Membranous glomerulonephritis with ANCA-associated necrotizing and crescentic glomerulonephritis

Clin J Am Soc Nephrol. 2009 Feb;4(2):299-308. doi: 10.2215/CJN.04060808. Epub 2009 Jan 21.

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.

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / immunology
  • Acute Kidney Injury / pathology
  • Adult
  • Aged
  • Antibodies, Antineutrophil Cytoplasmic / analysis*
  • Biopsy
  • Creatinine / blood
  • Cyclophosphamide / therapeutic use
  • Disease Progression
  • Female
  • Glomerulonephritis / complications*
  • Glomerulonephritis / drug therapy
  • Glomerulonephritis / immunology
  • Glomerulonephritis / pathology
  • Glomerulonephritis, Membranous / complications*
  • Glomerulonephritis, Membranous / drug therapy
  • Glomerulonephritis, Membranous / immunology
  • Glomerulonephritis, Membranous / pathology
  • Hematuria / etiology
  • Hematuria / immunology
  • Hematuria / pathology
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / immunology
  • Kidney Failure, Chronic / pathology
  • Kidney Function Tests
  • Kidney Glomerulus / pathology*
  • Kidney Glomerulus / physiopathology
  • Male
  • Middle Aged
  • Necrosis
  • Proteinuria / etiology
  • Proteinuria / immunology
  • Proteinuria / pathology
  • Steroids / therapeutic use
  • Treatment Outcome

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Immunosuppressive Agents
  • Steroids
  • Cyclophosphamide
  • Creatinine