Welcome to this episode of que digo conversations in Nephrology
this episode titled is there still any role for plasma
Exchange in aav is provided by KD go and supported by Amgen,
here's your host dr. Vladimir tesser.
Hello and welcome to Katie. Got conversations in Nephrology.
I am dr. Vladimir dress ahead of
nephrology at General University Hospital in Prague and joining
me to discuss the role of plasma Exchange in Ankara Associated.
Vasculitis is Doctor, Michael Walsh microbe is a nephrologist
at st. Joseph's healthcare Hamilton.
And an associate professor in the department of medicine and
health research, methods, evidence and impact at McMaster
University in In Hamilton Canada, his research interests
include a treatment or thank associated with colitis,
cardiovascular. Complications of chronic kidney
disease and symptoms of chronic kidney disease.
He was also the main investigator on the recently
published by activist trial, the largest-ever randomized control
trial in Ankara associated with collided, which studied the role
of plasma exchange. As I don't read mind in patients
with severe renal. Anchor associated with colitis
Michael. Welcome to the Graham, thank you
so much Vladimir. And also to the Kata organizers,
we're doing on this series. It's a real pleasure to be here.
Thank you very much. So let's begin our discussion
with the first question, taxable, study suggested.
There was no benefit of using plasma exchange inpatient, save
it, anchor Associated vasculitis, and kidney disease,
or Alberto Hemorrhage. Despite that the catechol
guidelines still suggest to use. Plasma Exchange in patients,
with serum creatinine, over 500. Micro moles per liter.
How do you reconcile this apparent discordance?
That's a great question. Vladimir just to clarify pixie
vas was designed, try and demonstrate whether or not there
is a benefit of plasma exchange on a composite outcome of
all-cause mortality or institute's kidney disease.
And we didn't show a benefit in this composite outcome.
In these patients, who had severe ankle Associated
vasculitis, which we characterized as either reduced
kidney function or diffuse alveolar.
Hemorrhage there is an important point to remember, though, In
that the primary outcome and the outcome upon, which we based our
statistical, power was a composite.
We use this composite of death and kidney failure because
they're both very important to patients and clinicians and
they're both highly correlated with one another and similarly
common, in patients with severe ankle Associated vasculitis.
And really importantly, we believed that the treatment
would have a similar effect on both death and kidney failure
given long enough, follow-up. That's to say that we thought
the effects of plasma Exchange. Change on kidney function, would
translate to a survival Advantage.
Later on what we found though, when we first of all, did Peck,
see vast and then combine, the taxi vast data with other
randomized, trial data that examined, the role of plasma
exchange and ank, Associated vasculitis that we published in
the bmj earlier this year. Was that the beneficial effect
on kidney failure? Was present, but there was no,
or maybe only a trivial effect on death.
Furthermore, the effects on kidney failure appeared to wane
over time, we could see it. One year but we couldn't really
see it anymore. By the time, an average of three
years, follow-up had passed because of those issues pecs
enas was actually very underpowered to find this
particular benefit of the effects of plasma exchange on
kidney function alone and that's maybe why it's not so surprising
in retrospect that the results were neutral the meta-analysis.
On the other hand found a fairly large or at least moderate
effect of plasma exchange on kidney failure.
It also, identified that there is a harmful effect in terms, As
of an increased risk of infection, but we hadn't
anticipated. So I think plasma exchange does
still have a role but it needs to be very carefully.
Considered the patient's most likely to derive benefit, are
those who are at high risk of kidney failure, but a low risk
of infection codigo guidelines. Do suggest the plasma Exchange
in patients at very high risk of kidney failure.
Defined by being on dialysis, or at least a creatinine of over
500 micro moles per liter and there are some other patients
that are likely to benefit, or at least that they may want the
Risk reduction in terms of kidney failure, and the
potential benefits of plasma exchange and are willing to
undergo plasma exchange, despite the possible risks of severe,
kidney failure, or severe infection, but those need to
probably be discussed with patients individually.
