Rapidly progressive renal failure followed by respiratory failure in an elderly woman

Article history: Received: 2 April 2017 Accepted: 25 May 2017 Published online: 23 June 2017 DOI: 10.15171/jnp.2017.55 Implication for health policy/practice/research/medical education: Patients with dual positive antibodies of anti-GBM antibody and ANCA antibody, have a poor prognosis and behave more like anti-GBM disease than vasculitis. The prognosis of such patients is poor. Please cite this paper as: Naqvi R, Mubarak M. Rapidly progressive renal failure followed by respiratory failure in an elderly woman. J Nephropathol. 2017;6(4):346-348. DOI: 10.15171/ jnp.2017.55.


Questions
Describe the X-ray chest findings.Describe the renal biopsy findings.Describe the lung biopsy findings.What is the significance of dual positivity of anti-GBM and ANCA in crescentic glomerulonephritis (CresGN)?Describe the management of the condition.

Describe the X-ray chest findings
The first X-ray chest (Figure 1 A) shows clear lung fields.No focal mass or opacification is noted.However, the second chest roentgenogram (Figure 2A) is grossly abnormal and shows diffuse alveolar shadowing of both lung fields.This appearance is seen in a limited number of conditions, including diffuse pulmonary edema, adult respiratory distress syndrome (ARDS) and diffuse alveolar hemorrhage.The findings in our case reflect diffuse alveolar hemorrhage, as the other causes were ruled out by history and lack of improvement on ultrafiltration.

Describe the renal biopsy findings
Renal biopsy was adequate with up to 38 glomeruli.All of these were grossly abnormal and showed crescent formation.Majority of the crescents (n = 23) were cellular (Figure 1B), 11 were fibrocellular (Figure 1C), and four were fibrous.There was no vasculopathy or vasculitis of the vessels included in the biopsy.
There was moderate degree of tubular atrophy and interstitial inflammation.A few tubules also showed necrotic debris and neutrophils in the lumena.IF for IgG showed diffuse strong (3+) linear positivity along GBM, while the crescentic proliferation was negative (1D).The renal biopsy findings, especially the polyphasic nature of crescents, suggest that the glomerular lesions are primarily caused by ANCAassociated pathology, with superimposed anti-GBM antibody nephritis.

Describe the lung biopsy findings
The needle biopsy of the lungs done postmortem showed intra-alveolar fibrin deposition and hemorrhage.In addition, alveolar walls also showed evidence of capillaritis and hemorrhage (Figure 2B).These findings are consistent with the lung involvement in Good pasture's syndrome.There was also hypertrophy of type II pneumocytes.No infective organism was found.No viral inclusions were seen.

What is the significance of dual positivity of anti-GBM and ANCA in CresGN?
The serologic evidence of double positivity for both ANCA and anti-GBM antibodies is fairly common in patients with either antibody and a clinical picture of rapidly progressive GN (RPGN) (1,2).Up to 20-25% of patients with anti-GBM antibody nephritis have associated ANCA positivity (3).On the other hand, 5% of ANCA-associated GN patients have anti-GBM antibodies in their sera (4).Interestingly, our patient had both types of ANCA antibodies, a phenomenon very rarely reported in literature.Some studies have shown that patients with dual positive antibodies have a poor prognosis when presenting with severe disease and behave more like anti-GBM disease than vasculitis (3).Other authors have suggested that these patients behave as vasculitis-variant of anti-GBM antibody nephritis (4).Presumably, the predominant behavior depends on the predominance and primacy of either antibody.The recovery of renal functions is rare with dual positivity of the above markers.

Describe the management of the condition
There are three main tenets of treatment of anti-GBM antibody nephritis; removal of the antibody from the circulation by plasmapheresis; prevention of further antibody production by the immunosuppression; and eliminating or avoiding future exposure to potential triggering agents.However, the key to successful treatment is the early diagnosis and institution of therapy.Delay in these often leads to fatal outcome as in our case.

Final Diagnosis
Anti-GBM antibody associated nephritis complicating ANCA-associated disease.

Figure 1 .Figure 2 .
Figure 1.Chest X-ray at the time of admission and renal biopsy findings on light microscopy and immunofluorescence.