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Welcome to this episode of que 
digo conversations in Nephrology

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this episode titled is there 
still any role for plasma 

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Exchange in aav is provided by 
KD go and supported by Amgen, 

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here's your host dr. 
Vladimir tesser. 

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Hello and welcome to Katie. 
Got conversations in Nephrology.

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I am dr. 
Vladimir dress ahead of 

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nephrology at General University
Hospital in Prague and joining 

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me to discuss the role of plasma
Exchange in Ankara Associated. 

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Vasculitis is Doctor, Michael 
Walsh microbe is a nephrologist 

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at st. 
Joseph's healthcare Hamilton. 

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And an associate professor in 
the department of medicine and 

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health research, methods, 
evidence and impact at McMaster 

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University in In Hamilton 
Canada, his research interests 

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include a treatment or thank 
associated with colitis, 

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cardiovascular. 
Complications of chronic kidney 

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disease and symptoms of chronic 
kidney disease. 

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He was also the main 
investigator on the recently 

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published by activist trial, the
largest-ever randomized control 

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trial in Ankara associated with 
collided, which studied the role

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of plasma exchange. 
As I don't read mind in patients

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with severe renal. 
Anchor associated with colitis 

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Michael. 
Welcome to the Graham, thank you

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so much Vladimir. 
And also to the Kata organizers,

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we're doing on this series. 
It's a real pleasure to be here.

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Thank you very much. 
So let's begin our discussion 

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with the first question, 
taxable, study suggested. 

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There was no benefit of using 
plasma exchange inpatient, save 

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it, anchor Associated 
vasculitis, and kidney disease, 

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or Alberto Hemorrhage. 
Despite that the catechol 

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guidelines still suggest to use.
Plasma Exchange in patients, 

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with serum creatinine, over 500.
Micro moles per liter. 

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How do you reconcile this 
apparent discordance? 

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That's a great question. 
Vladimir just to clarify pixie 

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vas was designed, try and 
demonstrate whether or not there

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is a benefit of plasma exchange 
on a composite outcome of 

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all-cause mortality or 
institute's kidney disease. 

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And we didn't show a benefit in 
this composite outcome. 

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In these patients, who had 
severe ankle Associated 

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vasculitis, which we 
characterized as either reduced 

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kidney function or diffuse 
alveolar. 

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Hemorrhage there is an important
point to remember, though, In 

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that the primary outcome and the
outcome upon, which we based our

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statistical, power was a 
composite. 

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We use this composite of death 
and kidney failure because 

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they're both very important to 
patients and clinicians and 

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they're both highly correlated 
with one another and similarly 

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common, in patients with severe 
ankle Associated vasculitis. 

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And really importantly, we 
believed that the treatment 

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would have a similar effect on 
both death and kidney failure 

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given long enough, follow-up. 
That's to say that we thought 

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the effects of plasma Exchange. 
Change on kidney function, would

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translate to a survival 
Advantage. 

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Later on what we found though, 
when we first of all, did Peck, 

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see vast and then combine, the 
taxi vast data with other 

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randomized, trial data that 
examined, the role of plasma 

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exchange and ank, Associated 
vasculitis that we published in 

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the bmj earlier this year. 
Was that the beneficial effect 

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on kidney failure? 
Was present, but there was no, 

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or maybe only a trivial effect 
on death. 

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Furthermore, the effects on 
kidney failure appeared to wane 

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over time, we could see it. 
One year but we couldn't really 

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see it anymore. 
By the time, an average of three

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years, follow-up had passed 
because of those issues pecs 

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enas was actually very 
underpowered to find this 

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particular benefit of the 
effects of plasma exchange on 

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kidney function alone and that's
maybe why it's not so surprising

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in retrospect that the results 
were neutral the meta-analysis. 

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On the other hand found a fairly
large or at least moderate 

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effect of plasma exchange on 
kidney failure. 

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It also, identified that there 
is a harmful effect in terms, As

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of an increased risk of 
infection, but we hadn't 

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anticipated. 
So I think plasma exchange does 

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still have a role but it needs 
to be very carefully. 

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Considered the patient's most 
likely to derive benefit, are 

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those who are at high risk of 
kidney failure, but a low risk 

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of infection codigo guidelines. 
Do suggest the plasma Exchange 

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in patients at very high risk of
kidney failure. 

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Defined by being on dialysis, or
at least a creatinine of over 

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500 micro moles per liter and 
there are some other patients 

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that are likely to benefit, or 
at least that they may want the 

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Risk reduction in terms of 
kidney failure, and the 

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potential benefits of plasma 
exchange and are willing to 

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undergo plasma exchange, despite
the possible risks of severe, 

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kidney failure, or severe 
infection, but those need to 

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probably be discussed with 
patients individually. 

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Thank you very much for this 
explanation and my second 

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question concerns renal biopsy. 
So how does a little biopsy help

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select patients that might 
benefit from plasma Exchange? 

