A case of anti-glomerular basement membrane glomerulonephritis superimposed on membranous nephropathy
Takashi Sano1,
Kouju Kamata1,
Hidekazu Shigematsu2 and
Yutaka Kobayashi1,
1 Department of Medicine, School of Medicine, Kitasato University, Sagamihara City, and
2 School of Medicine, Shinshu University, Matsumoto City, Japan
Keywords: anti-glomerular basement membrane glomerulonephritis; crescentic glomerulonephritis; membranous nephropathy
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Introduction
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There are two major mechanisms of immunological injury to the glomerulus. The first type is characterized by glomerular deposition of immune complexes, which occurs in the nephropathy of systemic lupus erythematosus, membranous nephropathy, etc. In the second variety, injury is mediated by anti-glomerular basement membrane (anti-GBM) antibody. Anti-GBM antibody mediated injury is most frequently characterized by crescentic glomerulonephritis and rapid deterioration of renal function with or without pulmonary haemorrhage. Simultaneous occurrence of membranous nephropathy and anti-GBM glomerulonephritis has been rarely reported. We report the clinical and histological features of a patient with anti-GBM glomerulonephritis superimposed on membranous nephropathy.
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Case
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A 54-year-old woman was admitted to Kitasato University Hospital in June 1993 because of gross haematuria, proteinuria, and rapid renal function deterioration. Microscopic haematuria, proteinuria, and normal renal function (serum creatinine 0.7 mg/dl) had been detected in July 1992. Eight days prior to admission, the patient experienced nausea, headache, dark urine, oliguria, and swelling of the lower extremities. She had no history of haemoptysis, arthralgia, or skin rashes. On admission, slight bilateral pretibial oedema was noted and her blood pressure was 140/72 mmHg, pulse 76/min with a regular rhythm, and temperature 37.5°C. Urinalysis showed 3+ for protein with numerous red blood cells in the sediment. Haematocrit was 28.2%; white blood cell count was 9600/mm3 with 88% neutrophils, 10% lymphocytes, 1% monocytes, 0% eosinophils, and 1% basophils; platelet count was 273 000/mm3 and erythrocyte sedimentation rate was 118 mm/h. Blood urea nitrogen was 48 mg/dl, serum creatinine 8.9 mg/dl, total serum protein 4.9 g/dl (albumin 2.3 g/dl,
1-globulin 0.4 g/dl,
1-globulin 1 g/dl, ß-globulin 0. 6 g/dl,
-globulin 0.6 g/dl), and cholesterol 154 mg/dl. C-reactive protein was 22 055 µg/dl, and the titres of antistreptolysin-O, antistreptokinase, and serum complement were within normal range. LE test, a test for antinuclear antibody, anti-DNA antibody and HB antigen were negative. Circulating immune complex was 0.5 µg/ml and P- and C-ANCAs were negative. Circulating anti- GBM antibody was 1346 units (negative range, less than 9 units). Indirect immunofluorescence of the patient's serum revealed apparent linear localization along the glomerular capillary walls of normal kidney (Figure 1A
). A chest X-ray showed cardiomegaly and lung congestion. An electrocardiogram was normal. Renal ultrasound showed normal kidneys.

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Fig. 1. (A) A portion of a glomerulus from a normal kidney demonstrating linear deposition of patient IgG (indirect method of patient serum and FITC-labelled goat antihuman IgG antibody) (x750). (B) A portion of a glomerulus from a patient renal biopsy specimen exhibiting finely granular and linear ( ) deposition of IgG along the capillary walls (x700).
