GN in Ten

Board Review Bonus 7: Membranous Nephropathy
In this "Board Review Bonus" (BRB) episode, hosts Dr. Kenar Jhaveri and Dr. Koyal Jain deliver a high-yield clinical overview of membranous nephropathy (MN)—a classic, board-favorite cause of nephrotic syndrome. Utilizing a real-world case of a 50-year-old male presenting with heavy proteinuria and severe hypoalbuminemia, they walk through diagnostic dilemmas, pathological clues, and the modern therapeutic landscape. Whether you are studying for the boards or looking to "class-switch" your clinical knowledge from IgG1 to IgG4, this bite-sized episode is packed with essential clinical pearls.
Key Topics Covered:

  • Epidemiology & Biopsy Basics: Identifying MN as one of the most common causes of adult nephrotic syndrome. The hosts break down classic pathology features: diffuse GBM thickening on light microscopy, "spikes" on silver stain, granular IgG and C3 immunofluorescence, and subepithelial dense deposits on EM.
  • The Antigen Revolution: A review of how the 2009 discovery of anti-PLA2R antibodies on podocytes transformed the diagnosis of primary MN. They also highlight newer antigens to know for the boards, including NELL-1 (associated with malignancy, medications, and lipoic acid), THSD7A (associated with malignancy), and EXT1/EXT2 (associated with lupus).
  • Investigating Secondary Causes: Why age-appropriate malignancy screening, medication reviews, and infectious workups (syphilis, hepatitis B and C) are essential even in PLA2R-positive cases. Key biopsy clues like "full house" staining or endothelial tubuloreticular inclusions can help tip you off to a secondary etiology.
  • The "Koyal-Kenar" Risk Stratification: Why tracking immunological remission via anti-PLA2R titers is often far more predictive than following proteinuria alone. The hosts outline when to initiate immunosuppression based on GFR decline, severe proteinuria/complications, or stable/rising anti-PLA2R titers.
  • Conservative Therapy (The CKD Toolkit): Standard management including low-sodium diets, maximal RAAS blockade, statins (mindful of CNI interactions), SGLT2 inhibitors, and prophylactic anticoagulation (using apixaban or warfarin) when albumin drops below 2.0–2.5 g/dL.
  • The Immunosuppressive Toolkit: Navigating the "big three" regimens: the highly effective but complex 6-month Modified Ponticelli Regimen, first-line Rituximab (backed by the MENTOR trial), and Calcineurin Inhibitors (useful as a bridge, but limited by high relapse rates). Plus, a sneak peek at obinutuzumab (the Majesty trial) for deeper B-cell depletion.
Recommended Literature:

Creators and Guests

Host
Kenar Jhaveri
Chair, ISGD Education Committee. Nephrologist Educator, Rapidly Progressive Glomerular Nephrologist, onconephrologist, cyclist 🚴‍♀️, runner 🏃 Editor in chief: ASN Kidney News
Host
Koyal Jain
ISGD Education Committee Co-Chair | PD @UNCkidney | Director of UME @UNCDeptMedicine | Glomerular Diseases and Vasculitis | Medical Education | Tweets are my own
Producer
Angel Morales
Project Manager @ International Society of Glomerular Disease
ED
Editor
Eric Damashek
GN in 10 Editor

What is GN in Ten?

A bite-size podcast brought to you by the International Society of Glomerular Disease. Nephrologists and glomerular disease experts Dr. Kenar Jhaveri (Northwell Health/Hofstra University) and Dr. Koyal Jain (UNC Chapel Hill) take a lighthearted look at the latest research, discuss clinical practice, and interview leaders in glomerular medicine — all in a short enough time to listen on your coffee break.

BRB 7: Membranous Nephropathy v.4
===

Barbara Gillespie: [00:00:00] Hi everyone. This is Dr. Barbara Gillespie. I'm the chief medical and strategy officer at ISGD. We're thrilled to invite you to attend our inaugural clinical trial summit meeting that takes place on November 13th through the 15th in Galveston, Texas.[00:00:15]

If you've ever thought about glomerular disease trials at all, this is the meeting you've been waiting for. It's the first meeting completely dedicated to our passions, both glomerular health and the critical tools to ensure the success of glomerular disease clinical [00:00:30] trials. Still wondering what the best endpoints and trial designs should be for glomerular disease trials?

