Case 17: Diagnosis & Conclusions

Case 17 Index

Diagnosis: Anti-Glomerular Basement Membrane (GBM) Disease (Goodpasture’s Disease) 

Case Summary:

Nice work! Let’s break it down, starting from the HPI. We start off with a previously healthy man with no known past medical history now presenting with hypertensive emergency (markedly elevated blood pressure with visual symptoms and papilledema suggestive of elevated intracranial pressure) and peripheral edema. We see that his creatinine is 4.9 mg/dL (presumably normal before)– thus, we are dealing with an acute process.

The physical exam tells us he has evidence of volume overload (peripheral edema). A differential at this point would include rapidly progressive glomerulonephritis (RPGN, given the likely rapid rise in creatinine) and hypertensive emergency.

Classification of RPGN (click below!)
Anti-glomerular basement membrane disease
Also known as Goodpasture’s disease, typically affects the small vessels of the kidney and lung and can be diagnosed by biopsy and an elevated anti-GBM antibody titer.
Immune-complex mediated
Can be secondary to wide variety of immune-complex mediated disease including systemic lupus erythematosus (SLE), hepatitis C virus, IgA nephropathy, post-infectious glomeruonephritis, etc.
Pauci-immune
Usually ANCA associated, and named because of the absence of immune complex deposition (absence of deposits on electron microscopy and negative immunofluorence)

Let’s take a look at the laboratory data. The urinalysis shows us red blood cells, red blood cell casts, fatty oval bodies, and nephrotic range proteinuria – suggestive of glomerular injury and a mixed nephrotic and nephritic syndrome. Hypertensive emergency leads to vascular injury and less likely to present with nephrotic range proteinuria (though microscopic hematuria may be present). The absence of white blood cells (pyuria) makes acute interstitial nephritis less likely.

Negative ANCA titers make pauci-immune disease less likely, and normal complement levels lower proliferative SLE nephritis, mebranoproliferative GN, and post-infectious GN on our differential. The kidney ultrasound shows a normal kidney with normal size and echogenicity, and no hydronephrosis.

The clinical picture and crescent that we see on light microscopy confirms our suspicion of RPGN. The clincher for this diagnosis is the IF stain – we see the classic linear staining of IgG. If you ever see this ribbon-like, smooth staining on IF, think anti-GBM disease! On electron microscopy, we would not expect to see any deposits but would likely see podocyte effacement given the presence of proteinuria and breaks in the basement membrane (seen with crescent formation).

Anti-glomerular basement membrane disease (anti-GBM or Goodpasture’s disease) is a rare cause of autoimmune glomerulonephritis, with  antibodies against the NC1 domain of  α3 chain of type IV collagen – which is present in both the glomerular and alveolar basement membranes. A pathologist Ernest Goodpasture first described this disease in 1919 – use the “G” to remember that there is most often linear staining of IgG on IF.

The treatment? Get rid of the antibodies (plasmapheresis)  + immunosuppressive therapy (glucocorticoids and cyclophosphamide). Anti-GBM antibody titers should be monitored to ensure clearance.

Up to 40% of patients with anti-GBM disease may also test positive for ANCA antibodies (usually anti-myeloperoxidase or p-ANCA)! Remember to check for these, as presence can inform the treatment plan.

Look out for anti-GBM disease in patient’s with X-linked Alport’s syndrome following a kidney transplant! Why? Patients with Alport’s syndrome have a mutation in the α5 (not 3 as above) chain of type IV collagen – and thus may have circulating antibodies against the α3, α4, or α5 type IV collagen chains. Finally, AD (autosomal dominant inheritance) Alport’s patients typically have mutations in the α3 or α4 chains.

For a more, take a look at the references below:

  1. Fogo AB, Lusco MA, Najafian B, Alpers CE: AJKD Atlas of Renal Pathology: Anti-Glomerular Basement Membrane Antibody-Mediated Glomerulonephritis. Am. J. Kidney Dis. Off. J. Natl. Kidney Found. 68: e29–e30, 2016
  2. Kluth DC, Rees AJ: Anti-Glomerular Basement Membrane Disease. J. Am. Soc. Nephrol. 10: 2446–2453, 1999
  3. McAdoo SP, Pusey CD: Anti-Glomerular Basement Membrane Disease. Clin. J. Am. Soc. Nephrol. CJASN 12: 1162–1172, 2017

Case 17 Index
Case 17 Introduction
Case 17 Physical Exam
Case 17 Diagnostic Testing
Case 17 Pathology
Case 17 Additional Pathology
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