Understanding Nephrotic Syndrome and Treatment

What's up Ninja Nerds? In this video today we're going to be talking about nephrotic syndrome. It's one of the types of glomerulonephritis. It brings a lot of students a lot of fear and anxiety. I'm going to do my absolute best to make sure that at the end of this video you guys understand it. If you guys do like this video it makes sense, it really does help you, please support us. One of the best ways that you guys can do that is by hitting that like button. commenting down in the comment section and please also subscribe if you guys do want to follow along with me we got some great notes some great illustrations that our team has worked together to make just some beautiful notes and illustrations for you guys to follow along with me and really understand this topic so go down in the description box below and it'll take you to our website where you guys can follow along with me but let's start talking about nephrotic syndrome so Before we actually get into the, you know, the kind of the meat and potatoes of nephrotic syndrome, I want to go over the basic functions, the anatomy of the glomerular filtration barrier. It's really important that we understand this because once we build on those basics, we can kind of really understand the pathophysiology. So the first things first, as we talk about the glomerular filtration barrier, it's really just three layers. So I have it abbreviated, I'm going to abbreviate it as GFB, the glomerular filtration barrier, if you will. Now there's three different components of this barrier. The first one is going to be this red capillary here. So you know you have the glomerular capillaries, they're supposed to be what's called fenestrated. So which means that they're a little bit porous and they allow for things, particularly selective things, to be able to move from the plasma of the blood into this actual Bowman space. So that's the first kind of component of this barrier here is you have what's called, let's actually do this one here in black, this is called your fenestrated capillaries. All right, so these are porous and they are allowing particular things to leave. through here but we want it to be very very selective though alright so we have finished rated capillaries the second component is this blue structure here you see that one right there this is a really interestingly negatively charged kind of membrane, if you will, and it's really nicely sticking and adhering to the finish rate of capillaries, but it's highly negatively charged. You know what's really interesting? Proteins that run through our bloodstream, they're very negatively charged. So negative and negative charges should kind of repel each other. We know like and like charges repel one another. So it's really good at being able to block large proteins from exiting the blood and coming into this capsule space. So that'd be the second component of the barrier here, which is going to be the glomerular basement membrane. The glomerular basement membrane. Now again, with this one, you need to remember it's that negatively charged membrane. So that's what's really cool about that. So I'm gonna put this here, and like this thing here, negatively. charge just to remind you kind of that function. The third component of the glomerular filtration barrier is gonna be these like cells here. You see these like little cells? They're kind of like right next to the glomerular filtration, the glomerular basement membrane. These are called your podocytes. So this is the third and last component of this filtration barrier. This is going to be the podocytes. Now the podocytes are really cool and what happens with the podocytes is they have like these little like you can't see them but you see like there's little divots there. They're called their foot processes. And generally there's some spaces between them called filtration slits. And that's supposed to again allow for some degree of permeability across this filtration barrier. So the third component here is going to be the podocytes. And again, the real significant component of this is going to be what's called your filtration slits. Alright, now you're probably wondering, okay, we got a little bit of basics here for nephrotic syndrome, I get it. Why is this so important? Well, the glomerular filtration barrier is supposed to be very, very important in being able to regulate what leaves the blood and enters. into this space here, the Bowman space. We really only want certain things filtering out of the bloodstream and into the actual Bowman space. We only want certain things, things like sodium, things like water, things like electrolytes and nutrients. But you know what we don't really want running through here? What we don't want to be leaving is we want the glomerular filtration barrier to block the loss of red blood cells, white blood cells, and proteins. And that's the job of this glomerular filtration barrier. Now imagine for a second you develop a damage. To one of these three components of the glomerulofiltration barrier, are you going to be able to closely regulate what leaves the blood and enters into the bone and space? No. And so that's the important thing here, is that this whole membrane here, it's supposed to block the loss of red blood cells, white blood cells, and proteins. There's two diseases that are a part of what we call glomerulonephritis. One is called nephrotic syndrome. So one is called nephrotic syndrome, and that's what we're going to be discussing. Now nephrotic syndrome, really how it breaks down the glomerulofiltration barrier, if you will, is it really takes a hit to the podocytes. So what this son of a gun does is, is it really causes a lot of podocyte injury. So it causes a lot of podocyte injury. And so whenever you damage these podocytes, it's one of these actual particular components of the filtration barrier. And then look what happens. As a result of the podocytes that are actually being injured, you lose the capacity to control what things are leaving the blood and entering into the Bowman space. Now out of all of these three, and we're going to hit on it a little bit more, the true one that actually ends up becoming the most affected is proteins. And you're going to see a massive, massive amount of protein loss. So protein loss is going to be the heavy, heavy cause here that you're going to see in nephrotic syndrome. So the big, big bare bones things to understand for the glomerular filtration barrier is that, again, it's made with these three layers. But which one of the layers is damaged in nephrotic syndrome? It's the podocytes that are injured. They are supposed to be controlling what leaves the blood and enters into the bone and space, particularly red blood cells, proteins, white blood cells. But the most important one. is going to be proteins. And if you damage these podocytes, you're going to lose a lot of proteins. So that leads us into the next component here, which is nephrotic syndrome. So we know that nephrotic syndrome, the basic concept of this disease process, which is again, it's kind of an umbrella. So when we talk about glomerular diseases or glomerulonephritis, it's the inflammation of the glomerulus. And this can present in a couple of different ways. One of the ways that glomerulonephritis can present is in the nephrotic syndrome. Another way it can present is in nephrotic syndrome, which we'll talk about in another video. But nephrotic syndrome, so what we know is, we know right away that there's some type of podocyte injury, if you will. And whenever you have this podocyte injury, what it's really going to be doing is... Is it's going to cause these poor little cute podocytes to become damaged in some particular way. And whenever you damage these podocytes, you technically, what you do is you kind of efface. So you see these like little foot processes? You actually efface them. So you get rid of them. And then you kind of like make them flat and they lose the ability to really control permeability. And so what happens is, is you end up with what's called podocyte effacement. So you end up with some type of podocyte effacement. And the problem with this is, we already kind of mentioned it, is this is going to lead to a heavy, heavy degree of protein loss. So what you're going to see is, as a result of this podocyte effacement, is you're going to see heavy, heavy degrees of protein. is being lost across the actual glomerular filtration barrier. So here, let's actually represent these as proteins. So here's all the proteins that I'm gonna be losing here across the Bowman space. And they're gonna end up draining all up into the urine. So what you're gonna notice as a result of this podocyte effacement is you're going to notice what's called heavy, heavy proteinuria. So we notice something called proteinuria. And we have to be very, very specific to the degree of proteinuria. I keep saying heavy. What I really mean is, is that the amount of protein that's truly being lost is very significant. We say it has to be greater than or equal to 3.5 grams of protein is being lost. in the urine per day. So that's what I really want you to take away from this, is it's 3.5 grams or more being lost per day in the urine. That's one of the hallmark signs of nephrotic syndrome. Secondary to podocyte injury and effacement, one of the components of the, again, glomerular filtration barrier. Now, When you lose protein in the urine, what happens is you have less protein that remains within the blood, right? So we know that here's the proteins we're going to kind of represent here. They're supposed to be circulating through the bloodstream. They go through the glomerulus. Generally, it's not supposed to be getting filtered off, my friends, right? So what should happen is that when we leave, when the blood leaves this, so this is what's called your afferent arteriole, and this is your efferent arteriole. When blood comes out here, what should be the albumin level in normal people? It shouldn't be very, very low. But in these patients who have nephrotic sin, When the blood leaves, guess what happens to their albumin levels in the blood? It drops. And so does other proteins. So let's talk about that. So we end up with what's called hypoalbuminemia, which is low albumin within the blood. This can cause a lot of problems, but what are some of those problems? So one thing is that we're going to have less albumin. in the blood. We can call that hypoalbuminemia. So, albumin within the blood. Now, why is that a problem and what can that lead to? Well, albumin is a really interesting type of protein. It helps to regulate what's called osmotic. or oncotic pressure if you will. So let's say that here I show these albumin proteins here that's in the bloodstream. Normally what it's supposed to do is, there's water that sits in the cells and in the spaces and they should get kind of sucked in or drawn into that actual space there. But as you lose albumin, you lose this oncotic pressure and you lose the ability to draw water into the cells. Now, as a result, because of decreasing the osmotic pressure, what's the end result here? As you decrease the osmotic pressure or the oncotic pressure, they're both kind of similar terms, semantics. really, it leads to a lot of fluid staying in these tissue spaces. And what will that look like to the patient when you look at them, you know, in person, it's going to give them a lot of edema. So a lot of fluid sits in these spaces and the ways that these present patients will present is they present with what's called edema. Now the question arises, what does edema look like? It can look like a lot of peripheral edema on their legs. They could have pulmonary edema fluid in their lungs. They could have fluid in their belly, ascites. Or sometimes it can even sit around their eyes, periorbital edema. So a lot of different problems here. That's one thing, is they can definitely have a lot of edema. What's another problem though? I'm going to write it here, but I'm going to explain it up here. Another issue with low albumin... is it increases your lipids. So it increases your lipids. You're like, wait, what the heck? How the heck does it increase my lipids? What you talking about, Willis? When there's low albumin, albumin is made by the liver, right? And so your liver is like a little albumin sensor, if you will. And it senses the albumin levels within the blood. And it says, oh, shoot, man, albumin levels below. Well, I'm going to have to compensate for this. And I'm going to start trying to pump up my production of albumin. So it tries to go and synthesize albumin as a result. That's what it's trying to do. You know what ends up happening? It also ends up making some other proteins that are similar. And these are called lipoproteins. So we call these things like VLDL and LDL. And you know what these sons of guns do? These sons of guns increase your triglycerides. They increase your cholesterol. and you know what ends up happening? These things get into the bloodstream so you have higher amounts of these. These things move right into your bloodstream right? So now look, look at this. You got increasing levels of these lipoproteins. These lipoproteins will then circulate through your bloodstream. They'll go to the kidneys. And when they go to the kidneys, they'll filter out. Look, you're going to filter out a bunch of different lipids. And