Systemic renal Flashcards
If you had to break small vessel vasculitis into two categories, what would they be?
Typically we talk about:
- pauci-immune (no immune complexes on IF)
- immune-complex mediated
What are a couple of causes of pauci-immune vasculitis?
This is another name for the ANCA associated vasculidites.
Microscopic polyangiitis
Wegener’s granulomatosis (now known as granulomatosis with polyangiitis)
Churg-Strauss syndrome
Drug-induced ANCA associated vasculitis (hydralazine, penicillamine, PTU)
Atypical ANCA is associated with IBD
What are some causes of immune-complex renal vasculitis
this list is not exhaustive:
cryoglobulinaemic vasc
HSP (IgA)
Infection - induced immune complex vasc - Hep C, endocarditis
SLE
Rheumatoid vasculitis
Serum sickness vasculitis
Behcet’s disease
Drug induced immune-complex vasculitis
How on earth does ANCA cause disease?
They are antibodies against the neutrophils, and it causes activation of these cells!
The activated neutrophils then adhere to endothelial cells and release inflamm mediators
It is crucial (for understanding of immunofluorescence) that you understand that ANCA is NOT in the kidney. It is the neutrophils that cause disease. There is no immune complex deposition
What are the ANCA-associated disease syndromes?
Overall the renal pathology is similar.
WG - necrotising granulomatous disease often involving the resp tract. Can also have sinusitis, rhinitis, otitis media and ocular inflammation.
Horrible granulomatous lesions in the lungs
Microscopic polyangiitis
Churg-Strauss - associated with asthma, eosinophils and to lesser extent, necrotising granulomatous inflammation
idiopathic necrotising GN
All of WG, CS and MP can be associated with pulmonary haemorrhage
What is the crucial finding on renal biopsy test for ANCA vasculitis?
There are no deposits on the immunofluorescence.
IF stains are for IgA, IgM, IgG, C3, C1q
What is the treatment of lung haemorrhage of ANCA assoc vasculitis?
Plasma exchange may be beneficial in this setting
obviously supportive treatment also essential
Can you think of any other situations with ANCA vasc where plasma exchange has emerging evidence?
in dialysis dependent renal disease
What is the treatment of ANCA-vasculitis?
Immunosuppression is the name of the game. We go for hardcore induction first.
IV ‘roids and cyclophosphamide
Then for maintenance we switch to pred and aza or pred and MMF
Ritux may have a place, particularly in relapsed disease
What are the major complications of cyclophosphamide?
The most important for patients is gonadal toxicity
for men, the cumulative toxic dose is 100mg/kg
for women, the toxic is 200mg/kg
women who receive this treatment who are older than 30 frequently become menopausal
It is also teratogenic
It causes bone marrow suppression
It causes nasty infections - PCP, nocardia, TB and HPV
There are malignancies associated - bladder CA, skin, lymphoma
What is Anti-GBM disease?
This is also known as Goodpasture’s disease.
It is GN +/- pulm haemorrhage
It is a well-described antibody to type IV collagen (chromosome 2)
The antibody is pathogenic. It can even reach levels of 1% of circulating IgG!
It binds rapidly to the GBM with high affinity and can cause fulminant disease
It is believed that there needs to be an environmental stimulus for the pulm haemorrage (e.g. smoking will damage the lung ever so slightly and set it all off)
What do we see on histology in the setting of Goodpasture’s?
We see focal and segmental GN.
There is leucocyte infiltrate and segmental necrosis
Crescents will be visible
Destruction of GBM will be seen
On IF, linear IgG will be seen
How do we treat anti-GBM disease?
Plasma exchange is best
then immunosuppression - ‘roids and cyclophos
if you can turn the disease off, then it’s about the prior damage.
if dialysis dependent at presentation, then never get off
Which of the antibodies are strongly associated with SLE nephritis?
anti-dsDNA and anti-SM Ab are strongly associated
are the sero-neg and drug associated lupus more, or less, associated with renal involvement?
they tend to have little renal involvement.
does renal nephritis stay at the same stage, or switch from one to another?
it can do anything. people without involvement can get involvement, and people can switch from stage to stage.
Describe the pathogenesis of SLE?
Overall it is an immune complex GN.
The complexes are formed from DNA-antiDNA, C1q, Ro, chromatin, laminin
The big complexes and negatively charged complexes seem to bind to subendothelial - this represents class III or IV nephritis
The positive seem to bind to epithelial and create a more indolent membranous pattern (V)
It may come to pass that we find out that IgG subclass will be important.
What do we see on renal biopsy in stage III/IV lupus nephritis?
this is a proliferative GN
this is the “full house” of immune deposits (IgG, IgA, IgM, complement etc).
these patients also often have high serological titres
The biopsy will also show cellular prolif, crescents, PMNs, “wire loops”
fibrin and thrombi and necrosis too
What is the prognosis of SLE nephritis Class IV?
what about recurrence post transplant?
complete remission is 25-85% at 12 months! (complete is <0.5g/day proteinuria)
ESRF 2 - 20% at 5 years
relapses are common. depends on disease activity. poor compliance associated with relapse (WHAT A SURPRISE!)
recurrent post transplant is about 30%, but rarely causes graft loss
prognosis of renal survival is much better if you can get patient into remission (95 v 60% at 10 year)
What is the treatment of Class IV lupus nephritis?
Induction therapy (3-6 months):
- IV or oral glucocorticoid
- oral MMF OR: IV cyclophosphamide
Maintenance:
oral glucocorticoid, oral MMF with plan to step down to oral Aza once stable
there is emerging evidence that plaquenil is useful in maintenance too
what are the benefits of oral mycophenolate v cyclophosphamide in the SLE population
when would you elect for cyclophos?
There were many benefits, from less leucopenia, to better achievement of remission.
However, given the population that often suffers SLE nephritis - MMF was less associated with amenorrhoea cf cyclophos
according to Dr Van Eps, you would look towards cyclophos if the disease was very severe. (I’m not sure if this is because of lack of data, or weaker mech of action)
What is the histopath of class IV SLE nephritis?
What is the treatment?
It is also known as membranous lupus nephritis. It looks almost the same as idiopathic membranous, but with idiopathic IF shows IgG and maybe some comp, and class V lupus has “full house”
treatment in bad disease is same as class IV - cyclophos and aza or MMF
if okay, then calcineurin inhibitor
NOTE: this is different treatment to idiopathic membranous
What is the clinical triad of haemolytic uraemic syndrome
clinical triad of renal failure, microangiopathic haemolytic anaemia and thrombocytopenia
What are the types of HUS?
- diarrhoeal (typical) - Shiga toxin
- E coli
- Shigella toxin - non-diarrhoeal (atypical)
- infection - pneumococcus, Q fever, HIV, CMV
- drugs - cyclosporine, OCP, cisplatin, bleomycin
- radiation
- pregnancy (?is it therefore oestrogen dependent?)
- familial/sporadic
What is the long term prognosis of typical HUS?
recovery of renal function seen in 95% of cases
about 50% had CKD in the Adelaide outbreak
