Membranous glomerulonephritis with ANCA-associated necrotizing and crescentic glomerulonephritis

Abstract

Background and objectives: Only rare cases of concurrent membranous glomerulonephritis (MGN) and antineutrophil cytoplasmic antibody (ANCA)-associated necrotizing and crescentic glomerulonephritis (NCGN) have been reported.

Design, setting, participants, & measurements: The authors report the clinical and pathologic findings in 14 patients with MGN and ANCA-associated NCGN.

Results: The cohort consisted of eight men and six women with a mean age of 58.7 yr. ANCA positivity was documented by indirect immunofluorescence or ELISA in all patients. Indirect immunofluorescence was positive in 13 patients (seven P-ANCA, five C-ANCA, one atypical ANCA). ELISA was positive in nine of 10 patients (five MPO-ANCA, three PR3-ANCA, one MPO- and PR3-ANCA). Clinical presentation included heavy proteinuria (mean 24-hr urine protein 6.5 g/d), hematuria, and acute renal failure (mean creatinine 4.4 mg/dl). Pathologic evaluation revealed MGN and NCGN, with crescents involving a mean of 32% of glomeruli. On ultrastructural evaluation, the majority of cases showed stage I or II membranous changes. Follow-up was available for 13 patients, 12 of whom were treated with steroids and cyclophosphamide. At a mean follow-up of 24.3 mo, five patients progressed to ESRD, seven had stabilization or improvement in renal function, and one had worsening renal function. Five patients, including three with ESRD, died during the follow-up period. The only independent predictor of progression to ESRD was serum creatinine at biopsy.

Conclusions: MGN with ANCA-associated NCGN is a rare dual glomerulopathy seen in patients with heavy proteinuria, acute renal failure, and active urine sediment. Prognosis is variable, with 50% of patients reaching endpoints of ESRD or death.

Figure 1.

Renal biopsy findings in patients with membranous glomerulonephritis (MGN) and antineutrophil cytoplasmic antibody-associated NCGN. (A) A glomerulus exhibits segmental fibrinoid necrosis, GBM rupture, and an early segmental cellular crescent. There is no evidence of glomerular basement membrane (GBM) spike formation in this patient with stage 1 MGN. (Jones methenamine silver). (B) Another glomerulus displays more extensive fibrinoid necrosis, multifocal GBM rupture, and a large cellular crescent. (Jones methenamine silver). (C) Immunofluorescence staining for IgG reveals granular global glomerular capillary wall positivity, typical of MGN. (D) Immunofluorescence staining for IgG reveals mild intensity, segmental capillary wall positivity in this patient with segmental MGN. (Magnification, ×400 in A-D). (E) Ultrastructural evaluation reveals global subepithelial electron dense deposits, the majority of which lie adjacent to GBM spikes. The findings appear most consistent with stage 2 MGN. (Magnification, ×4,000).