some of these lipids will end up into the urine. Some of them will actually passively move into these tubular cells. And tubular cells, just like other people, they don't like, you know, getting all fat. And so they decide to just die and shed off into the actual urine. And so then you get like some cells. That are filled with a bunch of fat. And you know what we call this? What do we call this when you have tons of lipids within the urine? Oh, it's not too crazy. It's lipiduria. So we can have what's called, I'll actually write this down here, you can have something called lipiduria and you can have another one here. So there's two terms that I want you guys to be familiar with. One is what's called lipiduria and the second one, which is the cells filled with all that fat, these are called fat fat, oval bodies. How original, right? Sometimes when you look at them under microscopy and you really get a good look at them, they kind of look like what they call a Maltese cross. But I think this is the big thing that you need to understand is that in response to low albumin, your liver starts cooking up a lot of other lipoproteins, which unfortunately has an adverse effect, increases your triglycerides, your cholesterol. You leak a lot of that into the urine. You know, another problem is what happens if you have high triglycerides and cholesterol in the blood? You can't get up with all kinds of problems man. So you'll see sometimes these patients Unfortunately as a result of all of these things in the blood So if these things are like just cooking up in the blood, you can see a lot of problems. Things like, you might have heard these terms like xanthomas, right? So these kind of like big things that form on tendons. You can get these fatty like plaques around the like the eyes, so xanthelasma. You know what the worst case scenario is? These things can plaque up the blood vessels. And you can end up with what's called atherosclerotic cardiovascular disease, right? This can look like peripheral artery disease. This can look like coronary artery disease or the worst case scenario, you can develop a cerebrovascular accident. So you see how having a lot of these nasty little molecules increase the risk of some lipid complications, but also leads to a lot of lipid loss within the urine. Okay, what else? Well, here's another thing you're like, oh geez. It causes Renin-angiotensin-aldosterone system activation. All right, man. This albumin does some stuff, doesn't it? It's kind of odd. So, yes, when you have less albumin, it causes edema, right? Because of this osmotic pressure. So we know how this will cause edema. But another thing is when you have less osmotic pressure, not only does it cause edema, but it decreases the amount of fluid that's in your vessels. Oh, what's that called? Your effective arterial blood volume drops. So you have a drop in the effective arterial blood volume When you have a drop in the effective arterial blood volume, isn't that just like the circulating volume going around the body? Yeah You know why that's a problem? The reason that's a problem is is that tells the kidneys that hey, there is a very low perfusion There's low circulating volume. Can you do me a favor and can you pump up? the renin angiotensin aldosterone system and it does and you know what the result of the renin angiotensin aldosterone system activation is is it causes your blood pressure to go up so what's the effects out of all of this well what we know is this can increase your blood pressure so let's actually make this nice and purdy here so we'll have it can increase your blood pressure you And it can activate sodium and water retention. So it can cause an increase in blood pressure. What's that whenever the blood pressure rises? Hypertension. So this is another common feature. And it can cause sodium and water. Retention. When you retain a lot of this, not only does that increase your blood pressure, but what happens if you retain a lot of sodium water? You get puffy. And they start developing features of edema. So they can get edema because of renin-angiotensin-aldosterone activation. and because of low osmotic pressure. Son of a gun. So these guys just can't take a break, right? So we know now that they're losing tons of protein. The biggest one is albumin. And we see all the negative consequences of that. But there's other proteins that can be lost. Another protein that can be lost, and it's really important to differentiate this between nephrotic syndrome, is it's called anti, I'm going to abbreviate it, antithrombin 3. So if you guys remember from our hemostasis lecture, antithrombin 3 is an anticoagulant. What it's supposed to do is, is it should naturally, you know, there's molecules called factors 10. and another one called thrombin. And these are supposed to, what they want to do is, these molecules want to go and stimulate their procoagulants. They want to stimulate a clot. That is what they're designed for. to do they want to stimulate a clot to form all right that's their goal is to increase clot formation well you know antithrombin 3 is supposed to do antithrombin 3 is like on daddy you ain't gonna do that I'm going to inhibit you from being able to function and so antithrombin 3 naturally is supposed to inhibit these but if you have less antithrombin 3 are you gonna be able to inhibit these proteins no and so what happens is you aren't able to do this particular function because of a decrease in this molecule. And then these things go haywire, and they increase your clot formation. What does that look like? Well, you get clots, my friend. And usually this is venous clots. And so it can form in the leg. So watch out for those DVTs. They can break off, get stuck in the lungs, a PE. And a weird one is what's called a renal. vein Thrombosis, this is kind of rare, but if you think about this in the context of nephrotic syndrome, it is relatively common, okay? All right, what else we lose one other protein and that's these little dudes. These are supposed to be Plasma cells, but if you're losing more than your plasma cells are able to produce these are called immunoglobulins or antibodies Immunoglobulins Now you're jacking these things up. These are supposed to go and fight off bacteria You know the very specific bacteria that for some reason patients with nephrotic syndrome are super super susceptible to It's called streptococcus pneumonia And what happens is you have less of these antibodies. So are you able to bind up this bacteria, enhance opsonization, complement pathway activation? Nope. You lose this. Strep pneumonia starts going on the rise. And if it gets on the rise, guess who likes to plague and increase the mortality for these patients? Son of a gun. It loves to hit the lungs. And so you can end up with a nasty, nasty pneumonia. And so as you can see, the complications of... having less of these immunoglobulins is you're going to be at very high risk of infections. So you're going to have infection risk that's going to be a little bit higher than most people. And that's the problematic issue. And I think the big boards question that you can see for this is it streptococcus pneumonia and usually streptococcus pneumonia is the most common cause of community acquired pneumonia. So you want to watch out for that pneumonia in these patient populations. So, at this point we've talked about nephrotic syndrome, what it really looks like when you damage those podocytes. But the question that arises, what's causing the injury to the podocytes? Let's talk about that. All right, my friends, so now we have to talk about the reasons the podocytes are damaged or injured and we're losing all this protein. So the first one that I want to talk about is called minimal change disease. So before we even talk about that, there's three particular types of nephrotic syndromes that really are what we term primary meaning that we don't really know the reason why these are occurring they're what we call idiopathic there may be some genetics or autoimmune things but we just don't know then there's what's called the term secondary causes of nephrotic syndrome which you can see in every single one of these okay but just remember that the ones that we call primary nephrotic syndromes is minimal change memory nephropathy and focal segmental glomerulosclerosis you I'll explain that a little bit more as we go along. But first thing is minimal change disease. So a minimal change disease, it can be primary. We don't know the reason why it happens, okay? So when I say primary, primary for these three accounts for 70 to 80% of the nephrotic syndromes. That's insane. So most of the time, it's primary. But when I say primary, we don't know why it happens. So we'll use this term idiopathic, meaning we don't know. But there is secondary causes, meaning that we've seen some association of this disease with these particular things. And what they've seen is for the secondary causes, they've seen things like infections, like upper respiratory tract infections. and Hodgkin's lymphoma. The only other one is NSAID use. So you can also add that one in as well. So NSAIDs have also been kind of linked to this. Now, how exactly these things do this next step, we just don't know. And I always feel bad for that, but I don't have an answer. But what we know is, is that these particular things, whether it's idiopathic or it's secondary, what they do is they stimulate T cells, all right? And these specifically target these T cells to go to the kidney and release tons of these cytokines. And what these cytokines do is, is they go and they cause damage to the podocytes. And really all they do is they rip the foot processes off. So what you get is, you get what's called podocyte effacement, which we talked about. And that's really the interesting thing with this. And then as a result of the podocyte effacement, and What do you lose a lot of in the urine? You lose a ton of protein in the urine. How much? Just to test your knowledge. Greater than 3.5 grams per day. And you also can lose a lot of lipids in the urine. So you can get that lipiduria, right? Now, the big concept for this is, again, we're knowing that these cytokines, by some particular means, are injuring the podocytes. They're getting effaced. And these podocyte effacements are increasing. the protein loss, and then subsequently from a lot of albumin being lost, a lot of lipiduria. So you're getting podocyte effacement from increased cytokines. And here, we'll just kind of draw this here so that you see. you're damaging these podocytes. Now that's really the key thing. So when I say minimal change, think about a young child, all right? And it's usually either primary, idiopathic, we don't know, or secondary, something else has been associated with it. Infections, maybe even immunizations, Hodgkin's lymphoma, and NSAIDs. All right, that's enough said. Membranous nephropathy, again, can be primary, but thank goodness we have something to link with it. So in primary causes there's this weird antibody and it's called anti-PLA2 receptor antibody and it's for some reason loves one of the proteins in the podocytes. It loves one of those proteins. And it loves to attack it and efface the podocytes. If I were to say secondary causes, then you're thinking about things that have been associated to lead to antibody activation. And this is things like hepatitis B, hepatitis C, syphilis, and there's one other kind of weird one. There are these two weird medications. One is gold. and the other one is called penicillamine. But these are the weird things that for some reason have been associated with membranous nephropathy. Now, regardless of what that may be, what happens is, is you get some type of antibody. that is actually going to be in some way binding with one of these antigens or the antigens that are present here. And so you're going to either get like these immune complexes and what they do is they go in and they deposit here right into the what's called the sub epithelial layer all right and when they deposit in there look at this you get all these kind of like deposition here this could be the anti-pla2 antibodies or this could be all of the other antibodies from hepatitis syphilis etc but you get a lot of antibody deposition so what's the result of this is you get what's called sub epithelial Sub-epithelial immune complex deposition. And when these suckers deposit into this area, they trigger an inflammatory reaction. And what they do is, this subepithelial immune complex, they activate complement proteins, my friend. So you're going to activate these complements. You guys remember those? The C3, C4, all those things that come in there and really trigger a lot of inflammation. So what you're going to do is, is you're going to stimulate the complement system. And when the complement system gets in there, it's gonna jack everything up. And then as a result, you're gonna get podocyte effacement. But you also get one more thing. When that complement system gets in there and really starts revving up a lot of activity and getting super inflamed, not only do you get a lot of podocyte effacement, But you also start causing some other problems, which is the glomerular basement membrane starts kind of having a reactionary thickening. So the GBM will start thickening. It's going to get thick. And when you get this GBM thickening, it does something kind of like weird, where when you