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Hello. I'm David Kavanagh,
Professor of Complement Therapeutics at Renal Complement Therapeutic Center, Newcastle.
Today we are going to discuss the two prototypical renal disorders of complement
over-activation: atypical haemolytic uraemic syndrome and C3 glomerulopathy.
Untreated atypical HUS results in rapidly progressive renal failure.
C3 glomerulopathy usually presents with
nephrotic syndrome and slowly progressive renal failure.
I will also briefly discuss age-related macular degeneration the commonest cause of
blindness in the developed world which shares many of
the same genetic and acquired complement risk factors.
Haemolytic uraemic syndrome is a triad of microangiopathic haemolytic anemia,
thrombocytopenia, and acute renal failure.
Here you can see a blood film showing schistocytes and the lack of platelets.
Below is a renal biopsy demonstrating
footprints from by obliterating the capillary lumen.
There are two forms of haemolytic uraemic syndrome.
By far the commonest form is Shiga toxin associated
HUS which accounts for about 90 percent of cases.
This is caused by infection with Shiga toxin-producing E. coli.
Most commonly in the UK,
this is E. coli, O157:H7.
In developing countries, Shiga can also cause S disease.
Shiga toxin associated HUS has a relatively good prognosis with
only five percent developing end-stage renal failure under mortality of only 1-3 percent.
In contrast, atypical HUS is much rarer with an incidence in
the UK of about 0.4 per million population per year.
It can be familiar or sporadic.
Historically, it has a poor prognosis with about 25 percent of patients
dying in the acute episode and about half developing end-stage renal failure.
Additionally, renal transplantation was
impossible as this disease rapidly recurred in transplant.