Are you tired of settling for enrolling only one GD patient per site? These are just some of the questions that we're gonna answer when we're all under one roof together. Please register at [00:00:45] is-gd.org. Your voice matters

Laurel Damashek: Welcome to GN in Ten a bite sized podcast brought to you by the International [00:01:00] Society of Glomerular Disease. Our hosts are nephrologists and glomerular disease experts. Dr. Kenar Jhaveri of Northwell Health and Hofstra University on Long Island, New York, and Dr. Koyal Jain from the [00:01:15] University of North Carolina Chapel Hill.

Koyal Jain: Hello, everybody. This is Koyal Jain here with Dr. Kenar Jhaveri. We are back with our board review bonus episode on membranous today. And I will also say that you might have [00:01:30] seen a lot of these BRB episodes. It's because they've been really popular, and people have loved them. So we hope that you continue to like this one as well.

Kenar Jhaveri: So today's topic is membranous nephropathy, which has been a hot topic on the boards as well, and lately there have been a lot of changes [00:01:45] in terms of antigen development. We'll focus on the board part of things so if you want, we can start that, Koyal

Koyal Jain: So why don't we start with a case because I think it gives context to what we're talking about here. So I have this [00:02:00] 50-year-old gentleman who was referred to me by another nephrologist for having nephrotic syndrome, about eight to 10 grams of proteinuria, and albumins running around 2.3 - 2.4. So he [00:02:15] comes in, has already had a kidney biopsy which shows membranous. So the first question really is how common is membranous and should we be thinking about race or not with membranous? Is it only in the [00:02:30] white population? Is it not? What do you say, Dr. Jhaveri?

Kenar Jhaveri: it's probably one of the most common nephrotic syndromes that we see in adults, along with FSGS. I see it more frequently in white males, or other white patients compared to African [00:02:45] Americans but it can be seen in both. And I think the age you presented is a classic case for us today. So one thing to keep in mind is that most of these patients have sort of a subacute onset of nephrotic syndrome. It's not a sudden onset. So that's your classic presentation.

[00:03:00] Some of them can have subnephrotic range proteinuria, but usually it's full-blown nephrotic syndrome. And your classic pathology features are - because that's what's gonna be on the boards as well - a diffuse thickening of the GBM, there are these classic spikes of [00:03:15] GBM extending through the immune deposits, in that you see the immunofluorescence will show usually a granular pattern of IgG and C3, and the electron microscopy will have the subepithelial dense deposits on the outer aspect of the [00:03:30] GBM. And you will probably see some foot process effacement. And that's pretty much in a nutshell what you will see on a biopsy, right?

Koyal Jain: Correct. And I wanna make sure I address something that you mentioned. Let's go into a little bit more depth there. We have this GBM [00:03:45] thickening and these spikes, right? So if you're looking at light microscopy, you'll see thickening of the basement membrane, but first you have to stain them with silver staining, and then you can see these spikes.

And so the spikes that you typically will see is the GBM that [00:04:00] is extending in between these immune deposits. And so that is important. The other thing that I really think about when I'm reading a biopsy - and when I say I'm reading a biopsy, I'm not a nephropathologist, but when I get a biopsy, I'll read the whole biopsy report.

And what I will see is often [00:04:15] times primary membranous will have an IgG4 type immunofluorescence pattern, so it's IgG4 predominant. Although you can argue that certain antigens may have certain other IgGs, but PLA2R specifically, primary membranous is typically [00:04:30] IgG4

Kenar Jhaveri: So that brings us to actually 2009. Before 2009, we would call this idiopathic membranous, most of the cases we had . We didn't know the cause. And the secondary causes were the [00:04:45] classics: hepatitis, infections, NSAIDs, malignancy.