actually kind of like zoom in, and we'll talk about it a little bit later, here's your glomerular basement membrane, all right? And then what happens is you have your kind of podocyte. that would be on this side here. So we'll kind of give them a little bit of space here. Here's your podocytes. Look, their foot process is gone. All jacked up. But what happens is right in here is going to be your immune complexes. All these things that we're depositing. You know what the GBM does when it thickens? It does something weird where it kind of like thickens outwards. And when it thickens outwards It gives this weird type of appearance that we'll talk about later. And it's called a spike and dome pattern. So we call it a spike and dome type of pattern. And that's really, really interesting that you get with this GBM thickening, okay? All right. So that's what we get for membranous nephropathy. So when I say minimal change disease, you think child, idiopathic. Secondary, you think like infections, maybe NSAIDs, Hodgkin's lymphoma. Membranous nephropathy, primary, it's one weird antibody. And if I were to say the... primary if I put the primary here what would that primary antibody be it would be anti-pla2 receptor antibody this is the one that's the primary cause if it's not this antibody then you have to remember it's an immune complex where antibodies bound to one of these things and then deposited into that space. Okay? All right. Let's come on to the next one. The next one here is focal segmental glomerulosclerosis. Now, with this one, The big thing to remember here is this can also be primary. Believe it or not, it tends to be, out of all of these, like the primary causes, this one is the most common to be the primary type. So if we talked about particularly all of these different types of diseases for... nephrotic syndrome this is one of those that the primary causes is the most common there really isn't many secondary causes but we'll talk about those rare situations so primary I want you to associate with idiopathic right we don't know why something genetic we just don't know secondary there has been a couple things that have been linked to this HIV heroin use, dang, and also sickle cell disease. There also has been an association with like obesity, but I think these are the ones that you're more likely to see on the exam. Now, what happens with this one is again, we don't know. I don't have an answer as to why these things happen, but something occurs where you activate a lot of like sclerosis and hyaluronosis of of parts of the glomerulus. That's why we call it focal and segmental. It's not the entire thing. So imagine like right here in this area, I'm gonna have a lot of sclerosis right here in this particular area. So there's gonna be a lot of sclerosis and then we'll use like a different color here. Maybe we'll do like a little bit of pink or something. And this will represent the hyaluronosis. So you're gonna get kind of like a hyaluronosis and sclerosis of parts of the glomerulus. Weird, right? We don't know why, but it just happens. So you can get what's called hyaluronosis and sclerosis of the glomerulus. The glomerulofiltration barrier, if you will. And what this does is this causes podocyte. So you're noticing a trend between these three primary types of disorders is that no matter what it may be, you're getting some degree of podocyte effacement. And this one is going to be due to a lot of hyaluronosis, and sclerosis of that glomerular filtration barrier. Now, that's the big thing to remember for these. Okay? Now, here's the next thing with this particular disease. With focal segmental glomerular sclerosis, and membranous nephropathy, because you can cause potentially over time a lot of damage to these kidneys, it's important to remember that in situations where these patients have focal segmental glomerulosclerosis and membranous nephropathy, so in diseases such as membranous nephropathy and focal segmental glomerulosclerosis, these can really plague the kidneys. They can really do a lot of damage if they're not treated. And what can happen is as you continue to plague these kidneys and injure them and injure them and cause inflammation and fibrosis, you can literally progress these kidneys into something called chronic kidney disease. But these are really the only two that have that higher risk of end-stage renal disease or chronic kidney disease. Minimal change disease, not so much. All right, we go on to the next one. Diabetic nephropathy. So at this point, we're now talking about only secondary causes of nephrotic syndrome. So what are the reasons the podocytes are being injured or damaged in some way, shape, or form? For the primaries, it was minimal change, membranous nephropathy, focal segmental. If it's not primary, which is usually the most common cause for those, meaning it's idiopathic and we don't know why, then there's some random secondary ones that we talked about. But for these, it's only secondary causes. So it's some systemic disease that causes nephrotic syndrome. diabetes or amyloidosis. So obviously in diabetic nephropathy the hint to knowing this one is you got a patient with diabetes and what's the problem with diabetes what does it really do well you got that high glucose right and what that glucose does is it causes if you guys remember that non enzymatic glycation of the efferent arterial whoo shoot so you get what's called efferent arterial hyaline arteriolo oh my gosh so many words sclerosis and what that does is it makes it super impossible for blood to leave the glomerulus and then the glomerular blood pressure is like crazy high and you hyper filtrate we already talked about this before right but what happens is your intra glomerular blood pressure rises Narylofiltration rate would rise and so you're gonna have to compensate and protect the kidneys from that high pressure my friends. And so what you do is you cause GBM thickening and you cause sclerosis in a nodular pattern. And what this does is when you thicken up that GBM, it causes the podocytes, the foot processes to be farther away from one another. So it causes the podocyte foot processes to stretch out. the same way of causing podocyte dysfunction. And if you do that, you're going to get the heavy proteinuria because you're causing podocyte dysfunction. So in this particular situation, what we know is the increase in efferent arterial high arteriosclerosis reduces blood flow out of the glomerulus, increases the blood pressure, increases the GFR, thickens the glomerular base membrane, causes sclerosis, and then effaces those foot processes. And that is how we end up with this heavy, heavy degree of protein loss. The other thing is that with this over time, the sclerosis and nodules, you can lead to what? Chronic kidney disease. My friends, what is the most common cause of chronic kidney disease? Diabetes. And this is because it's going to damage and cause tons and tons of sclerosis to the kidneys that they... will progress to chronic kidney disease. If I were to ask you what's the most common cause of chronic kidney disease, you should say diabetic nephropathy. If I were to say what's the most common cause of nephrotic syndrome, you should say diabetic nephropathy. And that is the important thing. thing to remember for this one. The last one here is just kind of a weird one. We got to talk about it unfortunately because it's a part of the nephrotic syndromes, but it's amyloidosis. And this deserves a quick discussion as to the two types of amyloidosis. So there's what's called AL. So AL, amyloidosis, that means light chain amyloid proteins. You know there's a disease where you produce lots of these light chains unfortunately? Multiple myeloma. So in patients who have multiple myeloma, they're at high risk of injury to their kidneys. We know that that's one of the features, right? Multiple myeloma. If you guys remember like that crab mnemonic, the hypercalcemia, the renal failure, the anemia. the bone pain, that's one very particular significant feature. The other one is what's called secondary amyloidosis, which means there's something that's causing chronic inflammation which is leading to a lot of these amyloid proteins to be produced. You know what that disease is called? It's really any disease that has chronic inflammation. What's a big one? RA. Rheumatoid arthritis causes a great degree of inflammation. But the difference is in really just the protein kind of like structure and composition. But either way, the same kind of thing exists between these, which is your body is, regardless of what the structure of them is, your body is producing an increased amount of abnormal proteins. And so, That's the whole point with this one is you're getting a lot of abnormal proteins, my friends. And when you get a lot of these abnormal proteins, guess where they decide to go? In the same situation here, my friends, they like to go here and they like to deposit into the glomerular filtration barrier. And when they deposit, what they do is they cause a lot of inflammation. And guess what they do? They do the same thing that this diabetes does. They cause GBM thickening. So they thicken up that glomerular basement membrane, so they cause GBM thickening, and then they also cause a lot of inflammation and then sclerosis, so they cause a lot of sclerosis of the glomerulus as well, somewhat in a nodular pattern. But if that happens, what's the end result that we saw within diabetes? Same kind of thing. You're getting the foot process effacement. I'm sorry. You're actually stretching out the podocyte foot processes. I apologize. Which is the same thing because you're causing podocyte dysfunction, leading to the loss of the good filtration barrier and proteins to get lost. loss. The other thing is with the sclerosis, what can you also progress this thing to? Chronic kidney disease. So you're noticing a trend with all of these nephrotic syndromes. The only one that really won't really progress to renal failure is which one? Minimal change disease. The ones that can progress to renal failure that are primary is membranous nephropathy and focal segmental glomerulosclerosis. The ones that can progress to chronic renal failure is going to be diabetic nephropathy and amyloid nephropathy. We've gotten the causes, minimal change, membranous nephropathy, focal segmental, diabetes, and amyloid. The question then comes, because A lot of this, this is a lot of information. How am I supposed to know which one it is off a patient who comes in with some vague symptoms like some edema, right? Or maybe they have high lipids, or maybe they have hypercoagulable states, or maybe they have increased risk of infections. They got a lipid in their urine, they got a protein in their urine. How am I supposed to know? Let's talk about that. All right, my friends, so we have a patient that we think may have nephrotic syndrome. So sometimes looking at the physical exam features that we talked about, kind of the effects of nephrotic syndrome, really was looking for any features of edema, right? So periorbital edema, pitting lower extremity edema, pulmonary edema, ascites, that could be one thing. Or if they come in with a history of recurrent DVTs, PEs, renal vein thromboses. If they have complications of hyperlipidemia, xanthoma, xanthelasma, cardiovascular events. Or if they come in with increased risk of infections, like particularly streptococcus pneumonia. Now, with this being said, this is very vague, right? So oftentimes what ends up happening is if we have a patient who has like some degree of edema. We may get a urinalysis and microscopy. And the reason why this is kind of helpful is because this leads us into the next topic that we'll talk about in another video called nephritic syndrome. But I want to introduce it. I want you guys to be able to compare, contrast, differentiate these two. It's very important for your exams. So a urinalysis and microscopy is really good. It just doesn't quantify the protein loss as much, which is really, really important. But it gives you an idea, hey, there's a heavy amount of protein, there's some other weird stuff in here too. This is where it's really good at being able to differentiate between nephrotic and nephritic syndrome. So the basic, basic thing for nephritic syndrome is it's inflammation of the glomerulus causing glomerular basement membrane damage. Whereas nephrotic syndrome was inflammation of the glomerulus causing podocyte damage. Alright, both of them either way lead to loss of particular things into the urine. Nephrotic syndrome causes heavy proteinuria and lipiduria. Nephritic syndrome leads to everything being lost. Red blood cells, white blood cells. cells and protein. Would I be able to differentiate that off of a urinalysis with microscopy? Absolutely I would. So when I go look at nephrotic syndrome and I get a urinalysis, one thing I'm going to notice is I'm going to have two big things for nephrotic syndrome, two big things I notice in the urine. One is I'm going to have a massive, massive amount of protein and I'm going to have a lot of lipids. And if I look under microscopy, I'll also see those weird fat oval bodies, right? So I have a lot of what's called lipid urea. And if I look under the microscope, I can see those fat, oval, bodies, right, that we talked about in the lipid urea situation. The other thing is I'm going to have a lot of protein. Problem