GLOMERULONEPHRITIS QUIZ

The answer to the GN Quiz June 21, 2012: the biopsy showed anti-GBM nephritis (see images, CLICK OVER IMAGE TO ENLARGE).

The Question

73-year-old woman presents with hematuria and ARF. Serum creatinine is 10.2 mg/dl.  BP 160/62.  P-ANCA positive. She gives history of hemoptysis in 2005.  What will the renal biopsy show?

ANCA+ with anti-myeloperoxidase titers:

6/14/05        26 units

8/17/05        5.4 units

10/18/05      1.3 units

12/13/05      <1.0 units

11/07/06      1.3 units

05/08/07      2.3 units

08/14/07      16 units

11/25/08      155 units

02/10/09      26 units

05/15/09      15 units, two days after the biopsy   

Discussion

• All patients with anti-GBM antibody nephritis should be tested for ANCA.
• 20–25% of patients with anti-GBM nephritis also have ANCA antibodies known as WHO type IV crescentic disease.
• The majority of reported cases with dual antibodies are 50 to 80 years of age, which corresponds to the typical age of patients with ANCA-associated disease.
• In contrast, anti-GBM nephritis has a bimodal distribution, typically occurring in males in their 20 s and women >80 years old.
• Previous studies have noticed a prevalence of anti-GBM antibodies in 5% of ANCA vasculitis cases. Therefore, it is possible that many elderly patients with anti-GBM nephritis (second peak of bimodal curve) may in fact have ANCA vasculitis with superimposed anti-GBM antibody nephritis, as ANCA vasculitis is signficantly more common.
• One pathophysiological hypothesis regarding anti-GBM antibody formation is the p-ANCA injures of the glomerular basement membrane during crescent formation, exposing de novo basement membrane antigens and initiating development of an anti-GBM antibody.
• In vivo experiments have demonstrated that MPO-ANCA can severely aggravate subclinical anti-GBM glomerular disease in rats.
• It is unknown why only a small percentage of ANCA vasculitis patients develop anti-GBM antibodies, but this may relate to associated factors including the presence of underlying renal disease, smoking, infection, or environmental and genetic factors.
• Patients with dual antibodies may have an atypical presentation, which may cause delay in the correct diagnosis and initiation of treatment.
• Some clinical features of vasculitis including arthralgias, rash, malaise, and fever may occur in these patients, while typically are absent in classic anti-GBM nephritis.
• Patients with persistence of ANCA after resolution of the initial symptoms have a higher incidence of recurrence and need close monitoring of ANCA levels.
• Unlike classic anti-GBM cases, such patients should be treated with long-term maintenance immunosuppression such as azathioprine, methotrexate, or low-dose prednisone. 

(Source for discussion Tariq Javed Case Reports in Nephrology 2012 (2012),doi:10.1155/2012/132085)