We would look for those, and we would say, "Okay, that's secondary now that we found a cause, say it's lupus," and we would assign that to secondary membranous. And primary we just didn't know . And like you [00:05:00] said, there were clues on kidney biopsy, for example, like the type of IgG staining could give us a clue. If there was a full house staining, we knew that was more of a secondary cause rather than primary membranous. But then, in 2009, this really changed nephrology [00:05:15] because a pivotal discovery by folks in Boston showed that the phospholipase A2 receptor positivity was seen in close to eighty to ninety percent of primary membranous.

And that, along with the antigen staining and [00:05:30] the antibody in the serum, really revolutionized the diagnosis of membranous nephropathy.

Koyal Jain: And what is this PLA2R, this phospholipase A2 receptor? So it's actually a transmembrane protein that is present on the podocytes. And if [00:05:45] somebody, let's say, has primary membranous and creates antibodies , these antibodies can go and attack this PLA2R, which is present in the subepithelial portion essentially.

And so that's where they would attack, and that's where you see those deposits right there. And so now on kidney biopsies, [00:06:00] we can basically stain for some of these. Probably not all institutions have the ability to stain for all different types of antigens. But you can stain for at least a couple of them, and then you can send the path slides for mass spec if needed to [00:06:15] figure out what antigen exists.

Kenar Jhaveri: You know, what Koyal is saying is completely accurate, but it's more that....this will likely not be on the boards, but in the last five years, we have also seen a slew of other antigens that have been discovered, and that have shown some classic [00:06:30] associations with some of the old secondary causes we used to see .

So for example , after PLA2R, the next most common is Nell-1, and that's been the classic association with malignancy or medications induced. Then there's thrombospondin, D7A, which is a [00:06:45] classic association with malignancy, and the exotoxin 2, which is a classic association with lupus. So those are the three big other ones that maybe you should know. Then there are a slew of other ones seen in pediatrics. There is a special type seen in neurological [00:07:00] disease-associated membranous and a classic one with syphilis or NSAID-induced membranous. And so there's so many coming out one with stem cell transplant and membranous. So I don't think you need to know all of these yet. But maybe in another ten years, [00:07:15] we might just have a panel that we could order on kidney biopsy staining that could tell us which specific class type of membranous this is and what's the association of that with which clinical syndrome, which is a great move in nephrology, way ahead now [00:07:30] twenty years from when first we found a PLA2R.

Koyal Jain: I will also say that when you're thinking about all these secondary causes like drugs, malignancy or some other autoimmune process that's causing this membranous, also take a look at the [00:07:45] biopsy, right? We talked about the IgG class. We talked about the full house staining. But also, do they have endothelial tubular reticular inclusions? Do they have, proliferative changes, right? Do they have non-subepithelial deposits? Think about the other things that can be favoring [00:08:00] secondary membranous. And then now we can not only stain the biopsy for at least a couple of these, you can also send for a commercial membranous nephropathy panel or cascade, depending on what commercial lab you use, and they can spit out a number telling you what is a [00:08:15] PLA2R antibody titer or the thrombospondin titer.

Kenar Jhaveri: And even if you do have these stainings, most centers these days have a PLA2R staining that'll be done on their pathology specimen. But the other stainings are gonna be a special ask. So you might not think about [00:08:30] it, you might not ask for it, a pathologist might not do it.

So as a result, it's good practice to always look for secondary causes of any glomerular disease. Even if it's PLA2R positive, before you start treatment, you might wanna make sure the patient doesn't have an active malignancy somewhere. Age-appropriate [00:08:45] screening is always recommended in membranous nephropathy .

And always make sure there are no meds that could be kidney toxic that they're on. And lastly, make sure there's no hepatitis infection because before you start any of these immunosuppressions we'll be talking about, you wanna know if they're hep B [00:09:00] positive or hep C positive or quant positive because, quite frankly, there might be complications of your treatment if you don't check.