is, is I'm not going to be able to quantify this. So the dipstick kind of gives you like a plus one, plus two, plus three amounts of proteins. I'll have a lot of protein. So plus three, plus four protein urea. But it's not good at telling me the true amount that I need to know. Is it greater than or equal to 3.5 grams per day? I won't be able to get it off just a basic urinalysis. All right. So that's not crazy helpful, but it's at least something. Here's another thing. Nephritic syndrome, I told you. So again, this is podocyte damage. Podocyte dysfunction, if you will. Whereas in nephritic syndrome, it's glomerular basement membrane dysfunction is the basic pathophysiology. They both lead to heavy leakage. Now, the difference between this one is a little bit... different. So we're going to have protein, but it's not going to be as much. I'm only going to give it one arrow. We're going to have a lot of red blood cells and we're going to have a lot of like white blood cells. Huh. So what will I have? here I'll have some protein but it won't be as significant of the protein maybe this is like plus one plus two it's like plus three plus four still not great but it's okay but here's what's the big difference between these I'm gonna have hematuria and when I look at this red blood like the actual blood under the microscope I noticed something called red blood cell cas and that's usually a buzzword term for nephritic syndrome the other thing is I'll have what's called pyuria which is white blood cells, but sometimes people would be confused and they'd be like, oh, white blood cells, doesn't that mean there's an infection? This is what we call sterile pyuria. So it means that there's actually no evidence of infection, there's just a lot of white blood cells that leaked across the blood into the actual Bowman space. So that's kind of the basic differences. It's not enough, but it at least gives you kind of a basic beginning. I could at least tell off the urinalysis with microscopy which one's likely nephrotic, which one's likely nephrotic. But it's not stone cold kind of definitive. So then what I would do is I would do what's called a 24-hour urine protein or what we call a urine-albumin-creatinine ratio. So this you have to collect urine over a 24-hour period. That sounds very tedious, very annoying, probably not the most desirable thing to do. This one is what we call a spot. Urine analysis. We do it one time. People like that a lot more. And so they both are pretty good at giving you the amount of protein that you're losing in your urine over a 24-hour period. That's really helpful because I know in nephrotic syndrome, which is podocyte dysfunction, I'm going to have a lot of protein. But how much protein? How much do you have to have to truly be considered? Because you're going to get proteinuria here. There's still protein loss. But what is the big difference here? So I'm going to have protein loss in both of these. This one I already told you will be crazy high. This one will just be a little bit high. But what's the true number over a 24 hour period that we need to have? This happens. to be greater than 3.5 grams per 24 hour period and this has to be less than 3.5 grams per 24 hour period that is the big difference and that will set this apart between the two. So if you have heavy proteinuria with lipiduria, no hematuria and no sterile pyuria, it's more likely to suggest nephrotic syndrome. If you have hematuria, pyuria, and sub-nephrotic range proteinuria, less than 3.5 grams per day, it's more likely to be suggestive of nephritic syndrome because they both can have edema, which we'll talk about. They both can have hypertension, which we'll talk about, and they both can lead to renal failure, which we'll talk about. It's really this that helps you. Another thing that can be somewhat helpful in differentiating nephrotic versus nephrotic syndrome is in nephrotic you have a heavy amount of protein loss. But I was very specific. What was the most significant protein that was lost? There was a lot of albumin. There was a lot of albumin loss. And what did we say we would be able to determine off of the albumin in the bloodstream? Well, I told you that because this disease, there's podocyte dysfunction, it causes a lot of, here's our blue color here. a lot of albumin to get lost. So there's going to be a ton of albumin in the urine. What happens to the albumin that leaves the glomerular capillaries and goes into the efferent arteriole and into your circulation? What is it going to be here? It's going to be very low. So if we were to check the serum albumin levels, their albumin within the blood would be very low. And so they would have very low albumin levels within the blood. And we also can kind of make a little connection here that we said that when the albumin levels in the blood are low, what did that do to the liver? Stimulated the liver to pump what out into the bloodstream? Lots of lipids. Unfortunately, as the result of trying to make more albumin, right? And so if I were to test the blood, what would I find a lot of in the blood as a result of the heavy albumin loss? I would find a lot of... VLDLs, I would find a lot of LDLs, and maybe I would even find a lot of like high triglycerides as a result here. So you're going to notice that these patients will have features of hyperlipidemia on their lipid panel. Okay. And this again adds to the definitive shot of saying, oh, it's nephrotic syndrome. So if I've done all of these, I should be able to get to the point where I say, I know it's nephrotic syndrome causing some type of podocyte dysfunction, leading to heavy proteinuria and lipiduria. Then we got to get to the next step. Which one is it? Which is the cause of the nephrotic syndrome? Is it minimal change? Membranous nephropathy? Focusegmental? Diabetes? Amyloid? Zach, I don't know what to do. I got you. Let's go. Now we move into the next step here, which is we don't know which one it is. Is it minimal change? Is it membranous? Is it focusegmental? Is it diabetic? Is it amyloid? How am I supposed to figure this out? Remember I told you that out of all of those causes, it's likely going to be, again, primary causes as one of those big things. for minimal change or for membranous nephropathy or for focal segmental glomerulosclerosis. On the rare occasion for those three diseases, there could be secondary causes that we said have been associated with it. Those are things to think about and you could test for those things, right? Because right now we've already just gotten to the point, I know it's nephrotic syndrome, I just don't know which one it is. Look for specific hints. that may be suggestive. So for minimal change disease, I already said look for like a young child. So I think that's one of the big things to think about is a very young child because it's more common. It's one of the most common nephrotic syndromes in children. So right when you see that with nephrotic syndrome features, you want to think about minimal change disease. That's one way that they'll try to get you. The second one is we said that it could be associated in some way, shape, or form with Secondary causes such as what? Infections. It could also be due to Hodgkin's lymphoma or it could be seen in association with insets. So look for that. Look for Hodgkin's lymphoma in the vignette in a child which would be really sad. Look for insets in the vignette with a little child or look for some type of infection or even sometimes recent immunization for a child. Okay, but out of all of these ones, this is probably going to be the one that when you just bings up off the exam It really will help you to make that differentiation. Okay Now these are the secondary ones. It doesn't account for the primary one, which is we don't know why it happens, right? So that's why sometimes these three can be difficult to diagnose because if it is primary these things won't come up as very helpful For membranous nephropathy, what you really want to look for in the question stem is someone who is Caucasian, right? And this is usually an adult. So it's some type of Caucasian adult. And this is usually the epidemiological range where you can see this one. The other things that you want to watch out for is those infections. So you can test them for things like HIV, right? You can test them for things like hepatitis. You can test them for things like syphilis. I apologize. This one is specifically hepatitis B virus, hepatitis C virus. You can test for that. You can do the RPR, right? Testing for syphilis. If you believe that that could be a potential cause and then look for any medications in their history. So look for those particular medications that I told you, which was gold or penicillamine. So look for gold or some type of penicillamine. Now, this is for the secondary causes, right? I told you that there is one particular primary thing that we can test for, and I'll talk about it down here in a little bit, but it was that anti-PLA2 receptor antibody. You can test for that, but that's not a secondary cause, that's a primary cause. So again, that would be the big thing that would kind of ping off here is maybe this or potentially some of these for the focal segmental glomerulosclerosis you want to look for some type of african-american horse Hispanic male Hispanic adult These are usually the big things for this. So look for some type of African American or Hispanic adult. So again, what you're already noticing is that this could be one way of helping you to kind of stratify and differentiate is the child versus the adult. It'll automatically kind of like point to these two if it's adult. It'll kind of like point to this one if it's a child. So look for that. The other thing is we did say that this could be associated with HIV. So you go to HIV. you can do HIV testing and this can also be associated with heroin use. So looking for that potentially in their history as well as things like sickle cell and looking for obesity as another factor. Now these ones I think are probably going to be the easiest secondary cause. And I, again, I stress this. What's the most common cause of chronic kidney disease? Diabetes. What's the most common cause of nephrotic syndrome? It's diabetes. So diabetes is an easy one that you can obviously elucidate. Look for a history of diabetes, but ones what's the most common cause of nephrotic syndrome? Diabetes. what's one thing that I can do and I can test for to find if they have diabetes? A hemoglobin A1C, right? So that's usually gonna be the biggest diagnostic tool here is a hemoglobin A1C, like, you know, generally we like to see greater than 7% to really be a true effect on the actual kidneys. All right, but you know, generally by definition, it's anything like greater than 6.5%. But usually when you get to greater than seven, you start seeing a lot of kidney damage. All right, for amyloidosis. The big thing for this one is if you're really looking for amyloidosis, you want to consider things for multiple myeloma, right? Or a lot of this antibody deposition in other areas. So we can do two other tests if you're ever concerned for it. You can do what's called an S-PEP or a U-PEP. And that's usually very, very helpful for multiple myeloma. But if it's not completely clear, another one that you could do is you could do what's called a fat pad biopsy. And that's also very helpful. helpful for being able to identify amyloidosis. And that's why when you have a patient who has nephrotic syndrome and they have amyloidosis or diabetes it is very rare that you would ever get renal biopsies on these patients because diabetes is the likely cause and if they have a history of diabetes it's likely that and if they have a history of amyloidosis or you think it's amyloidosis I can kind of go away from doing a renal biopsy and do a fat pad biopsy okay but for completeness sake for the lecture you could consider doing a renal biopsy if there's an unclear cause of the nephrotic syndrome. In other words, it's a primary type, minimal change, membranous nephropathy, focal segmental, and it's idiopathic. I don't know why. There's no cues, there's no keys that really kind of buzz out and help me very much. That's where a renal biopsy would really kind of solidify this. But again, I need to make sure that you guys understand, for diabetic nephropathy and for amyloid nephropathy, it's relatively rare that we would obtain these particular studies. Even in minimal change disease, it's kind of rare that you would obtain it just because this is in children. Renal biopsies are relatively contraindicated in children less than 10 years of age. So it would also be something that you might not be getting. But if you did get the renal... biopsy, what they do is they take a chunk of tissue out and they take that tissue and they look at it under three different types of ways. One is they look at it in what's called light microscopy, electron microscopy, and immunofluorescence. All right, basic things for this one. Light microscopy gives you general details. There's some general basic look at the glomerulus. Electron microscopy zooms in on the podocytes. That's what I want you to remember. General look at the glomerulus zooms in on the podocytes. Immunofluorescence looks for antibodies or some type of immune complex that are deposited in the glomerulus and lights it up a beautiful fluorescent green. That's it. General change zooms