Thank you very much for this explanation and my second
question concerns renal biopsy. So how does a little biopsy help
select patients that might benefit from plasma Exchange?
thanks a lot and I think this has been a bit of a Hot Topic
since taxi vas, we didn't require the use of a renal
biopsy for patients to enter packs Eve as the nephrologist
instinctively, know that renal biopsies help us understand the
prognosis of patients with kidney disease and a lot of that
prognostic information really comes from the degree of global
sclerosis and interstitial fibrosis seen on the biopsy as
such you might expect the patients that the really
Advanced fibrosis who are very likely to develop kidney
failure, but they may also be be unlikely to respond to
treatment. The so-called point of no return
for those patients, plasma exchange or any other effective
treatment to reduce the risk of kidney failure.
May actually offer no benefits and may still expose them to the
risks of the therapy just because they're so finebros that
they have no possibility of Return of kidney function or
dialysis Independence. Having said that, there really
isn't a lot of empiric data to Define how much fibrosis or
sclerosis, creates the point of no return.
In fact, an anchor Associated vasculitis even patients defined
as having the most advanced fibrosis still have a chance of
recovery. And even when we incorporate
biopsy information into prediction scores like the one
proposed by dr. Bricks, one cannot quite Define
a patient with a really, really high chance of kidney failure.
And it does not determine whether, or not there is
actually a change in the protection offered by plasma
exchange. So how do we incorporate it in
the end? I think we need to try and Use
an overall estimation of the prognosis for kidney failure.
And there may be some patients in which we get a better sense
that there may have passed, the point of no return and it's not
useful to draw for therapies, like Plex because they also
increase the risk of harmful side effects.
That's about as as accurate and answer is.
I think we can get at this time. There's more research required
really to help Define this and I say, thanks, odo's just you
didn't, you are listening to Katy.
Go conversations in ethology and how to today's topic is, is
there any role for plasma Exchange in Ankara Associated
vasculitis? I am dr.
Vladimir Tessa and I am speaking with dr.
Michael Walsh. Now as I understand it, Michael,
there is also a limited place for plasma Exchange, in
patients, with uncut associated with colitis and I'll below
Hemorrhage. So my sword question is, do you
perform plasma Exchange in all patients with other hemorrhage?
That's a great question about America.
And I can say quickly, no, I do not perform plasma exchange and
all patients with alveolar, Hemorrhage.
As you know, this has been a really contentious issue.
There's a lot of variation between centers, even before
pecs Eve asked about what is actually done in terms of
providing plasma exchange, to all some or no patients who have
alveolar Hemorrhage. And I think to really understand
where we go. Next, we need to First Define
the goal of offering plasma exchange, the usual Paradigm
that I hear of is that patients with Lung Hemorrhage or at high
risk of death. I want to challenge that because
there's been recent work that we've done with dr.
Lynn Fastener from the pixie vast data, as well as older work
that we did with you, vast data that suggest that patients that
have non severe. Lung Hemorrhage are really not
at an increased risk of death, compared to those without.
So if you accept this, then there would be no reason to
escalate therapy over the standard of care for patients
with non severe lung Hemorrhage. The same issue is not however
true for patients a severe lung hemorrhage.
I have an increased risk of death and again dr.
Foster's work help support this. We hope to see in publication
soon. So then the next question is
does plasma exchange reduce that risk of death.
So from both Tech, sieve a sin from our meta-analysis.
There's really no convincing evidence that plasma exchange,
reduces the risk of death in the subgroup of patients with
alveolar Hemorrhage or in the overall patient population.
However, we are fairly confident, the plasma exchange
increases the risk of serious, infections and infections are
the most And cause of death in patients, with severe, lung
Hemorrhage, thanks to advances in support of Rafi.
Rhetoric are so, I don't provide plasma exchange for alveolar.
Hemorrhage in patients with Hank, Associated vasculitis,
when that's the sole indication. Rather we provide it for
patients who have alveolar Hemorrhage, who are at also risk
of kidney failure. In other words, I based the
decision on providing plasma contains on the risk of kidney
failure. And sometimes that includes
patients available or Hemorrhage and many times, it does not
Thank you. There is a important subgroup of
patients with double positivity of uncle and aunty GPM and it is
usually recommended that these patients should be treated in
the same way as other patients with Auntie GBM disease.