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thanks a lot and I think this 
has been a bit of a Hot Topic 

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since taxi vas, we didn't 
require the use of a renal 

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biopsy for patients to enter 
packs Eve as the nephrologist 

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instinctively, know that renal 
biopsies help us understand the 

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prognosis of patients with 
kidney disease and a lot of that

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prognostic information really 
comes from the degree of global 

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sclerosis and interstitial 
fibrosis seen on the biopsy as 

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such you might expect the 
patients that the really 

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Advanced fibrosis who are very 
likely to develop kidney 

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failure, but they may also be be
unlikely to respond to 

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treatment. 
The so-called point of no return

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for those patients, plasma 
exchange or any other effective 

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treatment to reduce the risk of 
kidney failure. 

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May actually offer no benefits 
and may still expose them to the

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risks of the therapy just 
because they're so finebros that

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they have no possibility of 
Return of kidney function or 

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dialysis Independence. 
Having said that, there really 

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isn't a lot of empiric data to 
Define how much fibrosis or 

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sclerosis, creates the point of 
no return. 

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In fact, an anchor Associated 
vasculitis even patients defined

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as having the most advanced 
fibrosis still have a chance of 

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recovery. 
And even when we incorporate 

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biopsy information into 
prediction scores like the one 

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proposed by dr. 
Bricks, one cannot quite Define 

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a patient with a really, really 
high chance of kidney failure. 

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And it does not determine 
whether, or not there is 

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actually a change in the 
protection offered by plasma 

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exchange. 
So how do we incorporate it in 

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the end? 
I think we need to try and Use 

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an overall estimation of the 
prognosis for kidney failure. 

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And there may be some patients 
in which we get a better sense 

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that there may have passed, the 
point of no return and it's not 

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useful to draw for therapies, 
like Plex because they also 

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increase the risk of harmful 
side effects. 

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That's about as as accurate and 
answer is. 

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I think we can get at this time.
There's more research required 

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really to help Define this and I
say, thanks, odo's just you 

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didn't, you are listening to 
Katy. 

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Go conversations in ethology and
how to today's topic is, is 

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there any role for plasma 
Exchange in Ankara Associated 

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vasculitis? 
I am dr. 

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Vladimir Tessa and I am speaking
with dr. 

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Michael Walsh. 
Now as I understand it, Michael,

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there is also a limited place 
for plasma Exchange, in 

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patients, with uncut associated 
with colitis and I'll below 

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Hemorrhage. 
So my sword question is, do you 

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perform plasma Exchange in all 
patients with other hemorrhage? 

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That's a great question about 
America. 

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And I can say quickly, no, I do 
not perform plasma exchange and 

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all patients with alveolar, 
Hemorrhage. 

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As you know, this has been a 
really contentious issue. 

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There's a lot of variation 
between centers, even before 

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pecs Eve asked about what is 
actually done in terms of 

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providing plasma exchange, to 
all some or no patients who have

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alveolar Hemorrhage. 
And I think to really understand

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where we go. 
Next, we need to First Define 

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the goal of offering plasma 
exchange, the usual Paradigm 

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that I hear of is that patients 
with Lung Hemorrhage or at high 

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risk of death. 
I want to challenge that because

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there's been recent work that 
we've done with dr. 

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Lynn Fastener from the pixie 
vast data, as well as older work

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that we did with you, vast data 
that suggest that patients that 

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have non severe. 
Lung Hemorrhage are really not 

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at an increased risk of death, 
compared to those without. 

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So if you accept this, then 
there would be no reason to 

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escalate therapy over the 
standard of care for patients 

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with non severe lung Hemorrhage.
The same issue is not however 

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true for patients a severe lung 
hemorrhage. 

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I have an increased risk of 
death and again dr. 

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Foster's work help support this.
We hope to see in publication 

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soon. 
So then the next question is 

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does plasma exchange reduce that
risk of death. 

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So from both Tech, sieve a sin 
from our meta-analysis. 

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There's really no convincing 
evidence that plasma exchange, 

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reduces the risk of death in the
subgroup of patients with 

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alveolar Hemorrhage or in the 
overall patient population. 

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However, we are fairly 
confident, the plasma exchange 

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increases the risk of serious, 
infections and infections are 

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the most And cause of death in 
patients, with severe, lung 

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Hemorrhage, thanks to advances 
in support of Rafi. 

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Rhetoric are so, I don't provide
plasma exchange for alveolar. 

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Hemorrhage in patients with 
Hank, Associated vasculitis, 

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when that's the sole indication.
Rather we provide it for 

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patients who have alveolar 
Hemorrhage, who are at also risk

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of kidney failure. 
In other words, I based the 

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decision on providing plasma 
contains on the risk of kidney 

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failure. 
And sometimes that includes 

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patients available or Hemorrhage
and many times, it does not 

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Thank you. 
There is a important subgroup of

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patients with double positivity 
of uncle and aunty GPM and it is

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usually recommended that these 
patients should be treated in 

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the same way as other patients 
with Auntie GBM disease. 

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So it's plasma exchange 
mandatory in all patients with 

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double positive anchor and 
anti-gm This is, of course a 

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really difficult question to try
and answer. 

