Concurrent anti-glomerular basement membrane disease and membranous glomerulonephritis: a case report and literature review

BACKGROUND: Anti-glomerular basement membrane disease (anti-GBM) is a relatively rare entity characterized by antibodies to collagen type IV of glomerular and alveolar basement membranes. The sequential or simultaneous presentation of anti-glomerular basement membrane disease with membranous glomerulonephritis has been infrequently described. CASE: We present the case of a 49-year-old man who had fatigue, flank pain, hematuria and renal failure. Serology was positive for anti-GBM antibodies; crescentic glomerulonephritis was seen on renal biopsy. Immunofluorescence and electron microscopy demonstrated evidence of both anti-GBM glomerulonephritis and membranous deposits. DISCUSSION: Simultaneous anti-GBM disease and membranous glomerulonephritis is the most common temporal presentation of this rare entity. However, cases of membranous glomerulonephritis preceding or following recovery from anti-GBM disease have been described. Study of such cases provides insight into pathophysiologic mechanisms, including the possibility of increased antigen synthesis, exposure of cryptic epitopes, and/or capping and shedding of antigen-antibody complexes, in analogy to Heymann nephritis.     

Non-Goodpasture anti-GBM antibodies in patients with glomerulonephritis

The sera of 206 consecutive patients with biopsy-proven glomerulonephritis were tested by ELISA for the presence of Goodpasture and non-Goodpasture anti-GBM antibodies. Antigens were solubilised from human GBM with purified bacterial collagenase and with 6 mol/l guanidine-HCl respectively. Only 12 sera reacted when collagenase-resistant GBM proteins were used as antigens in ELISA. Sera from two of these patients also reacted with the Goodpasture antigen, that is the globular domain of collagen IV, purified from collagenase extracts of GBM. These two patients had classical Goodpasture syndrome with linear crescentic nephritis. The other ten sera did not react with the Goodpasture antigen and immunofluorescence microscopy showed granular glomerular immune deposits. Antibodies against antigens present in 6 mol/l guanidine-HCl extracts of human GBM were much more frequent, particularly in lupus nephritis and IgA nephropathy, but relatively common also in patients with glomerulonephritis associated with systemic connective tissue and systemic vasculitic disorders. In contrast, these non-Goodpasture antibodies were only sporadic in primary forms of glomerulonephritis such as minimal-change nephropathy, membranous glomerulopathy, or acute post-infectious glomerulonephritis. The presence of circulating IgG, IgA or IgM antibodies against 6 mol/l guanidine-HCl extractable GBM antigens correlated with granular deposits of corresponding immunoglobulins in both mesangial and capillary loop regions of glomeruli, indicating a possible pathogenic role for non-Goodpasture anti-GBM antibodies in several forms of glomerulonephritis.     

Predominant role of FcgammaRIII in the induction of accelerated nephrotoxic glomerulonephritis

BACKGROUND: Nephrotoxic glomerulonephritis is induced by the administration of antibody against the glomerular basement membrane (GBM). We demonstrated previously that Fc receptors for immunoglobulin G (IgG) (FcgammaR) play crucial roles in the induction of accelerated nephrotoxic glomerulonephritis by using FcRgamma-deficient (-/-) mice. Since FcRgamma-/- mice lack the cell surface expression of two activating FcgammaRs, FcgammaRI and FcgammaRIII. The present study aims to identify the FcgammaR responsible for the induction of nephrotoxic glomerulonephritis. METHODS: Accelerated anti-GBM glomerulonephritis was induced in FcgammaRI-/-, FcgammaRIII-/-, and FcRgamma-/- mice by preimmunization with rabbit IgG followed by inoculation of rabbit anti-GBM antibody. Histologic analysis and immunostaining of renal sections were performed. RESULTS: FcgammaRI-/- mice as well as wild-type mice showed severe glomerulonephritis with hypernitremia by the administration of anti-GBM antibody. In contrast, FcgammaRIII-/- mice showed much milder renal involvement, similar to FcRgamma-/- mice. Histologically, FcgammaRI-/- mice showed intracapillary proliferation, glomerular thrombosis, and crescent formation, whereas FcgammaRIII-/- mice showed only glomerular hypercellular changes. The depositions of anti-GBM antibodies, autologous antibodies and complement C3 along the GBM were equally observed among all three FcR-/- mouse types by immunostaining. CONCLUSIONS: Accelerated nephrotoxic glomerulonephritis is induced predominantly through FcgammaRIII but not FcgammaRI.     