So it's plasma exchange mandatory in all patients with
double positive anchor and anti-gm This is, of course a
really difficult question to try and answer.
There's no our CT data to support or refute the utility of
plasma exchange for these patients and their likely never
will be. And in fact, even the
observational data is pretty small.
So my Approach is typically to try and face this decision on
the most aggressive treatment guidelines, which are those
prayers are for Angie GBM disease or plasma exchange, is
typically utilized unless the patient has both Advanced
sclerosis and fibrosis on the original buyer.
Oopsie and a very high creatinine requires dialysis and
for many patients also based on whether or not they are all
Acura. Some of those patients may have
a more clear phenotype of being anchor.
Associated vasculitis, others may appear to be more clear
phenotype of anti GBM disease where they really just have a
pulmonary renal syndrome or renal limited disease.
I think it's fair to use the anti GBM guidelines and have an
open discussion with patients about the likely risks and
benefits, and their particular case, even though this requires
Utilizing indirect evidence and extrapolating from to diseases.
So, I'm sorry, it's not a very clear answer, but I would say
that I tend to use plasma exchange for those who have this
overlap syndrome Evancho and anti GBM disease and we tend to
use the same kind of criteria for.
Not offering it for patients who look like they're very unlikely
to respond to therapy and may have harm from it.
Thank you very much. There is now more and more
commonly use rituximab in relations with relapsing and
also it new only diagnosed anchor Associated vasculitis.
So my last question concerns rituximab how to use rituximab
in patients treated also with plasma exchange.
Thanks by American. This is something that I think
is really come to the Forefront in the last few years is
rituximab use has increased dramatically for the treatment
of these patients. When we designed pecks Eve, as
we didn't really have much data on this and there weren't as
many patients not nearly as many patients.
Being treated with rituximab, we tried to make some kind Of
rudimentary guidance. And that we told patient, every
told providers not to perform plasma exchange within 48 Hours
of having infused rituximab. There wasn't much to guide it.
There's pharmacokinetic studies that show.
Very clear reduction in the half-life of rituximab.
When plasma exchange is done sooner than 48 hours after an
infusion, but there isn't very much data at all on the
pharmacodynamics and how they're affected by plasma exchange and
essentially no data on clinical efficacy.
From the taxi vast data. There was no interaction between
the use of rituximab and plasma exchange.
But that doesn't tell us that talk.
Some about efficacy was introduced by the use of plasma
exchange. It just tells us that it wasn't
any different whether or not we performed plasma exchange.
So I think that's pretty reasonable advice.
Still, I do think we need to think fairly carefully about
additional treatment with rituximab in patients, who have
refractory disease, who receive both for toxin table and plasma
Exchange. But we kind of Base those on
each patient individually, rather than coming up with any
sort of uniform decisions about how we would use rituximab.
So for right now, we still just wait to 48 hours after infusing
rituximab before Roots. Do another treatment.
The plasma exchange - thanks and before we close Michael out
there, any final messages or takeaways?
You'd like to leave with our listeners?
Now I think the decision to use piles May exchange is still a
bit confusing and not unlike before.
Apex Eve, as before other large trials, in the area, like me
pack, we really need to base the decision based on the patient's
risk of kidney failure and our goal to reduce that risk using
plasma exchange. So that means we need to be very
cognizant of what the actual risk of kidney, failure is and
prognostic scores are becoming available to help us try and
Define that wrist. At the same time, we do need to
be aware and vigilant for serious infections, which is the
Common cause of death, for patients of anchors, with thank
Associated vasculitis, and by the fact that for many of us,
there are costs and inconveniences to the treatment
that can also affect the patient.
But if we put all this information together, I think we
can have actually a really good conversation with patients
around whether or not the treatment should be useful for
them and we can make a really informed decision.
Now there's a great way to round out our discussion today.
I want to thank my guest, dr. Michael Walsh for joining me,
Michael, it was really great. Great having you on the program.
Thanks so much. Bottom are really enjoyed it and
all the best for the success of this podcast series.
Go, I'm dr. Valerie Mathis.
How to access this and other episodes in our series.
Visit Katie. Go on Spotify.
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