under the podocytes, looks for antibody or immune complex deposition, and lights them up green. That's what this is helpful for. And already I can tell you which ones are beneficial. Minimal change is the beautiful name. It's a beautiful name because really there's only one thing that's happening with this. It's podocyte effacement. So if I'm effacing the podocytes, what would be, out of all of these, the test that would be very helpful? Electron microscopy. So the electron microscopy is going to be the best particular test here because what it's going to show me is the podocyte effacement. The light microscopy and immunofluorescence will be completely normal. That's why it's a very minimal change. But membranous nephropathy, I said that there was immune complexes. They were depositing. into this particular area here. So they were depositing all up in this area here, really causing a lot of problems. So if I were to do these, I could actually see something in each one. If I did light microscopy, I may see something. What would I see? Generally you see a lot of just thickening of the glomerular basement membrane. If I did electron microscopy, I zoom in on the podocytes. What would I see in the podocyte area? I would see effacement of the podocytes. But what else would I see? I'd see a lot of these immune complexes deposited in that subepithelial layer. and immunofluorescence, it's the one that's going to be the most helpful. Why? Because I'm gonna light this thing up beautifully green, showing that there is these antibodies that are depositing and kind of this nice granular fashion in that area. Okay, so this will show GBM thickening. This will show that spike in dome pattern with podocyte effacement from the subepithelial deposition. And this will show a nice granular green pattern. This one, for this one, if I did light microscopy, it'll give a general look. And what it will show is it'll show a lot of that hyaluronosis. and sclerosis. So to show a lot of hyaluronosis and sclerosis of segments and parts of the glomerulus. On electron microscopy It'll zoom in on the podocytes and show podocyte effacement. So for each one of the electron microscopies, what should you see? Podocyte effacement. Which one will only have immunofluorescent positive? Membranous nephropathy. Which one will only have hyaluronosis and sclerosis? Focal segmental glomerulosclerosis. And which one will have GBM thickening and a spike in dome pattern due to the immune complex deposition? Membranous nephropathy. That's it. So that's why these are relatively easy if you do a biopsy to identify. These ones you won't be doing it because it's really off their history and you can avoid biopsying these patients. But if you did. Really, you could get most of your information off of these because what you're going to notice from these patients is they're going to have a lot of that nodular sclerosis. We call this the Kimmel-Steele-Wilson nodules. That's going to be pretty obvious off their kind of light microscopy. So you can honestly just do like light microscopy for these patients and be able to notice those Kimmel-Steele-Wilson nodules. Same thing for amyloid nephropathy. You're going to be able to notice a lot of like that sclerosis. Of the actual glomerular filtration barrier and it can be nodular but here's the key thing They stain it. Hey, they they stain the actual the biopsy tissue And what you look for is this weird thing where the amyloid proteins when you stain them with what's called a Congo red stain They light up like an apple green color. So you go it's called apple green Bifrigen on a Congo red stain of this biopsy. All right So I know this is a lot, but I just want you to get the basic idea that we would only go to the renal biopsy, usually if it's a primary type of nephrotic syndrome. So minimal change, membranous nephropathy, focal segmental, where it's idiopathic. We don't know the cause. Rarely for amyloid and diabetic. Okay? With these, you can get a good amount of findings to truly differentiate which type it is. Now, that leads to the last step here, which is how do we treat nephrotic syndrome? Let's talk about it. All right, so we've come to the point where we've said, okay, it's nephrotic, it's not nephrotic. We figured out the cause. If it was minimal change. Focusegmental, Membranous Nephropathy, Diabetic, Amyloid. If we were really kind of not sure, we could do the biopsy if we need to, to really delineate it based upon electron microscopy, light microscopy, immunofluorescence. We got to the point where we go, I know the patient has nephrotic syndrome. It's easy to treat this because you're treating the complication and then you're treating the cause. And the complications are very straightforward. We should know this. Proteinuria, you're losing tons of protein. This is the only one when I want to mark the kind of mechanism just quickly because a lot of these are straightforward. and it makes your treatment, you know, remembering these very easy. This is the only one I want to go into a little bit more detail for. So for proteinuria, obviously kind of maybe controlling the diet. So not kind of restricting proteins, but really trying to just limit excessive amounts of protein. And then the other one is ACE inhibitors and ARBs, if their blood pressure tolerates. And believe it or not, these patients also have that hypertension from the renin-angio. angiotensin aldosterone system. So they will likely tolerate it. But I want to explain how this helps. Okay. So we know that in this patient who have nephrotic syndrome, their angiotensin 2 levels are usually high because of the RAS activation, right? So if you have high angiotensin 2, what that does is it basically causes efferent arterial vasoconstriction. So watch this. Look how narrow this sucker is going to be. There's like no blood. leaving that glomerulus. All right? And so because of this, one of the problems is that whenever you have high angiotensin 2, we said it increases the intraglomerular blood pressure, that increases the GFR, and this increases the protein loss. All right? So this is kind of like that downstream effect from high levels of angiotensin 2. All right? So this is kind of what we expect to happen is when there's angiotensin 2, it causes this, this, this, and this. What if I gave an ACE inhibitor or an ARB, guess what they're going to do? Ah, my friend, it's very good. You're going to take an ACE inhibitor or an ARB and you're going to shut down the angiotensin 2. If you shut down the angiotensin 2, you will prevent this increase in intraglomerular blood pressure. You'll prevent the excessive filtration. And you'll prevent the protein loss. And so that's why this is so great, is because you get a double whammy effect out of this thing. You inhibit protein. loss and you inhibit the renin angiotensin aldosterone system the renin angiotensin aldosterone system that is also causing the patient's blood pressure to be high so that's another beautiful effect out of this is that you also will block the renin-angiotensin-aldosterone system, will prevent the patient from having that secondary hypertensive effect. Beautiful. Everything else is pretty easy for the complications. Hyperlipidemia, diet, and then statins if that doesn't work. So diet changes, so diet changes, and then statins. For edema, it's fluid and sodium restriction. Try to minimize as much fluid and sodium that You're getting into the body that can help to reduce some of the edema. And then if that doesn't work, you can progress to diuretics, like loop diuretics. Hypercoagulable state. Because these patients are at very high risk for DVTs, PEs, renal vein thrombosis, if they have any of these incidences, you should really continue anticoagulation for these patients. So anticoagulation should be on the table for these patients as well. And because they have a high infection risk, what was the particular bacteria? Streptococcus pneumonia. You better make sure that these patients are heavily vaccinated against the pneumococcus. All right. So pneumococcal vaccination. And just a quick little kind of. of like cool tip is that in patients who have nephrotic syndrome not only is pneumococcal vaccination helpful but you know what else increases strep pneumonia type of infections edema. So if we want to basically inhibit streptococcus pneumonia not only should you vaccinate these patients but also reduce The edema. Because edema provides a nidus for strep pneumonia infections. So don't let them develop any of this edema. The last thing for the treatment is treating the cause. So we know the complications are all those results that we went into great detail about. Loss of immunoglobulins, decrease in antithrombin 3, hypoalbuminemia that's causing this, hyperlipidemia due to the hypoalbuminemia, and proteinuria due to the podocyte damage. This is the causes, minimal change, like mental, membranous nephropathy, diabetic nephropathy, everything. What I want you to realize is that there's the secondary and primary causes. So when I say this, I'm talking about, okay, secondary causes of nephrotic syndrome. This is basically everything that we went over. for each one. So in other words, if it's not primary minimal change disease, if it's not primary focal segmental glomerulus gross, if it's not primary membranous nephropathy, or if it's diabetic nephropathy, or if it's amyloid nephropathy you have to treat the underlying cause. So if it's secondary minimal change disease, secondary membranous nephropathy, secondary focal segmental glomerulosclerosis, and if it's diabetic nephropathy or amyloid nephropathy you have to treat the underlying cause. So in other words getting rid of NSAIDs, treating their infection, treating their Hodgkin's lymphoma, treating their hepatitis B, treating their hepatitis C, their syphilis, getting rid of the offending medications. treating their hiv telling them to stop doing heroin and also trying to control their sickle cells this one glycemic control using insulin if needed and this one depending upon the type of amyloidosis may require further like chemotherapy but that's the important thing is you have to treat The actual secondary cause, which is a little bit beyond, we can't go through every single one of these, but you have to treat the causes that we kind of highlighted. What we can discuss, and is important to discuss, is if they have primary causes of nephrotic syndrome. In other words, we don't know why. It's likely genetic, it's likely some type of autoimmune component, but we just don't know why. What are those? That is your primary minimal change disease, your primary focal segmental glomerulosclerosis, and your primary membranous nephropathy. So primary minimal change disease, primary membranous nephropathy, primary focal segmental glomerulosclerosis. How do we treat these? All of them, you're going to start them off on steroids. So you're going to start steroids because you're going to try to suppress their immune response. This one was a T-cell response. This one was some type of immune complex response. this one we don't even know how it forms. But steroids are going to be the first particular thing. Now, here's what's really helpful in diagnostics of the therapeutics, if that makes sense. If they have a good response to the steroids, so let's put that here, a really good response, that's highly suggestive of minimal change disease. And often times you can avoid doing the biopsy. That's why we don't always go to biopsy first. If there's a poor response to the steroids, guess who it likely is? It's your nasty primary ones that are in adults. Your primary member in a nephropathy or your focal segmental glomerulosclerosis. So in these, what did I tell you? Was the scary thing, I don't put primary, focal segmental glomerulosclerosis. What did I tell you was a big thing with these that they cause that this one does not cause? These can cause end-stage renal disease. So if they do not respond to steroids and you don't treat them any further, guess what these suckers can do? They can cause chronic kidney disease. So they can jack up those kidneys and lead to end-stage renal disease. Do we want... that? No. So if steroids weren't working, what can I do to reduce the risk of these patients developing chronic kidney disease? Then I can put them on long-term. And this is where we do the biopsy. So usually if you put a patient on steroids, they have a good response, it's likely minimal change. If they did not have a good response, it's likely these two, you probably should get a biopsy to confirm and then put them on long-term immunosuppressive therapy because you don't ever want to commit a patient to this if you don't really know. And so this is where you would do things like long-term immunosuppressants. And there's so many of these, I'm just gonna mention the biggest ones. The biggest ones that you'd wanna be able to remember here is gonna be something called, so we use cyclophosphamide, this is a pretty good one. And another one is called tacrolimus. These are other types of immunosuppressants that have been shown to be pretty beneficial in these patient populations. So again, think about long-term immunosuppressive therapy if they failed steroids to prevent the progression to chronic kidney disease. My friends, in this video, we covered nephrotic syndrome. I hope it made sense. I hope that you guys enjoyed it. And as always, until next time.