Koyal Jain: And to go back to our 50-year-old gentleman, there's no patient identifiers. I've changed a few things around just to make sure this is anonymous. But this patient ended up having a [00:09:15] malignancy, the malignancy got treated, and guess what?

The proteinuria came down.

Kenar Jhaveri: Even if PLA2R are positive?

Koyal Jain: Even though they were PLA2R positive. And so another thing to keep in mind, that PLA2R, although it's associated mostly with primary membranous, there are some [00:09:30] other conditions, especially hepatitis, where it's been seen to be positive. You've seen it in malignancy as well.

But we've not really seen it as much in the lupus population. So, that brings me to the point, how do we treat these patients who have membranous nephropathy? And the way I teach [00:09:45] my fellows is I'm a person who has to divide things into buckets or chunk information, because otherwise there's too much information to keep track of, and then you'll forget something, right?

The way I chunk things is, one, figuring out what the cause is, and I think you've [00:10:00] already alluded to that, Kenar, so I'm not gonna go into that in detail. But definitely do the screenings for the cancers, the infectious stuff, and syphilis, right? Don't forget syphilis is something that you need to screen for.

And then there's the conservative bucket, where I'm treating them with non-immunosuppressive [00:10:15] stuff, and then there's the immunosuppressive bucket, right? So the question in front of me whenever I see this patient, let's say this patient did not have a malignancy, right? Let's say I've ruled everything else out , and they have PLA2R positive.

Now almost everybody, or everybody really, gets [00:10:30] conservative treatment from me, but which ones need immunosuppression? I'm thinking about what their kidney function is doing . Is it declining? How high is the proteinuria? There was a study which divided patients into four grams, six grams , eight grams, and what they [00:10:45] realized is anybody who had greater than eight grams of proteinuria actually had a higher chance of decline in kidney function.

So those are probably the patients that you want to treat earlier with immunosuppression rather than later . But less than four grams, you have a lot more time with [00:11:00] conservative treatment. Do you agree with that?

Kenar Jhaveri: No, I don't. I'm not a big proteinuria follower. I'm more of a PLA2R antibody type. Historically, that was usually what we used. But if I have a person with eight grams of protein, but their PLA2R titers are fifty, [00:11:15] and then three months later they're twenty-five, and then they're less than ten, I'm not treating that patient, even if it's eight grams of protein, because they're immunologically getting better. But if their PLA2R antibody titer is over one-fifty and they only have four [00:11:30] grams of protein, that's a high-risk patient. I'm treating that patient regardless of their proteinuria.

So for me, the immunologic titer is far more important now than just proteinuria. And the other reason I bring that up is because the immunological remission happens way [00:11:45] before the proteinuria remission.

So even if I gave this patient, say, Cytoxan or Rituxan, their PLA2R comes down within a month, but the proteinuria might lag behind. The same way, before treatment, if they have eight grams of protein, but their PLA2R [00:12:00] is downtrending, I just wait and give them conservative management rather than aggressive treatment.

Koyal Jain: I do a combination. I haven't really talked yet about PLA2R. This is practical, right? Nobody really knows. I would say that if somebody has, let's say, a PLA2R which is modest, and [00:12:15] it's not even too high, but let's say they had ten grams of proteinuria, and let's say this is primary membranous. There is no way for me to know that three or six months down the line, this patient's PLA2R is gonna come down, right? And I'll be very honest here. I would still use [00:12:30] the proteinuria criteria because their risk is so high . And nowadays, with the newer medications like rituximab, I can't say there's no risk, but it's well-tolerated, so I might go ahead and treat them. So I would say yes, although I use both, oftentimes if the proteinuria [00:12:45] is too high, and even if the PLA2R is not too high, I would still treat them because I don't know what the PLA2R is gonna do in a few months.

Kenar Jhaveri: So I think we can use the Koyal-Kennar criteria. I just made that up. Maybe if we have two of the three. So if you have a GFR that's [00:13:00] declining at any point, if you have over eight grams of protein, like you said, or full-blown nephrotic syndrome with end organ damage, perhaps like a PE or something, and the PLA2R is over one fifty and are not declining. So maybe two out of those three [00:13:15] we would treat. And that's what the guidelines recommend anyway. See, we just came up with the guidelines just by talking to each other, and we hadn't even known that it was a guideline.

