Goodpasture’s Syndrome in old terms.
Again, one of these very renal specific diseases that can likewise cause pulmonary haemorrhage in 40-60% of cases.
Sometimes, it is easier to understand the mechanism of the disease in the first instance.
So, for whatever reason : idiopathic; a chest infection that causes damage to the pulmonary lining – hence revealing an epitope that triggers the Ab to be formed; damage to the GBM with urinary tract obstruction or lithotripsy; genetic susceptibility : HLA-DR15 (confirmed in Chinese and Japanese population and DR4 appear to be at increased risk, while those with DR1 and DR7 are at lesser risk; causes anti GBM Ab (typically IgG 1 or 3 but can also be IgA or IgM) to be made which targets type 4 collagen. If you really want to know – the NC1 domain of the alpha 3 chain -stop being a nerd. Well, they bind most strongly to alpha-3(IV) NC, but the majority also recognized alpha-5(IV) and, to a lesser extent, alpha-4(IV).
So these tiny bastards are floating around your body looking for any basement membrane to bind to and damage it – namely the GBM in your kidneys or alveolar basement membranes in your lungs. BUT!! Patients without alveolar haemorrhage were found to also carry similar autoAb against alpha-3(IV) NC hence some sort of increase in alveolar permeability is required for access to the alveolar basement membrane. Patients with pulmonary haemorrhage were found to have some underlying lung damage – smoking, cocaine inhalation, infections, hydrocarbon exposure —- time to pack them ciggies away and kick the coke habit.
So a patient pitches up – they can become completely anuric and alarm bells should start to ring..
Urine dip can show proteinuria (but not in the nephrotic range) and microscopy show dysmorphic red cells, white cells, red and granular casts.
Chest XRays can show pulmonary haemorrhage and a raised KCO due to increase diffusion across the alveoli because of bleeding.
You panic, stuff in a catheter, get an urgent US to ensure they haven’t completely thrombosesd off their vasculature, take some bloods and send them off for an acute nephritic screen. And the results come back showing raised anti GBM titres but also a positive ANCA. Up to 1/3 of patient with anti GBM have a positive ANCA- mostly MPO-ANCA and blood tests of a batch of military men (they keep their blood many years in advance, why?!) who went on to develop anti GBM disease later showed that they had low levels of ANCA in the past. Mechanism moi? Not sure.
A kidney biopsy is done (of course, ain’t nephrologists for nothing) and light microscopy normally shows a crescentic GN and immunofluorescence – the pathognomonic features of linear IgG deposition along the glomerular capillaries or the distal tubules,
How to treat?
Principle 1 is to get rid of the circulating antibodies. The most efficient way is via plasmapheresis. Quick to do, stick a line in and start.
Principle 2 is to immune suppress. Steroids at 1mg/kg and taper when remission is induced or cyclophosphamide at 2mg/kg and consider azathioprine in the longer term. Of course, our good friend rituximab has also shown to be anecdotally useful.
As a general finding, those with < 30% crescents and a plasma creatinine below 265 micromol/L did well, while those with severe crescentic involvement and a plasma creatinine 354 micromol/L did poorly.
KDIGO guidelines recommend that treatment should be initiated in all patients with
- pulmonary haemorrhage independent of kidney involvement
- anti GBM GN at presentation UNLESS they are dialysis dependant or have 100% crescents on biopsy and do not have pulmonary haemorrhage
- no maintenance IS for anti GBM GN
- to consider transplantation after anti GBM Ab remain undetectable for 6 months
The predictors of kidney survival in anti-GBM GN are
- SCr at presentation
- the need for dialysis at presentation, and the
- percentage of glomerular crescents
Like all autoimmune diseases, this is a shitty one to have as it is aggressive, treatment options aren’t great and although most patients spontaneously go into remission in 12 months, it can reoccur and once ESRF sets it, very few patients come of dialysis.