What's up Ninja Nerds? In this video today we're going to be talking about nephrotic syndrome. It's one of the types of glomerulonephritis.

It brings a lot of students a lot of fear and anxiety. I'm going to do my absolute best to make sure that at the end of this video you guys understand it. If you guys do like this video it makes sense, it really does help you, please support us.

One of the best ways that you guys can do that is by hitting that like button. commenting down in the comment section and please also subscribe if you guys do want to follow along with me we got some great notes some great illustrations that our team has worked together to make just some beautiful notes and illustrations for you guys to follow along with me and really understand this topic so go down in the description box below and it'll take you to our website where you guys can follow along with me but let's start talking about nephrotic syndrome so Before we actually get into the, you know, the kind of the meat and potatoes of nephrotic syndrome, I want to go over the basic functions, the anatomy of the glomerular filtration barrier. It's really important that we understand this because once we build on those basics, we can kind of really understand the pathophysiology.

So the first things first, as we talk about the glomerular filtration barrier, it's really just three layers. So I have it abbreviated, I'm going to abbreviate it as GFB, the glomerular filtration barrier, if you will. Now there's three different components of this barrier. The first one is going to be this red capillary here. So you know you have the glomerular capillaries, they're supposed to be what's called fenestrated.

So which means that they're a little bit porous and they allow for things, particularly selective things, to be able to move from the plasma of the blood into this actual Bowman space. So that's the first kind of component of this barrier here is you have what's called, let's actually do this one here in black, this is called your fenestrated capillaries. All right, so these are porous and they are allowing particular things to leave. through here but we want it to be very very selective though alright so we have finished rated capillaries the second component is this blue structure here you see that one right there this is a really interestingly negatively charged kind of membrane, if you will, and it's really nicely sticking and adhering to the finish rate of capillaries, but it's highly negatively charged. You know what's really interesting?

Proteins that run through our bloodstream, they're very negatively charged. So negative and negative charges should kind of repel each other. We know like and like charges repel one another.

So it's really good at being able to block large proteins from exiting the blood and coming into this capsule space. So that'd be the second component of the barrier here, which is going to be the glomerular basement membrane. The glomerular basement membrane. Now again, with this one, you need to remember it's that negatively charged membrane. So that's what's really cool about that.

So I'm gonna put this here, and like this thing here, negatively. charge just to remind you kind of that function. The third component of the glomerular filtration barrier is gonna be these like cells here. You see these like little cells? They're kind of like right next to the glomerular filtration, the glomerular basement membrane.

These are called your podocytes. So this is the third and last component of this filtration barrier. This is going to be the podocytes. Now the podocytes are really cool and what happens with the podocytes is they have like these little like you can't see them but you see like there's little divots there. They're called their foot processes.

And generally there's some spaces between them called filtration slits. And that's supposed to again allow for some degree of permeability across this filtration barrier. So the third component here is going to be the podocytes.

And again, the real significant component of this is going to be what's called your filtration slits. Alright, now you're probably wondering, okay, we got a little bit of basics here for nephrotic syndrome, I get it. Why is this so important?

Well, the glomerular filtration barrier is supposed to be very, very important in being able to regulate what leaves the blood and enters. into this space here, the Bowman space. We really only want certain things filtering out of the bloodstream and into the actual Bowman space.

We only want certain things, things like sodium, things like water, things like electrolytes and nutrients. But you know what we don't really want running through here? What we don't want to be leaving is we want the glomerular filtration barrier to block the loss of red blood cells, white blood cells, and proteins. And that's the job of this glomerular filtration barrier. Now imagine for a second you develop a damage.

To one of these three components of the glomerulofiltration barrier, are you going to be able to closely regulate what leaves the blood and enters into the bone and space? No. And so that's the important thing here, is that this whole membrane here, it's supposed to block the loss of red blood cells, white blood cells, and proteins.

There's two diseases that are a part of what we call glomerulonephritis. One is called nephrotic syndrome. So one is called nephrotic syndrome, and that's what we're going to be discussing.

Now nephrotic syndrome, really how it breaks down the glomerulofiltration barrier, if you will, is it really takes a hit to the podocytes. So what this son of a gun does is, is it really causes a lot of podocyte injury. So it causes a lot of podocyte injury. And so whenever you damage these podocytes, it's one of these actual particular components of the filtration barrier.

And then look what happens. As a result of the podocytes that are actually being injured, you lose the capacity to control what things are leaving the blood and entering into the Bowman space. Now out of all of these three, and we're going to hit on it a little bit more, the true one that actually ends up becoming the most affected is proteins.

And you're going to see a massive, massive amount of protein loss. So protein loss is going to be the heavy, heavy cause here that you're going to see in nephrotic syndrome. So the big, big bare bones things to understand for the glomerular filtration barrier is that, again, it's made with these three layers. But which one of the layers is damaged in nephrotic syndrome?

It's the podocytes that are injured. They are supposed to be controlling what leaves the blood and enters into the bone and space, particularly red blood cells, proteins, white blood cells. But the most important one.

is going to be proteins. And if you damage these podocytes, you're going to lose a lot of proteins. So that leads us into the next component here, which is nephrotic syndrome.

So we know that nephrotic syndrome, the basic concept of this disease process, which is again, it's kind of an umbrella. So when we talk about glomerular diseases or glomerulonephritis, it's the inflammation of the glomerulus. And this can present in a couple of different ways.

One of the ways that glomerulonephritis can present is in the nephrotic syndrome. Another way it can present is in nephrotic syndrome, which we'll talk about in another video. But nephrotic syndrome, so what we know is, we know right away that there's some type of podocyte injury, if you will.

And whenever you have this podocyte injury, what it's really going to be doing is... Is it's going to cause these poor little cute podocytes to become damaged in some particular way. And whenever you damage these podocytes, you technically, what you do is you kind of efface. So you see these like little foot processes?

You actually efface them. So you get rid of them. And then you kind of like make them flat and they lose the ability to really control permeability. And so what happens is, is you end up with what's called podocyte effacement. So you end up with some type of podocyte effacement.

And the problem with this is, we already kind of mentioned it, is this is going to lead to a heavy, heavy degree of protein loss. So what you're going to see is, as a result of this podocyte effacement, is you're going to see heavy, heavy degrees of protein. is being lost across the actual glomerular filtration barrier. So here, let's actually represent these as proteins. So here's all the proteins that I'm gonna be losing here across the Bowman space.

And they're gonna end up draining all up into the urine. So what you're gonna notice as a result of this podocyte effacement is you're going to notice what's called heavy, heavy proteinuria. So we notice something called proteinuria.

And we have to be very, very specific to the degree of proteinuria. I keep saying heavy. What I really mean is, is that the amount of protein that's truly being lost is very significant. We say it has to be greater than or equal to 3.5 grams of protein is being lost.

in the urine per day. So that's what I really want you to take away from this, is it's 3.5 grams or more being lost per day in the urine. That's one of the hallmark signs of nephrotic syndrome.

Secondary to podocyte injury and effacement, one of the components of the, again, glomerular filtration barrier. Now, When you lose protein in the urine, what happens is you have less protein that remains within the blood, right? So we know that here's the proteins we're going to kind of represent here.

They're supposed to be circulating through the bloodstream. They go through the glomerulus. Generally, it's not supposed to be getting filtered off, my friends, right? So what should happen is that when we leave, when the blood leaves this, so this is what's called your afferent arteriole, and this is your efferent arteriole. When blood comes out here, what should be the albumin level in normal people?

It shouldn't be very, very low. But in these patients who have nephrotic sin, When the blood leaves, guess what happens to their albumin levels in the blood? It drops.

And so does other proteins. So let's talk about that. So we end up with what's called hypoalbuminemia, which is low albumin within the blood.

This can cause a lot of problems, but what are some of those problems? So one thing is that we're going to have less albumin. in the blood. We can call that hypoalbuminemia. So, albumin within the blood.

Now, why is that a problem and what can that lead to? Well, albumin is a really interesting type of protein. It helps to regulate what's called osmotic. or oncotic pressure if you will.

So let's say that here I show these albumin proteins here that's in the bloodstream. Normally what it's supposed to do is, there's water that sits in the cells and in the spaces and they should get kind of sucked in or drawn into that actual space there. But as you lose albumin, you lose this oncotic pressure and you lose the ability to draw water into the cells.

Now, as a result, because of decreasing the osmotic pressure, what's the end result here? As you decrease the osmotic pressure or the oncotic pressure, they're both kind of similar terms, semantics. really, it leads to a lot of fluid staying in these tissue spaces.

And what will that look like to the patient when you look at them, you know, in person, it's going to give them a lot of edema. So a lot of fluid sits in these spaces and the ways that these present patients will present is they present with what's called edema. Now the question arises, what does edema look like? It can look like a lot of peripheral edema on their legs.

They could have pulmonary edema fluid in their lungs. They could have fluid in their belly, ascites. Or sometimes it can even sit around their eyes, periorbital edema.

So a lot of different problems here. That's one thing, is they can definitely have a lot of edema. What's another problem though?

I'm going to write it here, but I'm going to explain it up here. Another issue with low albumin... is it increases your lipids. So it increases your lipids.

You're like, wait, what the heck? How the heck does it increase my lipids? What you talking about, Willis?

When there's low albumin, albumin is made by the liver, right? And so your liver is like a little albumin sensor, if you will. And it senses the albumin levels within the blood.

And it says, oh, shoot, man, albumin levels below. Well, I'm going to have to compensate for this. And I'm going to start trying to pump up my production of albumin.

So it tries to go and synthesize albumin as a result. That's what it's trying to do. You know what ends up happening?

It also ends up making some other proteins that are similar. And these are called lipoproteins. So we call these things like VLDL and LDL.

And you know what these sons of guns do? These sons of guns increase your triglycerides. They increase your cholesterol.

and you know what ends up happening? These things get into the bloodstream so you have higher amounts of these. These things move right into your bloodstream right? So now look, look at this. You got increasing levels of these lipoproteins.

These lipoproteins will then circulate through your bloodstream. They'll go to the kidneys. And when they go to the kidneys, they'll filter out.

Look, you're going to filter out a bunch of different lipids. And some of these lipids will end up into the urine. Some of them will actually passively move into these tubular cells.

And tubular cells, just like other people, they don't like, you know, getting all fat. And so they decide to just die and shed off into the actual urine. And so then you get like some cells.

That are filled with a bunch of fat. And you know what we call this? What do we call this when you have tons of lipids within the urine? Oh, it's not too crazy. It's lipiduria.

So we can have what's called, I'll actually write this down here, you can have something called lipiduria and you can have another one here. So there's two terms that I want you guys to be familiar with. One is what's called lipiduria and the second one, which is the cells filled with all that fat, these are called fat fat, oval bodies. How original, right?

Sometimes when you look at them under microscopy and you really get a good look at them, they kind of look like what they call a Maltese cross. But I think this is the big thing that you need to understand is that in response to low albumin, your liver starts cooking up a lot of other lipoproteins, which unfortunately has an adverse effect, increases your triglycerides, your cholesterol. You leak a lot of that into the urine. You know, another problem is what happens if you have high triglycerides and cholesterol in the blood? You can't get up with all kinds of problems man.

So you'll see sometimes these patients Unfortunately as a result of all of these things in the blood So if these things are like just cooking up in the blood, you can see a lot of problems. Things like, you might have heard these terms like xanthomas, right? So these kind of like big things that form on tendons.

You can get these fatty like plaques around the like the eyes, so xanthelasma. You know what the worst case scenario is? These things can plaque up the blood vessels. And you can end up with what's called atherosclerotic cardiovascular disease, right? This can look like peripheral artery disease.