So if the GFR is not declining, if proteinuria is less than four, and the PLA2R titers are less than fifty or they're [00:13:30] declining, I wouldn't bother treating, right?

Koyal Jain: No. Okay, I wanna correct that this is my pet peeve. It's not that we don't treat, we just treat them with non-immunosuppressives.

Kenar Jhaveri: Yeah. The non-immunologic way. The old school nephrology way, right? You treat

conservatively first and then treat [00:13:45] the real disease. But what about in between? If

they have four to eight grams of protein, the PLA2R is around 90 . That's the one that can be confusing. I just watch initially and then see where things go. Or in [00:14:00] some cases , I might just treat because rituximab is so easy.

Koyal Jain: Okay. I think there's a textbook answer for both, which is that you can watch them for three months, six months, and then see. I would say personally I have treated many of them because a lot of times they present [00:14:15] with a quality of life issue, so I also want to provide them with the quality of life they deserve.

I don't know what's gonna happen in three or six months. But if it's less than four grams, for sure I'm not doing that . But the middle criteria I might err on the side of treatment depending on the quality of life and the other numbers .

Kenar Jhaveri: Fair enough. [00:14:30] So what is your conservative management?

Koyal Jain: Okay. This is like the conservative management for almost all nephrotic syndromes, right?

So we can just say this again and again. But it's really like the low sodium diet, especially if you have edema. Also cuts down the proteinuria, RAAS inhibition, hyperlipidemia [00:14:45] treatment, especially with the statin. The only thing I would keep in mind is what type of statin you use.

If you're using a CNI, you don't want the interaction there. Anticoagulation, if Albumin is too low in the blood, less than two, two and a half, depending on what you're reading as the guideline. SGLT2 [00:15:00] inhibitors, I would say that unless I'm actively giving them lots of immunosuppression, and I'm worried about an infection, UTI or fungal infection risk, I might end up starting that as well.

What else am I missing? Anticoagulation we mentioned with the albumin and [00:15:15] diuretics, if they have a lot of edema and quality of life issues again.

Kenar Jhaveri: Okay, that's fair. The anticoagulation becomes a little bit challenging, because most of us prefer using apixaban as opposed to Coumadin or warfarin. But the data is most robust probably [00:15:30] for warfarin, but I know it's much easier to use apixaban, and there's some observational data that it's relatively okay and safe.

And I usually stop it once the nephrotic syndrome has resolved. So the albumin starts going up, classically above two point five, two point eight, and I usually [00:15:45] stop the immunosuppression. Unless they had a PE,

then it's a different story.

Let's get to the crux of the therapy . So say your patient had ruled out cancer.

They truly were PLA2R positive membranous. The PLA2R titers are rising. Proteinuria is eight grams, and they do [00:16:00] have full-blown nephrotic syndrome. So besides your CKD toolkit that you talked about, what from your immunosuppressive toolkits would you pick, and why?

Koyal Jain: There's really three big buckets, right? One is the CNI bucket, one is the Ritux bucket, and one is the Ponticelli [00:16:15] cytokines, steroids alternating bucket. And I think we have the best data with the cyclophosphamide in terms of complete remission and maintaining that complete remission without relapses with the Ponticelli protocol, with the cyclophosphamide and steroids.

Now, [00:16:30] practically I've had fewer patients tolerate it as well. Because they go on steroids, they get off steroids, so you have to modify the steroid doses and how they come off of steroids in those alternate months. I will say that Ritux is so easy to get and so well-tolerated that I've used more and more [00:16:45] rituximab unless somebody really cannot tolerate it. So in all honesty , although the data is probably the best with cyclophosphamide, and there was, I think, one trial, I think it was the ReCyclo trial, which did show that there was really no big difference between [00:17:00] rituximab and cyclophosphamide. Some other studies have shown cyclophosphamide to be a little bit better.

