A case of anti-GBM glomerulonephritis superimposed on HBV-associated membranous nephropathy

Abstract

In September 2010, a 75-year-old hepatitis B virus (HBV)-positive man was admitted to our hospital because of fever, persistent cough, general fatigue, and leg edema. The patient was a hepatitis B surface antigen carrier with detectable HBV DNA level. On admission, laboratory examination revealed severe inflammatory signs, decreased serum albumin, and renal insufficiency with proteinuria. The patient had rapidly progressive renal insufficiency without pulmonary involvement over the few days after admission. Renal biopsy showed membranous nephropathy (MN) with crescent formation. Further serological study revealed a high titer of anti-glomerular basement membrane (GBM) antibody, suggestive of anti-GBM glomerulonephritis superimposed on HBV-associated MN. For both preventing HBV reactivation during immunosuppressive therapy and treating HBV-associated MN, the administration of entecavir was immediately initiated, and then treatment with plasma exchange (PE) and intravenous methylprednisolone administration was performed. Both HBV DNA level and an anti-GBM titer became undetectable, and clinical remission of MN was subsequently achieved. This was a rare case of an elderly patient with anti-GBM glomerulonephritis superimposed on HBV-associated MN, who was successfully treated with PE, corticosteroid, and entecavir combination therapy.

Keywords: Entecavir; Hepatitis B virus; Immunosuppressive therapy; Membranous nephropathy.

Fig. 1

Renal biopsy specimen. a Periodic acid–silver methenamine (PAM) stain [high-power field (HPF)] showing mild diffuse mesangial proliferation, diffuse thickening of glomerular basement membranes (GBMs), occasional capillary wall subepithelial spikes (arrows), and frequent internal vacuolizations (original magnification, ×400; ×1000 insert; PAM stain). b Periodic acid-Schiff (PAS) stain (HPF) showing cellular crescents and segmental necrosis, with compression or destruction of capillary loops and Bowman’s capsule (×400; PAS stain). c PAS stain (low-power field) showing that, around glomeruli with crescent formation, severe tubulointerstitial damage was accompanied by the infiltration of lymphocytes, plasma cells, neutrophils, and eosinophils, but not by vasculitis (×100; PAS stain). d Immunofluorescence staining showing diffuse, fine granular staining on capillary loops with an underlying bright linear staining of the GBMs corresponding to anti-GBM antibody (×800). e Electron microscopy revealed numerous scattered subepithelial and intramembranous deposits, some of which appear electron-lucent (black arrow), and complete overlying foot process effacement. Morphological clues in this case indicating that the membranous nephropathy (MN) is secondary rather than primary include occasional mesangial deposits and mesangial proliferation (white arrow) (×2000)

Fig. 2

Clinical course. mPSL methylprednisolone, PSL prednisolone, UP/Cr spot protein-to-creatinine ratio, Cr serum creatinine, Alb serum albumin, GBM anti-GBM antibody