnti‐glomerular basement membrane antibody‐mediated glomerulonephritis (anti‐GBM Ab‐mediated GN) is a rare autoimmune disease, characterized by crescentic glomeruli and linear GBM staining with immunoglobulin G (IgG). Exposure to viruses can trigger the formation of autoantibodies to the GBM. We report the first case of anti‐GBM Ab‐mediated GN associated with hepatitis A virus (HAV) infection. Although the pathogenesis of HAV‐related anti‐GBM Ab‐mediated GN has not been documented, we suggest that the immune complexes produced by HAV infection might be deposited in the glomerular capillary walls and lead to immune complex‐mediated glomerular damage, resulting in exposure of the sequestered GBM antigens and the formation of anti‐GBM antibodies. Under immunosuppressive and intravenous cyclophosphamide therapy, his renal function has been improving without development of pulmonary symptoms.

Renal injury due to anti-glomerular basement membrane antibody-mediated glomerulonephritis without circulating antibody.

Renal injury due to anti-glomerular basement membrane antibody-mediated glomerulonephritis without circulating antibody.

Beneficial effect of human therapeutic intravenous immunoglobulins (IVIg) in mercuric-chloride-induced autoimmune disease of Brown-Norway rats

Administration of HgCl2 to the susceptible Brown-Norway (BN) strain of rats induces an autoimmune disease characterized by polyclonal B cell activation, increased serum levels of IgE and the occurrence of anti-glomerular basement membrane antibody-mediated glomerulonephritis. We have observed that the simultaneous administration to BN rats of normal human polyspecific immunoglobulins for therapeutic use (IVIg) with HgCl2 significantly decreased the occurrence and severity of proteinuria, and reduced serum IgE levels in diseased animals. Hypergammaglobulinaemia was potentiated in animals receiving HgCl2 and IVIg, compared with animals receiving HgCl2 alone. In vitro experiments indicated that F(ab')2 fragments from IVIg inhibited the binding to laminin of pathogenic anti-laminin antibodies from diseased rats, as did antibodies from the resistant Lewis strain of rats but not antibodies from susceptible BN rats. These observations suggest that IVIg may interfere with the immune regulatory mechanisms involved in mercury-induced autoimmune disease in an analogous fashion to the ability of IVIg to suppress the expression of certain pathological autoimmune responses in humans.

Sequential development of pulmonary hemorrhage with MPO-ANCA complicating anti–glomerular basement membrane antibody-mediated glomerulonephritis

We report a case of rapidly progressive glomerulonephritis caused by anti–glomerular basement membrane (anti-GBM) antibodies that progressed to end-stage renal disease in a 67-year-old woman with diabetes. Intensive combined immunosuppressive therapy with methylprednisolone bolus, oral prednisone, and cyclophosphamide led to negativity of anti-GBM antibodies but was not able to restore renal function. After 28 months of hemodialysis, the patient suddenly presented with pulmonary hemorrhage. In this setting, high levels of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) and negative anti-GBM antibodies were found. Therapy with oral prednisone and cyclophosphamide led to resolution of pulmonary hemorrhage and negativity of MPO-ANCA.

Heme oxygenase-1 induction attenuates inducible nitric oxide synthase expression and proteinuria in glomerulonephritis.