I end up using a lot of Rituximab.

Kenar Jhaveri: So just so that people are aware what Koyal quickly said about the Ponticelli regimen, this actually was a brilliant design by Dr. [00:17:15] Ponticelli, where he took six months of therapy. The first month, say, could be steroids. You give three days of pulse, and then you do point five mgs per kg oral, and you cold turkey stop the steroids month two and give Cytoxan oral.

And then you cold turkey stop the [00:17:30] Cytoxan and give steroids. What that does is really minimizes your total steroid burden. The white count goes down, white count goes up the next month. Goes down, goes up. It really balances a lot of side effects. It's just a brilliant idea. And the total amount of Cytoxan [00:17:45] dosing is also minimized.

And that's it, six months of treatment, and some people have even done three months. As they see response, they stop treatment. And cyclophosphamide can be replaced with chlorambucil. And since it's oral cyclophosphamide, you don't get so much toxicity in terms of [00:18:00] the bladder and side effects. And the long-term side effects of malignancy or even immediate side effects of causing malignancy were not shown in RE-CYCLO and STARMAN trial when they compared that to Rituximab and tacrolimus.

So all in all, [00:18:15] the data is the best in the alternating Cytoxan steroids. So, why do people not use it? Because they're lazy. Most nephrologists will not be able to sit down and talk to the patients and go over this rotation, and make sure they do it. Patients might be lazy. They're like, "Well, I don't want to do [00:18:30] this switching around.

It's too complicated. Really, that's the bottom line. I don't think people are really scared of the cytotoxic effects of it because people haven't used it enough. I think when I've used it, I've had no problems getting these patients in remission beautifully. That being said, we do have [00:18:45] other options. I also like rituximab, like you said, and the MENTOR trial really put it on the map, especially for long-term outcomes. Two-year outcomes of rituximab alone were great compared to tacrolimus in the MENTOR trial, right?

Koyal Jain: Yeah - [00:19:00] cyclosporine.

Kenar Jhaveri: Cyclosporine, yeah.

Koyal Jain: Ritux versus cyclosporine, and it was great. And so, I find that a lot more people have moved towards rituximab. The one thing that we've really not touched on is: how quickly do people go into remission. I have had so many this point, so many second or [00:19:15] third opinions sent our way because a patient hasn't gone into remission, but you really have to give them time.

There was a study where they saw patients went into remission at the 12, 14-month mark, right? It takes a while for some of these patients to go into remission. It doesn't mean that they'll go into remission right as you're giving the [00:19:30] treatment or within a couple of months of the treatment.

And I think we just have to be patient - to wait and see if they go into remission. And let's say if I do use rituximab. I will go ahead and give them the six-month dose of rituximab because I'm anticipating they're not gonna go into remission within six months of the first two doses of rituximab.

Kenar Jhaveri: [00:19:45] that's true. And, you know, tacrolimus works fine too.

Koyal Jain: Yeah?

Yeah.

Kenar Jhaveri: People level around like five to seven or even nine, and you can get a pretty immediate response. But if you come off the tacrolimus, their relapse rates are higher.

Koyal Jain: Yeah . CNIs, we've seen a lot more partial [00:20:00] response than complete responses for our patients. I will also say the time I've used CNIs a lot more is when I'm doing some workup, right? Like, when I don't wanna give them this full-blown rituximab and cyclophosphamide, and I'm waiting for [00:20:15] maybe a couple of things.

My suspicion that this is secondary is really, really low, and I really still think this is primary, and I want to treat them because their numbers are so bad. But at the same time, - I just don't have all the data back, right? So in that case, I might start a [00:20:30] little bit of CNIs. I don't know if that's treating me or treating the patient, but I do believe that I've seen decrease in proteinuria, not complete remission typically, but some decrease in proteinuria.

And often times I've then switched them over to rituximab or cyclophosphamide .