Antiglomerular basement membrane nephritis induced by IgA1 antibodies

A 62-year-old man was admitted for acute renal failure due to crescentic rapidly progressive glomerulonephritis. Kidney biopsy showed intense staining for IgA, IgA1 and C3 in a linear pattern along the glomerular basement membrane (GBM). Serologic tests for detecting anti-GBM antibodies were positive for IgA class and IgA1 subclass and negative for IgG and IgA2. Serum IgA anti-GBM antibodies appeared essentially in the polymeric form, an observation in agreement with recent studies demonstrating polymeric IgA response after parenteral immunization. There was no sign of pulmonary involvement. This patient is the first to present with an isolated nephritis due to anti-GBM antibodies restricted to the IgA class (IgA1 subclass). Routine tests for circulating anti-GBM antibodies should also include the IgA class.     

De-novo anti-GBM-antibody-induced glomerulonephritis in a renal transplant

We report a case of de-novo anti-glomerular basement membrane antibody induced glomerulonephritis (anti-GBM GN) in a renal cadaveric transplant. The 52 year old male patient had developed end-stage renal failure secondary to malignant hypertension. His initial renal transplant lost function within two months because of severe allograft rejection without evidence of anti-glomerular basement membrane (anti-GBM) antibody formation. Eight months after his second cadaveric transplant he developed the nephrotic syndrome. This was followed by a rapid deterioration in graft function associated with the development of diffuse proliferative glomerulonephritis with 100% crescent formation. Linear staining of the GBM with IgG and C3 and the presence of circulating anti-GBM antibodies confirmed the anti-GBM antibody etiology of the glomerular lesion. Thus anti-GBM antibody induced glomerulonephritis can occur de-novo in a transplanted kidney despite routine immunosuppression. This represents either coincidental autoantibody production after transplantation or specific alloantibody production, stimulated by the introduction, by transplantation, of GBM neoantigens.     

Case of scleroderma with rapid progressive glomerulonephritis associated with both MPO-ANCA and anti-GBM antibodies

A 66-year-old male with scleroderma developed rapidly progressive glomerulonephritis (RPGN). Renal pathology revealed crescentic glomerulonephritis with interstitial inflammation and fibrosis. Immunofluorescent micrography showed linear deposition of IgG along the glomerular capillary wall. Both anti-glomerular basement membrane antibody (anti-GBM Ab), and myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) were detected by an enzyme-linked immunosorbent assay (ELISA). These findings were compatible with ANCA-related vasculitis and anti-GBM Ab nephritis. Laboratory findings showed rapid elevation of the serum creatinine level (5.9 mg/dL), and a high titer of MPO-ANCA (530 EU) and anti-GBM Ab (21 EU). He was started on methylprednisolone pulse therapy and temporary hemodialysis. Since the immunosuppressive therapy lowered both antibody titers steadily and improved renal function, hemodialysis was discontinued 4 weeks after the therapy. It has been reported that some scleroderma patients developed rapid progressive glomerulonephritis due to ANCA-associated vasculitis in addition to the typical scleroderma renal crisis. There have been few reports of a scleroderma patient associated with RPGN, in whom both MPO-ANCA and anti GBM antibodies were detected.     

Superimposed glomerular immune complexes in anti-glomerular basement membrane disease

The association of anti-glomerular basement membrane (GBM) antibody-mediated glomerulonephritis and glomerular immune complexes is common and probably arises from a number of mechanisms. In the series, glomerular immune complexes were identified in 6 of 17 patients who initially presented with anti-GBM disease. In four cases, glomerular immune complexes were noted in renal biopsies obtained at clinical presentation; in the other two, they were first demonstrated seven and 28 months after presentation, when circulating anti-GBM antibody levels were undetectable. Circulating immune complexes were detected in only two of six patients, either 28 months before or 17 months after the demonstration of the glomerular membranous lesion. The association of glomerular immune complexes and anti-GBM disease may be coincidental with immunologically-unrelated immune complexes localizing in the GBM for physico-chemical reasons; or the presence of glomerular-bound anti-GBM antibodies may predispose to the deposition of molecules with particular affinity for these antibodies. One patient with glomerular immune complexes used heroin, which may be associated with immune complex formation and the development of glomerulonephritis; and one patient was subsequently thought to have systemic lupus erythematosus (SLE). An antecedent infection was found in two of the four patients who had glomerular complexes at presentation, but in only three of 13 with uncomplicated anti-GBM disease. Three of 6 patients with superimposed glomerular complexes had a history of exposure to organic solvents before the onset of disease, while none in the group with anti-GBM disease alone had.     