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On her first hospital day, haemodialysis was initiated because of uraemia. Percutaneous renal biopsy was performed on the second day. Light microscopy revealed crescentic glomerulonephritis. The number of glomeruli in the biopsy specimen was 25. All glomeruli showed circumferential cellular crescent formation consisting of monocyte-epithelial cells (Figure 2A
). In the glomerular capillary lumina, many polymorphonuclear leukocytes and mononuclear cells were observed, often accompanying fibrin deposits. Fibrin deposits were also seen to be extravasated into urinary spaces. Surviving glomerular capillary walls were seen to be compressed. On PAM staining, glomerular capillary walls exhibited spike lesions and a bubbling appearance. Diffuse interstitial cell infiltration was observed in accordance with tubular degeneration and tubulitis. No prominent vascular changes were observed. Immunofluorescence demonstrated coexistent finely granular and linear depositions of IgG and C3 along the glomerular capillary walls (Figure 1B
). Electron microscopy showed subepithelial electron dense deposits (Figure 2B
). Based on these histological findings, a diagnosis of anti-GBM glomerulonephritis superimposed on membranous nephropathy was reached.

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Fig. 2. (A) A glomerulus showing a circumferential cellular crescent compressing the capillary tufts (x350, PAM). (B) Subepithelial electron-dense deposits are observed along the glomerular basement membrane. Subendothelial spaces are widened ( ). Monocytes (Mo) are observed in the capillary lumina, showing direct contact with the glomerular basement membrane (x2500).
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The patient was treated with plasmapheresis four times and pulse intravenous methylprednisolone of 1 g for 3 days during the early phase of the disease, followed by an oral prednisolone regimen (60 mg/day). In spite of the aggressive treatment, renal function never improved. The immunosuppressive treatment was then discontinued and the patient went into maintenance haemodialysis therapy.
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Discussion
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We encountered a case of anti-GBM glomerulonephritis with membranous nephropathy. Clinically, this patient presented rapidly progressive renal dysfunction in clinical aspects. Histologically, light microscopy showed circumferential crescent formation in all glomeruli. Intense immunofluorescent staining for IgG and C3 was observed along glomerular capillary walls. The staining showed simultaneous fine granular and linear patterns. Electron microscopy revealed diffuse subepithelial dense deposits. These findings suggested the superimposition of anti-GBM glomerulonephritis on membranous nephropathy.
To our knowledge, since Klassen et al. [1] initially reported a patient with membranous nephropathy who developed rapidly progressive glomerulonephritis associated with anti-GBM antibodies in 1974, 12 cases with the same condition have been reported [111], including four cases of Goodpasture's syndrome. Table 1
lists all cases of membranous nephropathy with anti-GBM glomerulonephritis including ours. Most patients were treated by corticosteroids, immunosuppressive drugs, and plasmapheresis. However, favourable outcomes were only achieved for three cases. Herody et al. [12] reported that creatininaemia over 600 µmol/l, oligoanuria, absence of normal glomeruli, a high percentage of circumferential crescents, and a high level of circulating anti-GBM antibodies evaluated by ELISA are features that indicate an unfavourable renal course. In fact, our patient went into irreversible renal failure requiring chronic haemodialysis, although corticosteroid treatment including pulse methylprednisolone therapy and plasmapheresis were performed.
Rapid decline in renal function may occur in membranous nephropathy patients with additional superimposed factors such as severe hypertension, renal vein thrombosis, crescentic glomerulonephritis [13,14], and anti-GBM mediated disease [111]. Human anti-GBM mediated disease is an autoimmune disorder characterized by autoantibodies directed against the non-collagenous NC1 domain of the
3(IV) chain of type IV collagen [15]. Klassen et al. [1] speculated that deposits in membranous nephropathy might alter the GBM and cause release of normal or altered endogenous GBM into the circulation, resulting in the formation of anti-GBM antibodies. Kurki also suggested that the formation of anti-GBM antibody was due to the alteration and/or the release of hidden GBM antigens [8]. However, the precise mechanism of this transformation of membranous nephropathy into anti-GBM glomerulonephritis is still obscure.
In summary, we describe a patient with anti-GBM glomerulonephritis superimposed on membranous nephropathy. Our patient's renal function rapidly deteriorated, requiring chronic haemodialysis. Considering the results of the reported cases, early diagnosis and aggressive treatment will be required to improve the renal dysfunction.