This can look like coronary artery disease or the worst case scenario, you can develop a cerebrovascular accident. So you see how having a lot of these nasty little molecules increase the risk of some lipid complications, but also leads to a lot of lipid loss within the urine. Okay, what else? Well, here's another thing you're like, oh geez. It causes Renin-angiotensin-aldosterone system activation.

All right, man. This albumin does some stuff, doesn't it? It's kind of odd. So, yes, when you have less albumin, it causes edema, right? Because of this osmotic pressure.

So we know how this will cause edema. But another thing is when you have less osmotic pressure, not only does it cause edema, but it decreases the amount of fluid that's in your vessels. Oh, what's that called?

Your effective arterial blood volume drops. So you have a drop in the effective arterial blood volume When you have a drop in the effective arterial blood volume, isn't that just like the circulating volume going around the body? Yeah You know why that's a problem? The reason that's a problem is is that tells the kidneys that hey, there is a very low perfusion There's low circulating volume. Can you do me a favor and can you pump up?

the renin angiotensin aldosterone system and it does and you know what the result of the renin angiotensin aldosterone system activation is is it causes your blood pressure to go up so what's the effects out of all of this well what we know is this can increase your blood pressure so let's actually make this nice and purdy here so we'll have it can increase your blood pressure you And it can activate sodium and water retention. So it can cause an increase in blood pressure. What's that whenever the blood pressure rises?

Hypertension. So this is another common feature. And it can cause sodium and water. Retention.

When you retain a lot of this, not only does that increase your blood pressure, but what happens if you retain a lot of sodium water? You get puffy. And they start developing features of edema. So they can get edema because of renin-angiotensin-aldosterone activation. and because of low osmotic pressure.

Son of a gun. So these guys just can't take a break, right? So we know now that they're losing tons of protein. The biggest one is albumin.

And we see all the negative consequences of that. But there's other proteins that can be lost. Another protein that can be lost, and it's really important to differentiate this between nephrotic syndrome, is it's called anti, I'm going to abbreviate it, antithrombin 3. So if you guys remember from our hemostasis lecture, antithrombin 3 is an anticoagulant.

What it's supposed to do is, is it should naturally, you know, there's molecules called factors 10. and another one called thrombin. And these are supposed to, what they want to do is, these molecules want to go and stimulate their procoagulants. They want to stimulate a clot.

That is what they're designed for. to do they want to stimulate a clot to form all right that's their goal is to increase clot formation well you know antithrombin 3 is supposed to do antithrombin 3 is like on daddy you ain't gonna do that I'm going to inhibit you from being able to function and so antithrombin 3 naturally is supposed to inhibit these but if you have less antithrombin 3 are you gonna be able to inhibit these proteins no and so what happens is you aren't able to do this particular function because of a decrease in this molecule. And then these things go haywire, and they increase your clot formation.

What does that look like? Well, you get clots, my friend. And usually this is venous clots.

And so it can form in the leg. So watch out for those DVTs. They can break off, get stuck in the lungs, a PE.

And a weird one is what's called a renal. vein Thrombosis, this is kind of rare, but if you think about this in the context of nephrotic syndrome, it is relatively common, okay? All right, what else we lose one other protein and that's these little dudes. These are supposed to be Plasma cells, but if you're losing more than your plasma cells are able to produce these are called immunoglobulins or antibodies Immunoglobulins Now you're jacking these things up.

These are supposed to go and fight off bacteria You know the very specific bacteria that for some reason patients with nephrotic syndrome are super super susceptible to It's called streptococcus pneumonia And what happens is you have less of these antibodies. So are you able to bind up this bacteria, enhance opsonization, complement pathway activation? Nope.

You lose this. Strep pneumonia starts going on the rise. And if it gets on the rise, guess who likes to plague and increase the mortality for these patients?

Son of a gun. It loves to hit the lungs. And so you can end up with a nasty, nasty pneumonia.

And so as you can see, the complications of... having less of these immunoglobulins is you're going to be at very high risk of infections. So you're going to have infection risk that's going to be a little bit higher than most people.

And that's the problematic issue. And I think the big boards question that you can see for this is it streptococcus pneumonia and usually streptococcus pneumonia is the most common cause of community acquired pneumonia. So you want to watch out for that pneumonia in these patient populations.

So, at this point we've talked about nephrotic syndrome, what it really looks like when you damage those podocytes. But the question that arises, what's causing the injury to the podocytes? Let's talk about that. All right, my friends, so now we have to talk about the reasons the podocytes are damaged or injured and we're losing all this protein. So the first one that I want to talk about is called minimal change disease.

So before we even talk about that, there's three particular types of nephrotic syndromes that really are what we term primary meaning that we don't really know the reason why these are occurring they're what we call idiopathic there may be some genetics or autoimmune things but we just don't know then there's what's called the term secondary causes of nephrotic syndrome which you can see in every single one of these okay but just remember that the ones that we call primary nephrotic syndromes is minimal change memory nephropathy and focal segmental glomerulosclerosis you I'll explain that a little bit more as we go along. But first thing is minimal change disease. So a minimal change disease, it can be primary. We don't know the reason why it happens, okay? So when I say primary, primary for these three accounts for 70 to 80% of the nephrotic syndromes.

That's insane. So most of the time, it's primary. But when I say primary, we don't know why it happens. So we'll use this term idiopathic, meaning we don't know.

But there is secondary causes, meaning that we've seen some association of this disease with these particular things. And what they've seen is for the secondary causes, they've seen things like infections, like upper respiratory tract infections. and Hodgkin's lymphoma. The only other one is NSAID use.

So you can also add that one in as well. So NSAIDs have also been kind of linked to this. Now, how exactly these things do this next step, we just don't know. And I always feel bad for that, but I don't have an answer. But what we know is, is that these particular things, whether it's idiopathic or it's secondary, what they do is they stimulate T cells, all right?

And these specifically target these T cells to go to the kidney and release tons of these cytokines. And what these cytokines do is, is they go and they cause damage to the podocytes. And really all they do is they rip the foot processes off. So what you get is, you get what's called podocyte effacement, which we talked about. And that's really the interesting thing with this.

And then as a result of the podocyte effacement, and What do you lose a lot of in the urine? You lose a ton of protein in the urine. How much? Just to test your knowledge.

Greater than 3.5 grams per day. And you also can lose a lot of lipids in the urine. So you can get that lipiduria, right?

Now, the big concept for this is, again, we're knowing that these cytokines, by some particular means, are injuring the podocytes. They're getting effaced. And these podocyte effacements are increasing. the protein loss, and then subsequently from a lot of albumin being lost, a lot of lipiduria. So you're getting podocyte effacement from increased cytokines.

And here, we'll just kind of draw this here so that you see. you're damaging these podocytes. Now that's really the key thing.

So when I say minimal change, think about a young child, all right? And it's usually either primary, idiopathic, we don't know, or secondary, something else has been associated with it. Infections, maybe even immunizations, Hodgkin's lymphoma, and NSAIDs.

All right, that's enough said. Membranous nephropathy, again, can be primary, but thank goodness we have something to link with it. So in primary causes there's this weird antibody and it's called anti-PLA2 receptor antibody and it's for some reason loves one of the proteins in the podocytes. It loves one of those proteins. And it loves to attack it and efface the podocytes.

If I were to say secondary causes, then you're thinking about things that have been associated to lead to antibody activation. And this is things like hepatitis B, hepatitis C, syphilis, and there's one other kind of weird one. There are these two weird medications.

One is gold. and the other one is called penicillamine. But these are the weird things that for some reason have been associated with membranous nephropathy. Now, regardless of what that may be, what happens is, is you get some type of antibody.

that is actually going to be in some way binding with one of these antigens or the antigens that are present here. And so you're going to either get like these immune complexes and what they do is they go in and they deposit here right into the what's called the sub epithelial layer all right and when they deposit in there look at this you get all these kind of like deposition here this could be the anti-pla2 antibodies or this could be all of the other antibodies from hepatitis syphilis etc but you get a lot of antibody deposition so what's the result of this is you get what's called sub epithelial Sub-epithelial immune complex deposition. And when these suckers deposit into this area, they trigger an inflammatory reaction.

And what they do is, this subepithelial immune complex, they activate complement proteins, my friend. So you're going to activate these complements. You guys remember those? The C3, C4, all those things that come in there and really trigger a lot of inflammation. So what you're going to do is, is you're going to stimulate the complement system.

And when the complement system gets in there, it's gonna jack everything up. And then as a result, you're gonna get podocyte effacement. But you also get one more thing. When that complement system gets in there and really starts revving up a lot of activity and getting super inflamed, not only do you get a lot of podocyte effacement, But you also start causing some other problems, which is the glomerular basement membrane starts kind of having a reactionary thickening.

So the GBM will start thickening. It's going to get thick. And when you get this GBM thickening, it does something kind of like weird, where when you actually kind of like zoom in, and we'll talk about it a little bit later, here's your glomerular basement membrane, all right?

And then what happens is you have your kind of podocyte. that would be on this side here. So we'll kind of give them a little bit of space here. Here's your podocytes.

Look, their foot process is gone. All jacked up. But what happens is right in here is going to be your immune complexes. All these things that we're depositing. You know what the GBM does when it thickens?

It does something weird where it kind of like thickens outwards. And when it thickens outwards It gives this weird type of appearance that we'll talk about later. And it's called a spike and dome pattern. So we call it a spike and dome type of pattern. And that's really, really interesting that you get with this GBM thickening, okay?

All right. So that's what we get for membranous nephropathy. So when I say minimal change disease, you think child, idiopathic.

Secondary, you think like infections, maybe NSAIDs, Hodgkin's lymphoma. Membranous nephropathy, primary, it's one weird antibody. And if I were to say the...

primary if I put the primary here what would that primary antibody be it would be anti-pla2 receptor antibody this is the one that's the primary cause if it's not this antibody then you have to remember it's an immune complex where antibodies bound to one of these things and then deposited into that space. Okay? All right. Let's come on to the next one.

The next one here is focal segmental glomerulosclerosis. Now, with this one, The big thing to remember here is this can also be primary. Believe it or not, it tends to be, out of all of these, like the primary causes, this one is the most common to be the primary type. So if we talked about particularly all of these different types of diseases for...

nephrotic syndrome this is one of those that the primary causes is the most common there really isn't many secondary causes but we'll talk about those rare situations so primary I want you to associate with idiopathic right we don't know why something genetic we just don't know secondary there has been a couple things that have been linked to this HIV heroin use, dang, and also sickle cell disease. There also has been an association with like obesity, but I think these are the ones that you're more likely to see on the exam. Now, what happens with this one is again, we don't know. I don't have an answer as to why these things happen, but something occurs where you activate a lot of like sclerosis and hyaluronosis of of parts of the glomerulus.