IgA antiglomerular basement membrane disease associated with bronchial carcinoma and monoclonal gammopathy

Antiglomerular basement membrane (anti-GBM) disease is characterized by a linear deposition of immunoglobulins along the glomerular basement membrane. A 67-year-old man with a recently discovered monoclonal gammopathy of unknown significance (MGUS) presented with microscopic hematuria, nephrotic-range proteinuria, and rapidly deteriorating renal function after a pneumonia. Renal histology showed a crescentic glomerulonephritis; immunohistology showed intense linear staining of the GBM with immunoglobulin A (IgA) and moderate linear staining with kappa and lambda light chains. Screening for systemic disease, including diabetes mellitus, lupus erythematodes disseminatus, cryoglobulinemia, was negative. Serological tests for detection of anti-GBM antibodies were positive for IgA class and negative for IgG. Further examination indicated a bronchial carcinoma T2N2M0. This clinical report adds new information to the spectrum of anti-GBM disease and suggests that neoplasia may be associated with unusual exposure of and/or immune response to epitopes in the GBM.     

Une artérite à cellules géantes révélatrice d’un syndrome de Goodpasture

Goodpasture's syndrome is a triad of anti-glomerular basement membrane (anti-GBM) circulating antibodies, glomerulonephritis and pulmonary hemorrhage. We reported a 65-year-old woman with headaches, asthenia and weight loss. Giant cell arteritis was confirmed by temporal artery biopsy. The patient had associated renal condition with moderate acute renal failure, proteinuria and haematuria. Renal biopsy showed extracapillary glomerulonephritis and linear staining of immunoglobulins G along glomerular basement membrane. There was no clinical pulmonary involvement. Anti-MBG antibody was positive and allowed Goodpasture's syndrome diagnosis. The patient was treated with corticoids and cyclophosphamide. Patient's condition and renal function improved quickly and anti-MBG antibodies became negative. Goodpasture's syndrome may be characterized by isolated renal expression without pulmonary involvement. We described for the first time association of Goodpasture's syndrome with giant cell arteritis.     

Transformation of membranous glomerulonephritis into crescentic glomerulonephritis with glomerular basement membrane antibodies. Serial determinations of anti-GBM before the transformation

This case report describes a patient who initially had a pleuritis and arthalgias. During the follow-up he developed first a membranous glomerulonephritis with nephrotic syndrome and subsequently a crescentic, rapidly progressive glomerulonephritis with glomerular basement membrane antibodies (anti-GBM). An analysis of the serum samples obtained during the follow-up revealed no infections at the onset of renal failure. However, anti-GBM could be demonstrated in the serum samples obtained 2 months before the deterioration of the renal function. The anti-GBM did not react with alveolar BM and the patient had no signs of pulmonary hemorrhage. The etiology and the sequence of the pathological events of rapidly progressive glomerulonephritis is discussed in the light of these observations.     

Failure of heparin to affect two types of experimental glomerulonephritis in rabbits.

Anticoagulation has been reported to ameliorate antiglomerular basement membrane glomerulonephritis (anti-GBM-GN) while its effect on chronic immune complex glomerulonephritis (IC-GN) as studied in the NZB mouse is unclear. Chronic serum sickness IC-GN was induced in rabbits by injecting bovine serum albumin (BSA) daily. Anti-GBM-GN was induced by i.v. injection of a known amount of heterologous anti-GBM antibody. Heparin was administered beginning at two to six weeks after the first BSA injections or before the administration of anti-GBM antibody, on various schedules from 5000 U every 12 hr to 8000 U every 8 hr. With this dosage the partial thromboplastin time remained greater than 1-1/2 to 2-1/2 times the control at the time of the subsequent heparin injection. Heparinized and nonheparinized groups were matched according to duration of disease, maximum anti-BSA concentrations or anti-GBM antibody dosage--and no significant differences were found in proteinuria; severity of the glomerular histologic lesions; or immunofluorescence patterns of immunoglobulin G (IgG), third component of complement (C3), BSA or fibrinogen-related antigen(s) (FRA). Crescent formation was not prevented. This study shows that heparin in the maximum permissible dosage is ineffective in preventing glomerular FRA deposition or altering the progression of experimental IC-GN or anti-GBM-GN in rabbits.     