Kenar Jhaveri: The other thing you could [00:20:45] do is use a CNI as a bridge till the rituximab kicks in. Like you said, because sometimes rituximab in some patient kicks in at one month, sometimes at three months, so why not use tacro or cyclosporine as a bridge so that once [00:21:00] the rituximab is given, then you can start tapering off the tacrolimus. That works most of the time . If you look at the STARMAN trial, they did it the backwards way, right ? They gave it after the rituximab. Most of us do it before the rituximab. And the other thing is what you talked about, the [00:21:15] response rate. I think if I see a pLA2R downtrending after the rituximab, or if i see that proteinuria might take a little bit longer, then I usually just wait and not add additional medications because immunological remission is [00:21:30] happening. But if, I've given the six-month rituximab dose after the initial induction and the pLA2R is still not downtrending but the CD19 is undetectable, that means there's zero, [00:21:45] maybe it's time to move on to a different type of agent.

Perhaps I would switch to a calcineurin or maybe we try a modified Ponticelli or we might have to consider anti-plasma cell agent, which is more experimental at this point.

Koyal Jain: One board [00:22:00] question that I think you briefly mentioned, but I want to emphasize: your PLA2R levels, as we said, that goes up before a flare happens and goes down before you go into remission. So it's not just that it goes down before remission, it also starts rising before the next flare typically happens , [00:22:15] right?

Is it 100% rule? No, but its a pretty good indicator that there's a flare that's going to happen or are they going to go into remission. So with that in mind, let's wrap up and talk about the latest trial, which is Obi or obinutuzumab.

So there is a [00:22:30] Majesty trial that just finished, and we don't really have all the final results yet, but is sounds promising in terms of obinutuzumab compared with CNIs and possibly Obi might be the new thing that we use instead of rituximab with the more complete and deeper [00:22:45] B-cell depletion.

Kenar Jhaveri: That sounds fascinating, and welcomed in the field of membranous nephropathy because I think we have enough things for IgA nephropathy right now. We need other GNs. But, I think it's a high risk of progression patients.

You should really be thinking about the stable [00:23:00] GFR rituximab over cytotoxic therapy. But, if the creatinine continues to worsen, or if they have declining other complications, I think the power modified Ponticelli is the way to go with most of these patients. Follow your pLA2R levels before [00:23:15] the proteinuria remission. The calcineurin, especially tacrolimus, is not a bad option. You will see an immediate response, but it's not more long-term. You should be thinking about rituximab as the first-line therapy for membranous nephropathy if it's pLA2R [00:23:30] positive. And we didn't talk about the other antigen-positive membranous, but a lot of them are linked to the cause of that.

So if you find a cause, and it's NSAIDs, and that antigen is positive on the kidney biopsy, then stop the medication. For [00:23:45] NEL-1 membranous, some of it can be sort of autoimmune, and might respond to similar treatment as we talked about regarding pLA2R.

Koyal Jain: Yeah. And then the cool cases really are the lipoic acid that people are taking supplements [00:24:00] of and then develop an L1. But also remember, even in those cases, you have to make sure there's no malignancy because it can happen with malignancy. With that, let's wrap up this episode.

Kenar Jhaveri: Great! This is Kennar and Koyal signing off on BRB. See you guys

Laurel Damashek: [00:24:15] This has been GN in 10 from the International Society of Glomerular Disease. You can listen and subscribe wherever podcasts are found and tweet at us at ISGDtweets. Thank you for [00:24:30] joining us.

Koyal Jain: And I don't know, Kenar, why do I keep calling you Dr. Jhaveri?

Kenar Jhaveri: I don't know why you keep switching names,

Koyal Jain: I don't know. I don't

Kenar Jhaveri: like, you're like class switching, you know, from IgG1 to IgG4.

Koyal's done boasting about her episodes.

Koyal Jain: I did [00:24:45] say that you were the favorite host

Kenar Jhaveri: We, we can have the audience decide that one. So I think you're definitely my favorite co-host

Koyal Jain: Oh, that's sweet. Thank you so much. And so are you. So are you.