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. Okay. D dot org slash podcast. Thank you for listening.