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Notes
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Correspondence and offprint requests to: Dr Yutaka Kobayashi, Department of Medicine, School of Medicine, Kitasato University, 1151, Kitasato, Sagamihara City, Kanagawa, 2288555 Japan. 
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References
|
---|
-
Klassen J, Elwood C, Grossberg AL et al. Evolution of membranous nephropathy into anti-glomerular-basement-membrane glomerulonephritis. N Engl J Med1974; 290: 13401344[ISI][Medline]
-
Moorthy AV, Zimmerman SW, Burkholder PM, Harrington AR. Association of crescentic glomerulonephritis with membranous glomerulonephropathy: a report of three cases. Clin Nephrol1976; 6: 319325[Medline]
-
Agodoa LCY, Striker GE, George CRP, Glassock R, Quadracci LJ. The appearance of nonlinear deposits of immunoglobulins in Goodpasture's syndrome. Am J Med1976; 61: 407413[ISI][Medline]
-
Pasternack A, Tornroth T, Linder E. Evidence of both anti-GBM and immune complex mediated pathogenesis in the initial phase of Goodpasture's syndrome. Clin Nephrol1978; 9: 7785[ISI][Medline]
-
Sharon Z, Rohde RD, Lewis EJ. Report of a case of Goodpasture's syndrome with unusual immunohistology and antibody reactivity. Clin Immunol Immunopathol1981; 18: 402414[ISI][Medline]
-
Richman AV, Rifkin SI, McAllister CJ. Rapidly progressive glomerulonephritis combined antiglomerular basement membrane antibody and immune complex pathogenesis. Hum Pathol1981; 12: 597604[ISI][Medline]
-
Pettersson E, Tornroth T, Miettinen A. Simultaneous anti-glomerular basement membrane and membranous glomerulonephritis: case report and literature review. Clin Immunol Immunopathol1984; 31: 171180[ISI][Medline]
-
Kurki P, Helve T, von Bonsdorff M et al. Transformation of membranous glomerulonephritis into crescentic glomerulonephritis with glomerular basement membrane antibodies. Nephron1984; 38: 134137[ISI][Medline]
-
Hayano K, Miura H, Fukui H, Otsuka Y, Hattori S. A case of anti-GBM nephritis (crescentic glomerulonephritis) associated with membranous nephropathy. Jpn J Nephrol1992; 7: 821826 (in Japanese)
-
Thitiarchakul S, Lal SM, Luger A, Ross G. Goodpasture's syndrome superimposed on membranous nephropathy. A case report. Int J Artif Organs1995; 18: 763765[ISI][Medline]
-
Meisels IS, Stillman IE, Kuhlik AB. Anti-glomerular basement membrane disease and dual positivity for antineutrophil cytoplasmic antibody in a patient with membranous nephropathy. Am J Kidney Dis1998; 32: 646648[ISI][Medline]
-
Herody M, Bobrie G, Gouarin C, Grunfeld JP, Noel LH. Anti-GBM disease: predictive value of clinical, histological and serological data. Clin Nephrol1993; 40: 249255[ISI][Medline]
-
Tateno S, Sakai T, Kobayashi Y, Shigematsu H. Idiopathic membranous glomerulonephritis with crescents. Acta Pathol Jpn1981; 31: 211219[Medline]
-
Nguyen BP, Reisin E, Rodriguez FH. Idiopathic membranous glomerulopathy complicated by crescentic glomerulonephritis and renal vein thrombosis. Am J Kidney Dis1988; 12: 326328[ISI][Medline]
-
Kalluri R, Wilson CB, Weber M et al. Identification of the
3 chain of type IV collagen as the common autoantigen in antibasement membrane disease and Goodpasture syndrome. J Am Soc Nephrol1995; 6: 11781185[Abstract]
Received for publication: 4.10.99
Revision received 3. 3.00.