Progressive glomerular sclerosis in experimental antiglomerular basement membrane glomerulonephritis

A model of chronic progressive glomerular sclerosis in experimental antiglomerular basement membrane (anti-GBM) glomerulonephritis was developed in Wistar rats. Wistar rats given the accelerated form of anti-GBM anti-body glomerulonephritis initially developed significant proteinuria and renal insufficiency associated primarily with a decrease in glomerular filtration rate (GFR) with normal renal clearance of para-aminohippuric acid and with markedly reduced filtration fraction. The glomerular functional abnormalities were associated with marked glomerular hypercellularity due to leukocytic infiltration as well as proliferation of intrinsic glomerular cells with crescent formation. Late in the course of the disease, by day 21, GFR had fallen further, associated with a parallel decrease in the clearance of para-aminohippuric acid and a normal filtration fraction. At this stage, glomerular hypercellularity had diminished and was replaced by glomerular sclerosis. The model appears to be a reproducible form of chronic glomerulosclerosis and demonstrates that the chronic phase of glomerular basement membrane (GBM) glomerulonephritis is distinctly different from that of the acute phase. It provides a controllable setting to study the glomerular sclerotic process independent of the initial inflammatory changes.     

Renal entactin (nidogen): isolation, characterization and tissue distribution.

Entactin/nidogen (E/N) was isolated from bovine renal tubular basement membrane. Apparent molecular weight, amino acid composition, and molecular configuration by electron microscopy rotary shadowing were similar to that of nidogen from EHS mouse tumor. The identity of bovine E/N was confirmed using a thrombin derived peptide, the sequence of which corresponded to a region within mouse and human E/N. Monoclonal and polyclonal anti-E/N antibodies were used to determine the distribution of E/N in human kidney by immunofluorescent and immunoelectron microscopy. E/N was present in all renal basement membranes and was distributed through the full width of the glomerular basement membrane (GBM) with accentuation along its epithelial aspects. E/N distribution was similar to that of novel collagen chain alpha 3(IV) NC domain in the GBM. In the mesangium, E/N was distributed mainly in the peripheral mesangial region that is bounded by the GBM, while classical collagen chain alpha 1(IV) NC as present diffusely throughout the mesangium. In the developing nephron, E/N was present in basement membranes of the ureteric bud, primitive vesicle and S-form. In all instances, E/N co-localized with laminin B2 chain. Prominent E/N detection within the mesangium was observed in diseases where mesangial expansion was present. This process was also seen in early diabetic nephropathy, but disappeared with disease progression. However, all thickened diabetic renal basement membranes showed an increase in E/N which was also present in Kimmelstiel-Wilson lesions. E/N was observed in the GBM "spikes" of membranous glomerulonephritis and in epithelial crescents associated with various disorders. The association between E/N, laminin and type IV collagen chains observed in the normal kidney were maintained in disorders with altered E/N distribution. We could not detect any changes in the distribution of E/N in other acquired and hereditary kidney diseases. These observations reflect the involvement of E/N in the structure and disease alteration of renal basement membranes and mesangial matrix.     

Heterogeneity of antigen expression explains controversy over glomerular macrophage accumulation in mouse glomerulonephritis.

BACKGROUND: Many antibody labelling studies have suggested that there are few or no glomerular macrophages in mouse models of glomerulonephritis, despite the presence of a prominent interstitial macrophage infiltrate. These findings conflict with studies of human and rat glomerulonephritis. Therefore, we examined whether heterogeneity of macrophage antigen expression could explain this apparent discrepancy. METHODS: Kidneys were collected from normal mice and mice killed at 2 and 10 days after induction of accelerated anti-glomerular basement membrane (GBM) glomerulonephritis. Following fixation, macrophages were detected by immunoperoxidase staining in serial kidney sections using antibodies recognising CD11b, F4/80 and CD68. RESULTS: Induction of anti-GBM nephritis caused a progressive increase in glomerular and interstitial leukocytes. At days 2 and 10, there were more CD68+ macrophages in glomeruli than macrophages expressing CD11b or F4/80. At day 10, CD68+ macrophages accounted for almost all glomerular CD45+ total leukocytes. In contrast, CD11b+ and F4/80+ macrophages at day 10 accounted for only 65 and 13% of glomerular leukocytes, respectively. However, in the interstitium the number of macrophages expressing CD68, CD11b and F4/80 were not different. CONCLUSION: Antibody detection of mouse CD68 identifies all glomerular macrophages in mouse anti-GBM nephritis, indicating a similar infiltrate to that seen in human and rat anti-GBM nephritis. Our finding of substantial heterogeneity in glomerular macrophage antigen expression in this model suggests that previous studies of mouse glomerulonephritis may have underestimated glomerular macrophages and their role in glomerular injury.     