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There's no our CT data to 
support or refute the utility of

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plasma exchange for these 
patients and their likely never 

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will be. 
And in fact, even the 

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observational data is pretty 
small. 

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So my Approach is typically to 
try and face this decision on 

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the most aggressive treatment 
guidelines, which are those 

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prayers are for Angie GBM 
disease or plasma exchange, is 

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typically utilized unless the 
patient has both Advanced 

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sclerosis and fibrosis on the 
original buyer. 

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Oopsie and a very high 
creatinine requires dialysis and

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for many patients also based on 
whether or not they are all 

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Acura. 
Some of those patients may have 

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a more clear phenotype of being 
anchor. 

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Associated vasculitis, others 
may appear to be more clear 

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phenotype of anti GBM disease 
where they really just have a 

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pulmonary renal syndrome or 
renal limited disease. 

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I think it's fair to use the 
anti GBM guidelines and have an 

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open discussion with patients 
about the likely risks and 

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benefits, and their particular 
case, even though this requires 

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Utilizing indirect evidence and 
extrapolating from to diseases. 

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So, I'm sorry, it's not a very 
clear answer, but I would say 

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that I tend to use plasma 
exchange for those who have this

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overlap syndrome Evancho and 
anti GBM disease and we tend to 

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use the same kind of criteria 
for. 

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Not offering it for patients who
look like they're very unlikely 

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to respond to therapy and may 
have harm from it. 

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Thank you very much. 
There is now more and more 

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commonly use rituximab in 
relations with relapsing and 

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also it new only diagnosed 
anchor Associated vasculitis. 

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So my last question concerns 
rituximab how to use rituximab 

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in patients treated also with 
plasma exchange. 

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Thanks by American. 
This is something that I think 

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is really come to the Forefront 
in the last few years is 

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rituximab use has increased 
dramatically for the treatment 

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of these patients. 
When we designed pecks Eve, as 

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we didn't really have much data 
on this and there weren't as 

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many patients not nearly as many
patients. 

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Being treated with rituximab, we
tried to make some kind Of 

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rudimentary guidance. 
And that we told patient, every 

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told providers not to perform 
plasma exchange within 48 Hours 

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of having infused rituximab. 
There wasn't much to guide it. 

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There's pharmacokinetic studies 
that show. 

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Very clear reduction in the 
half-life of rituximab. 

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When plasma exchange is done 
sooner than 48 hours after an 

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infusion, but there isn't very 
much data at all on the 

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pharmacodynamics and how they're
affected by plasma exchange and 

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essentially no data on clinical 
efficacy. 

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From the taxi vast data. 
There was no interaction between

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the use of rituximab and plasma 
exchange. 

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But that doesn't tell us that 
talk. 

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Some about efficacy was 
introduced by the use of plasma 

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exchange. 
It just tells us that it wasn't 

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any different whether or not we 
performed plasma exchange. 

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So I think that's pretty 
reasonable advice. 

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Still, I do think we need to 
think fairly carefully about 

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additional treatment with 
rituximab in patients, who have 

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refractory disease, who receive 
both for toxin table and plasma 

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Exchange. 
But we kind of Base those on 

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each patient individually, 
rather than coming up with any 

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sort of uniform decisions about 
how we would use rituximab. 

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So for right now, we still just 
wait to 48 hours after infusing 

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rituximab before Roots. 
Do another treatment. 

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The plasma exchange - thanks and
before we close Michael out 

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there, any final messages or 
takeaways? 

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You'd like to leave with our 
listeners? 

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Now I think the decision to use 
piles May exchange is still a 

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bit confusing and not unlike 
before. 

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Apex Eve, as before other large 
trials, in the area, like me 

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pack, we really need to base the
decision based on the patient's 

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risk of kidney failure and our 
goal to reduce that risk using 

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plasma exchange. 
So that means we need to be very

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cognizant of what the actual 
risk of kidney, failure is and 

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prognostic scores are becoming 
available to help us try and 

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Define that wrist. 
At the same time, we do need to 

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be aware and vigilant for 
serious infections, which is the

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Common cause of death, for 
patients of anchors, with thank 

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Associated vasculitis, and by 
the fact that for many of us, 

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there are costs and 
inconveniences to the treatment 

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that can also affect the 
patient. 

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But if we put all this 
information together, I think we

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can have actually a really good 
conversation with patients 

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around whether or not the 
treatment should be useful for 

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them and we can make a really 
informed decision. 

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Now there's a great way to round
out our discussion today. 

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I want to thank my guest, dr. 
Michael Walsh for joining me, 

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Michael, it was really great. 
Great having you on the program.

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Thanks so much. 
Bottom are really enjoyed it and

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all the best for the success of 
this podcast series. 

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Go, I'm dr. 
Valerie Mathis. 

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How to access this and other 
episodes in our series. 

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Visit Katie. 
Go on Spotify. 

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Okay. 
D dot org slash podcast. 

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Thank you for listening.