In glomerulonephritis, there is intraglomerular activation of inducible nitric oxide synthase (iNOS) leading to high output production of nitric oxide (NO). This can result in supraphysiologic amounts of NO and cause oxidative injury. It is unknown whether mechanisms of cellular defense against NO-mediated injury exist. Induction of the heme catabolizing enzyme heme oxygenase-1 (HO-1), which generates biliverdin, carbon monoxide (CO), and iron (Fe), may provide such a mechanism, as CO and Fe are two negative modulators of iNOS activity and expression. This study assessed whether upregulation of HO-1 by a specific inducer, hemin, negatively modulates iNOS expression and activity in anti-glomerular basement membrane antibody-mediated glomerulonephritis. Glomerular HO-1 expression in nephritic animals was upregulated by treatment with hemin (30 micromol/kg body wt). iNOS and HO-1 mRNA expression were assessed by reverse transcription-PCR of glomerular total RNA from nephritic animals or nephritic animals pretreated with hemin. iNOS activity in glomeruli was measured by assessing conversion of [14C] L-arginine to [14C] L-citrulline. HO-1 protein levels in glomeruli were assessed by Western blot analysis. The effect of hemin treatment on monocyte/macrophage infiltration was assessed by enumeration of ED-1-positive cells in nephritic glomeruli. iNOS and HO-1 were coinduced in nephritic glomeruli. Hemin treatment of nephritic animals resulted in upregulation of glomerular HO-1 levels and a two- to threefold reduction in glomerular iNOS mRNA levels. iNOS activity in glomeruli was significantly reduced in hemin-treated nephritic animals in which proteinuria was also attenuated without a change in monocyte/macrophage infiltration. Hemin (100 to 200 microM) also reduced iNOS protein levels and enzyme activity in cultured mesangial cells stimulated with cytokines. These studies demonstrate that in glomerular immune injury, hemin treatment upregulates glomerular HO-1 with an attendant downregulation of iNOS expression, and thus points to regulatory interaction between the two systems. The beneficial effect of hemin treatment on proteinuria could be linked to downregulation of iNOS.

Transfection of rat kidney with human 15-lipoxygenase suppresses inflammation and preserves function in experimental glomerulonephritis.

The human 15-lipoxygenase (15-LO) gene was transfected into rat kidneys in vivo via intra-renal arterial injection. Three days later, acute (passive) or accelerated forms of antiglomerular basement membrane antibody-mediated glomerulonephritis were induced in transfected and nontransfected or sham-transfected controls. Studies of glomerular functions (filtration and protein excretion) and ex vivo glomerular leukotriene B(4) biosynthesis at 3 hr, and up to 4 days, after induction of nephritis revealed preservation or normalization of these parameters in transfected kidneys that expressed human 15-LO mRNA and mature protein, but not in contralateral control kidneys or sham-transfected animals. The results provide in vivo-derived data supporting a direct anti-inflammatory role for 15-LO during immune-mediated tissue injury.

Occupational Solvent Exposure and Glomerulonephritis

We describe a patient who presented with renal failure after a one-year period of unprotected heavy occupational exposure to organic solvents. Renal biopsy results and serological findings were diagnostic of anti-glomerular basement membrane antibody-mediated glomerulonephritis. An analytic review of the literature revealed substantial evidence linking solvent exposure to the development of glomerulonephritis (GN), with seven of nine case-control studies demonstrating a statistically significant association. Odds ratios were reported by or could be calculated for six of these studies, and the five positive studies detected a 2.8- to 8.9-fold increased risk for GN among solvent-exposed individuals. The findings in several of these studies of dose-response relationships, the reports of variations in disease severity in relation to exposure intensity, and the absence of alternative explanations for the association provide additional supportive evidence for a solvent effect. In the majority of cases of anti-glomerular basement membrane antibody-mediated GN and other types of GN, there is no remarkable preceding exposure to organic solvents. However, we conclude that in the case presented herein and in cases of GN with similar exposure histories, solvent exposure may play a significant contributing role in the development of GN.

Glomerulonephritis associated with hydrocarbon solvents: mediated by antiglomerular basement membrane antibody.

In a retrospective analysis of 13 patients with antiglomerular basement membrane antibody-mediated glomerulonephritis, (autoimmune glomerulonephritis) eight patients were available for detailed personal interview. A history of extensive exposure to various industrial solvents was elicited in six of these eight patients. Often the exposure was to a vapor or fine mist of a heated solvent. Various petroleum products including paint removers, degreasing solvents, hair sprays, and painting solvents are suspected. Thus far, no specific component of these complex mixtures is implicated. On the basis of the studies in these patients, we propose that the first stage in the pathogenesis of autoimmune glomerulonephritis may be chemical injury to lung or kidney. According to this theory, the antibodies to glomerular basement membrane found in this syndrome would be considered a secondary response to chemical injury to lung or kidney basement membranes.