Experimental autoimmune glomerulonephritis induced by homologous and isologous glomerular basement membrane in Brown-Norway rats

In order to study disease mechanisms and potential forms of therapy in glomerulonephritis, a model of experimental autoimmune glomerulonephritis (EAG) has been developed in the rat. We have examined the response of Brown-Norway (BN) rats to a single i.m. injection of collagenase-solubilised homologous (Sprague-Dawley, SD) or isologous (BN) glomerular basement membrane (GBM), with and without complete Freund's adjuvant (CFA). There was a dose-dependent circulating anti-GBM antibody response to all preparations of rat GBM. Animals given either antigen alone at a dose of 2 mg/kg developed circulating anti-GBM antibodies, which reached peak values by 6 weeks (63 +/- 5% following SD GBM; 53 +/- 8% following BN GBM), but did not develop glomerular deposits of IgG or nephritis. Animals given 2 mg/kg SD GBM in CFA developed greater concentrations of anti-GBM antibody by 6 weeks (122 +/- 20%) together with linear deposits of IgG on glomerular and tubular basement membranes (TBM), albuminuria (mean 7 mg/24 h), and variable focal segmental necrotising glomerulonephritis with mild interstitial nephritis. The same dose of BN GBM in CFA produced similar concentrations of circulating antibody (144 +/- 26%), with linear deposits of IgG on GBM but rarely TBM, little albuminuria, and variable mild focal glomerulonephritis. Other strains injected with SD GBM in CFA showed a variable circulating anti-GBM antibody response, which was similar to that of BN rats in PVG and DA rats but lower in LEW and WAG rats. Linear deposits of IgG on the GBM were detected in a proportion of PVG and DA rats, but not in LEW or WAG rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

A 25-year experience with pediatric anti-glomerular basement membrane disease

Anti-glomerular basement membrane (anti-GBM) disease, which is extremely uncommon in children, is characterized by rapidly progressive glomerulonephritis (RPGN) and autoantibodies against GBM collagen. Pulmonary hemorrhage is the third component in Goodpasture Syndrome. Cigarette smoking and exposure to hydrocarbons have been linked to anti-GBM disease in adults, but such an association has not been established in children. We reviewed renal biopsy and autopsy specimens over 25 years from a major tertiary care U.S. children's hospital, diagnosing anti-GBM by clinical RPGN, crescentic glomerulonephritis, and linear immunofluorescence (IF) immunoglobulin G staining in patients under 18 years of age. We identified four patients, with and without pulmonary manifestations. The sole autopsy case showed diagnostic IF despite undetectable serum anti-GBM antibodies and positive testing for serum anti-neutrophil cytoplasmic antibodies (ANCA). Three patients have survived 1–18 years following diagnosis, one of whom is recovering renal function. One adolescent had a history of smoking cigarettes and one had a probable hydrocarbon exposure. Anti-GBM disease is unusual in children, and the relationship to inhaled agents is incompletely understood. Serum anti-GBM antibodies are typically present, but cases with undetectable levels can occur. Some patients are anti-GBM and ANCA positive, with a small subset ANCA-positive, anti-GBM-negative. Ours is the first such described pediatric case.     

Fibrillary glomerulonephritis presenting as rapidly progressive glomerulonephritis

Fibrillary glomerulonephritis (GN) is an uncommon cause of rapidly progressive kidney failure. We report a case of rapidly progressive kidney failure with kidney biopsy showing crescentic GN on light microscopy and immunofluorescence showing linear/globular glomerular basement membrane (GBM) staining for immunoglobulin G and C3, consistent with anti-GBM disease. However, electron microscopy showed fibrillary deposits in the GBM, suggesting a diagnosis of fibrillary GN. As exemplified by this case, it is important to consider fibrillary GN in the differential diagnosis of crescentic GN with linear immunoglobulin G deposits within the GBM. Electron microscopy is crucial to make this diagnosis.     

