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MPO-ANCA associated crescentic glomerulonephritis with numerous immune complexes: case report
© Morizane et al.; licensee BioMed Central Ltd. 2012
Received: 30 November 2011
Accepted: 17 May 2012
Published: 1 June 2012
Antineutrophil cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis (CGN) is a major cause of rapidly progressive glomerulonephritis (RPGN). ANCA-associated CGN is generally classified into pauci-immune RPGN, in which there are few or no immune complexes.
A 78-year-old man presented with RPGN after a 7-year course of chronic proteinuria and hematuria with stable renal function. A blood examination showed a high titer of myeloperoxidase (MPO)-ANCA. A renal biopsy showed crescentic glomerulonephritis with abundant subepithelial, intramenbranous and subendothelial deposits by electron microscopy, leading to the diagnosis of ANCA-associated CGN superimposed on type 3 membranoproliferative glomerulonephritis (MPGN).
This case is unique in that type 3 MPGN and MPO-ANCA-associated CGN coexisted, and no similar case has been reported to date. Because ANCA-associated CGN has a predilection for elderly individuals and primary type 3 MPGN is rarely seen in this age group, coincidental existence appears less likely. This case may confer valuable information regarding the link between immune complex and ANCA-associated CGN.
In elderly people, myeloperoxidase (MPO) and proteinase-3 (PR3) antineutrophil cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis (CGN) is a major cause of rapidly progressive glomerulonephritis (RPGN). ANCA-associated CGN is generally classified into pauci-immune RPGN, in which there are few or no immune complexes. We have experienced a rare case of ANCA-associated CGN with extensive glomerular immune deposits supposed as type 3 membranoproliferative glomerulonephritis (MPGN). Since idiopathic MPGN is rarely seen in elderly subjects, coincidence of ANCA-associated CGN and MPGN appears less likely. Here, we present a case showing quite unique pathological findings and further discuss the possible association between ANCA-associated CGN and immune complex disease.
A 78-year-old Japanese man was admitted to our hospital because of rapidly declining renal function. The patient had been treated for hypertension since the age of 63 years at our hospital and was initially free of proteinuria with normal renal function. Despite satisfactory control of hypertension, he began to exhibit proteinuria with microscopic hematuria at the age of 71 years. Proteinuria gradually increased to 2 grams per day over the ensuing six months. Laboratory and imaging studies for connective tissue disease, malignancy, dysproteinemia, and hepatitis viral infection were uninformative, but a test for antinuclear antibodies was weakly positive and a high-resolution computed tomography scan showed mild interstitial pneumonia. Although a renal biopsy was recommended at this time, the patient did not consent to the procedure, but received antihypertensive treatment under the close observation. Proteinuria and microscopic hematuria persisted, and his serum creatinine remained at the level of 1.2 to 1.4 mg/dL. Seven years after the onset of the proteinuria, however, the patient’s serum creatinine level rose rapidly from 1.4 mg/dL to 8.1 mg/dL over a period of 2 months, and he was admitted to our hospital.
The patient was 167.5 cm tall and weighed 64.7 kg. His blood pressure was 142/77 mmHg. His body temperature was 35.8°C. The palpebral conjunctivae showed pallor, and marked edema was present in the lower extremities. No respiratory or neurologic abnormalities were apparent.
Laboratory data on admission
white blood cell count
536 EU (normal, < 20 EU)
plate let count
hepatitis B antigen
hepatitis c antigen
337 U/ml (normal, <500 U/mL
aspartate amino transferase
surfactant protein D
77 ng/mL (normal, 110 ng/mL)
alanine amino transferase
surfactant protein A
56.5 ng/mL (normal, <43.8 U/mL
71 mg/dL (normal, 60-116 mg/dL)
42 mg/dL (normal, 15-44 mg/dL)
49.4 U/mL (normal, 25.0-48.0 mg/dL)
The patient was treated with high-dose prednisolone for 6 weeks following 3 days of intravenous pulse methylprednisolone treatment. Cyclophosphamide was not administered when his age and the risk of infection were deliberately taken into consideration. Although the MPO-ANCA titer decreased with steroid therapy, the patient’s renal function failed to improve and prednisolone was tapered. The patient was subsequently discharged from the hospital and continued to receive maintenance hemodialysis therapy on an outpatient basis.
Our patient presented with a clinical picture of RPGN, with a high serum titer of MPO-ANCA preceded by seven years of proteinuria and microscopic hematuria with mildly compromised but stable renal function. Renal biopsy showed diffuse glomerular crescent formation as well as abundant deposits and diffusely thickened capillary walls by light microscopy. Because the co-existence of membranous nephropathy and ANCA-associated CGN was shown in previous reports [1–5], we inferred a priori that MPO-ANCA-associated CGN was superimposed on membranous nephropathy. Electron microscopic observation, however, revealed not only subepithelial but also numerous intramembranous and subendothelial deposits, which are rarely observed in membranous nephropathy. These findings rather favor a diagnosis of MPO-ANCA-associated CGN superimposed on type 3 MPGN, although mesangial proliferation was only modest. Type 3 MPGN, however, is rarely seen in elderly people, and no reports have previously been made showing ANCA-associated CGN superimposed on type 3 MPGN.
It has been widely accepted that the paucity of immunoglobulin deposits distinguishes ANCA-associated CGN from immune complex glomerulonephritis and anti-GBM glomerulonephritis, leading to the belief that immune complexes do not play a role in ANCA-associated CGN. Nevertheless, several studies suggest that glomerular immune complex deposition and ANCA-positivity are not necessarily mutually exclusive. Falk et al.  demonstrated that a considerable number of patients with immune complex glomerulonephritis were positive for ANCA. Furthermore, ANCA is reported to be detected in various immune complex-mediated nephropathy, including IgA nephropathy [7, 8], post-infectious glomerulonephritis , membranous nephropathy , lupus nephritis [10–12], glomerulonephritis of hypocomplementemic urticarial vasculitis syndrome , glomerulonephritis of hepatitis C virus infection [14, 15] and glomerulonephritis of subacute bacterial endocarditis . These observations suggest a possible link between immune complex and ANCA in a subset of glomerulonephritis.
Alternatively, Neumann et al.  evaluated 45 patients with systemic small vessel vasculitis and CGN or idiopathic CGN, and found substantial immunoglobulin deposition in 8 of 45 cases (18%), using the immune-peroxidase method. Haas et al.  also demonstrated the presence of electron-dense deposits in 68 cases (54%) among 126 patients of CGN associated with ANCA and/or necrotizing angiitis. Finally, in a study in which renal biopsy was performed in 74 patients with primary ANCA-associated systemic vasculitis, 23 cases (31%) possess immune complex deposition, as assessed by immunofluorescence and/or electron microscopy . In concert, the presence of glomerular immune complex deposition does not preclude the presence of ANCA or ANCA-associated CGN.
Cases of secondary MPGN with positive ANCA
Type of ANCA
type 1 MPGN with crescent IgG/M/C1q/C3 in subendothelium
c-ANCA 1:1000 ELISA: 39 IU/ml
proteinuria (2.1 g/day)
type 1 MPGN IgM/A/C3 in subepithelial
carbamazepine induced autoimmune
type 1 MPGN with crescent IgG/M/C1q/C3 in subendothelium
Herein, the authors present a case with unique pathological changes showing a possible link between ANCA-associated nephropathy and immune complex. The implication that immune complex-mediated glomerular injury plays a pathogenetic role in a subset of ANCA-associated crescentic glomerulonephritis warrants further investigations.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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