Experimental autoimmune Goodpasture's disease: a pathogenetic role for both effector cells and antibody in injury

BACKGROUND: Goodpasture's disease [antiglomerular basement membrane (GBM) glomerulonephritis] is a classic autoimmune disease and the only organ-specific autoimmune renal disease in which the antigen is well described. The importance of antibodies against the non-collagenous domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1] is well established. However, observational human studies and studies in experimental systems also imply a role for cell-mediated effector injury. METHODS: Active experimental autoimmune glomerulonephritis (EAG) was induced by immunization with alpha3-alpha5(IV)NC1 heterodimers in B cell intact C57BL/6 mice and B cell (mu chain-deficient) mice. Passive disease was induced by transferring sera from B cell intact and B cell deficient mice with EAG to RAG-1-/- mice (that lack adaptive immunity). Histologic and functional injury was studied. RESULTS: Despite the absence of B cells and immunoglobulin in B-cell-deficient mice, histologic and functional injury developed in mice immunized with alpha3-alpha5(IV)NC1, with T cells and macrophages in glomeruli. Injury occurred to a similar degree to that found in B-cell-intact mice. Transfer of sera from B-cell-intact mice with EAG containing antibodies (but not from B-cell-deficient mice with EAG) to RAG-1-/- mice induced linear immunoglobulin deposits on the glomerular basement membrane (GBM) and pathologic proteinuria. CONCLUSION: Both cell-mediated and humoral effectors are capable of inducing renal injury in EAG. Given the similarity of the disease-initiating antigen in this model to the antigen in human anti-GBM glomerulonephritis, similar overlapping mechanisms are likely to operate in human disease.     

Evidence of both anti-GBM and immune complex mediated pathogenesis in the initial phase of Goodpasture's syndrome.

A 19 year old women presented with pulmonary hemorrhage, rapidly progressive glomerulonephritis and antiglomerular basement membrane antibody in her serum. In the initial phase of the disease a double layered linear deposit of IgG was seen on the glomerular capillary basement membrane together with a finely granular or focal and lumpy single layer deposit of C3 and numerous small subepithelial electron dense deposits. These findings are suggestive of the simultaneous occurrence of anti-GBM and immune complex glomerulonephritis.     

Diabetic nephropathy with interstitial nephritis presenting with a false-positive anti-GBM antibody

A 56-year-old male with DM and HTN presented with flank pain and nausea. Review of systems was negative, physical examination was notable for mild hypovolemia and laboratory revealed BUN 51 mg/dl, creatinine (Cr) 5.1 mg/dl (baseline 1.5), Westergren ESR 122 mm/h, fractional excretion of sodium 0.2% and UA positive for blood and protein. Despite volume resuscitation the Cr continued to rise. Urine sediment analysis revealed granular casts, renal tubular epithelial cells and a negative Hansel's stain. Hemodialysis was initiated with Cr 13.7 mg/ dl for dyspnea and dysgeusia. Subsequent laboratory data revealed 2 separate positive anti-GBM antibody titers and prednisone therapy was initiated. Renal biopsy was performed for further diagnostic, therapeutic and prognostic information and demonstrated interstitial nephritis with linear IgG and albumin deposition consistent with diabetic nephropathy. Follow-up antibody titers were negative. prednisone was discontinued and Cr stabilized with conservative therapy. Anti-GBM antibody disease is characterized by circulating IgG antibodies directed against the glomerular basement membrane, specifically the alpha-3 (IV) collagen chain. Anti-GBM nephritis is a rapidly progressive, isolated glomerulonephritis in association with circulating anti-GBM antibodies. A positive immunofluorescence (IF) test is considered diagnostic in the appropriate clinical setting. Therapies include immunosuppressive agents to suppress new antibody production and plasmapheresis to eliminate circulating antibodies. Anti-GBM antibody is not rapidly cleared by steroid therapy and the recovery of renal function is rare if initiation Cr is greater than 7 mg/dl. This case demonstrates that the current ELISA for alpha-3 (IV) collagen is not pathognomonic for anti-GBM nephritis and that renal biopsy with IF for IgG and albumin may be indicated to prevent administration of potentially toxic treatment.