That's why we call it focal and segmental. It's not the entire thing. So imagine like right here in this area, I'm gonna have a lot of sclerosis right here in this particular area.

So there's gonna be a lot of sclerosis and then we'll use like a different color here. Maybe we'll do like a little bit of pink or something. And this will represent the hyaluronosis.

So you're gonna get kind of like a hyaluronosis and sclerosis of parts of the glomerulus. Weird, right? We don't know why, but it just happens.

So you can get what's called hyaluronosis and sclerosis of the glomerulus. The glomerulofiltration barrier, if you will. And what this does is this causes podocyte. So you're noticing a trend between these three primary types of disorders is that no matter what it may be, you're getting some degree of podocyte effacement.

And this one is going to be due to a lot of hyaluronosis, and sclerosis of that glomerular filtration barrier. Now, that's the big thing to remember for these. Okay?

Now, here's the next thing with this particular disease. With focal segmental glomerular sclerosis, and membranous nephropathy, because you can cause potentially over time a lot of damage to these kidneys, it's important to remember that in situations where these patients have focal segmental glomerulosclerosis and membranous nephropathy, so in diseases such as membranous nephropathy and focal segmental glomerulosclerosis, these can really plague the kidneys. They can really do a lot of damage if they're not treated. And what can happen is as you continue to plague these kidneys and injure them and injure them and cause inflammation and fibrosis, you can literally progress these kidneys into something called chronic kidney disease.

But these are really the only two that have that higher risk of end-stage renal disease or chronic kidney disease. Minimal change disease, not so much. All right, we go on to the next one.

Diabetic nephropathy. So at this point, we're now talking about only secondary causes of nephrotic syndrome. So what are the reasons the podocytes are being injured or damaged in some way, shape, or form?

For the primaries, it was minimal change, membranous nephropathy, focal segmental. If it's not primary, which is usually the most common cause for those, meaning it's idiopathic and we don't know why, then there's some random secondary ones that we talked about. But for these, it's only secondary causes. So it's some systemic disease that causes nephrotic syndrome.

diabetes or amyloidosis. So obviously in diabetic nephropathy the hint to knowing this one is you got a patient with diabetes and what's the problem with diabetes what does it really do well you got that high glucose right and what that glucose does is it causes if you guys remember that non enzymatic glycation of the efferent arterial whoo shoot so you get what's called efferent arterial hyaline arteriolo oh my gosh so many words sclerosis and what that does is it makes it super impossible for blood to leave the glomerulus and then the glomerular blood pressure is like crazy high and you hyper filtrate we already talked about this before right but what happens is your intra glomerular blood pressure rises Narylofiltration rate would rise and so you're gonna have to compensate and protect the kidneys from that high pressure my friends. And so what you do is you cause GBM thickening and you cause sclerosis in a nodular pattern.

And what this does is when you thicken up that GBM, it causes the podocytes, the foot processes to be farther away from one another. So it causes the podocyte foot processes to stretch out. the same way of causing podocyte dysfunction. And if you do that, you're going to get the heavy proteinuria because you're causing podocyte dysfunction. So in this particular situation, what we know is the increase in efferent arterial high arteriosclerosis reduces blood flow out of the glomerulus, increases the blood pressure, increases the GFR, thickens the glomerular base membrane, causes sclerosis, and then effaces those foot processes.

And that is how we end up with this heavy, heavy degree of protein loss. The other thing is that with this over time, the sclerosis and nodules, you can lead to what? Chronic kidney disease.

My friends, what is the most common cause of chronic kidney disease? Diabetes. And this is because it's going to damage and cause tons and tons of sclerosis to the kidneys that they...

will progress to chronic kidney disease. If I were to ask you what's the most common cause of chronic kidney disease, you should say diabetic nephropathy. If I were to say what's the most common cause of nephrotic syndrome, you should say diabetic nephropathy. And that is the important thing. thing to remember for this one.

The last one here is just kind of a weird one. We got to talk about it unfortunately because it's a part of the nephrotic syndromes, but it's amyloidosis. And this deserves a quick discussion as to the two types of amyloidosis. So there's what's called AL.

So AL, amyloidosis, that means light chain amyloid proteins. You know there's a disease where you produce lots of these light chains unfortunately? Multiple myeloma.

So in patients who have multiple myeloma, they're at high risk of injury to their kidneys. We know that that's one of the features, right? Multiple myeloma.

If you guys remember like that crab mnemonic, the hypercalcemia, the renal failure, the anemia. the bone pain, that's one very particular significant feature. The other one is what's called secondary amyloidosis, which means there's something that's causing chronic inflammation which is leading to a lot of these amyloid proteins to be produced.

You know what that disease is called? It's really any disease that has chronic inflammation. What's a big one?

RA. Rheumatoid arthritis causes a great degree of inflammation. But the difference is in really just the protein kind of like structure and composition.

But either way, the same kind of thing exists between these, which is your body is, regardless of what the structure of them is, your body is producing an increased amount of abnormal proteins. And so, That's the whole point with this one is you're getting a lot of abnormal proteins, my friends. And when you get a lot of these abnormal proteins, guess where they decide to go?

In the same situation here, my friends, they like to go here and they like to deposit into the glomerular filtration barrier. And when they deposit, what they do is they cause a lot of inflammation. And guess what they do?

They do the same thing that this diabetes does. They cause GBM thickening. So they thicken up that glomerular basement membrane, so they cause GBM thickening, and then they also cause a lot of inflammation and then sclerosis, so they cause a lot of sclerosis of the glomerulus as well, somewhat in a nodular pattern.

But if that happens, what's the end result that we saw within diabetes? Same kind of thing. You're getting the foot process effacement. I'm sorry.

You're actually stretching out the podocyte foot processes. I apologize. Which is the same thing because you're causing podocyte dysfunction, leading to the loss of the good filtration barrier and proteins to get lost.

loss. The other thing is with the sclerosis, what can you also progress this thing to? Chronic kidney disease. So you're noticing a trend with all of these nephrotic syndromes. The only one that really won't really progress to renal failure is which one?

Minimal change disease. The ones that can progress to renal failure that are primary is membranous nephropathy and focal segmental glomerulosclerosis. The ones that can progress to chronic renal failure is going to be diabetic nephropathy and amyloid nephropathy. We've gotten the causes, minimal change, membranous nephropathy, focal segmental, diabetes, and amyloid.

The question then comes, because A lot of this, this is a lot of information. How am I supposed to know which one it is off a patient who comes in with some vague symptoms like some edema, right? Or maybe they have high lipids, or maybe they have hypercoagulable states, or maybe they have increased risk of infections. They got a lipid in their urine, they got a protein in their urine. How am I supposed to know?

Let's talk about that. All right, my friends, so we have a patient that we think may have nephrotic syndrome. So sometimes looking at the physical exam features that we talked about, kind of the effects of nephrotic syndrome, really was looking for any features of edema, right?

So periorbital edema, pitting lower extremity edema, pulmonary edema, ascites, that could be one thing. Or if they come in with a history of recurrent DVTs, PEs, renal vein thromboses. If they have complications of hyperlipidemia, xanthoma, xanthelasma, cardiovascular events. Or if they come in with increased risk of infections, like particularly streptococcus pneumonia. Now, with this being said, this is very vague, right?

So oftentimes what ends up happening is if we have a patient who has like some degree of edema. We may get a urinalysis and microscopy. And the reason why this is kind of helpful is because this leads us into the next topic that we'll talk about in another video called nephritic syndrome. But I want to introduce it. I want you guys to be able to compare, contrast, differentiate these two.

It's very important for your exams. So a urinalysis and microscopy is really good. It just doesn't quantify the protein loss as much, which is really, really important.

But it gives you an idea, hey, there's a heavy amount of protein, there's some other weird stuff in here too. This is where it's really good at being able to differentiate between nephrotic and nephritic syndrome. So the basic, basic thing for nephritic syndrome is it's inflammation of the glomerulus causing glomerular basement membrane damage. Whereas nephrotic syndrome was inflammation of the glomerulus causing podocyte damage.

Alright, both of them either way lead to loss of particular things into the urine. Nephrotic syndrome causes heavy proteinuria and lipiduria. Nephritic syndrome leads to everything being lost. Red blood cells, white blood cells.

cells and protein. Would I be able to differentiate that off of a urinalysis with microscopy? Absolutely I would. So when I go look at nephrotic syndrome and I get a urinalysis, one thing I'm going to notice is I'm going to have two big things for nephrotic syndrome, two big things I notice in the urine. One is I'm going to have a massive, massive amount of protein and I'm going to have a lot of lipids.

And if I look under microscopy, I'll also see those weird fat oval bodies, right? So I have a lot of what's called lipid urea. And if I look under the microscope, I can see those fat, oval, bodies, right, that we talked about in the lipid urea situation.

The other thing is I'm going to have a lot of protein. Problem is, is I'm not going to be able to quantify this. So the dipstick kind of gives you like a plus one, plus two, plus three amounts of proteins.

I'll have a lot of protein. So plus three, plus four protein urea. But it's not good at telling me the true amount that I need to know.

Is it greater than or equal to 3.5 grams per day? I won't be able to get it off just a basic urinalysis. All right.

So that's not crazy helpful, but it's at least something. Here's another thing. Nephritic syndrome, I told you. So again, this is podocyte damage.

Podocyte dysfunction, if you will. Whereas in nephritic syndrome, it's glomerular basement membrane dysfunction is the basic pathophysiology. They both lead to heavy leakage. Now, the difference between this one is a little bit... different.

So we're going to have protein, but it's not going to be as much. I'm only going to give it one arrow. We're going to have a lot of red blood cells and we're going to have a lot of like white blood cells.

Huh. So what will I have? here I'll have some protein but it won't be as significant of the protein maybe this is like plus one plus two it's like plus three plus four still not great but it's okay but here's what's the big difference between these I'm gonna have hematuria and when I look at this red blood like the actual blood under the microscope I noticed something called red blood cell cas and that's usually a buzzword term for nephritic syndrome the other thing is I'll have what's called pyuria which is white blood cells, but sometimes people would be confused and they'd be like, oh, white blood cells, doesn't that mean there's an infection?

This is what we call sterile pyuria. So it means that there's actually no evidence of infection, there's just a lot of white blood cells that leaked across the blood into the actual Bowman space. So that's kind of the basic differences. It's not enough, but it at least gives you kind of a basic beginning. I could at least tell off the urinalysis with microscopy which one's likely nephrotic, which one's likely nephrotic.

But it's not stone cold kind of definitive. So then what I would do is I would do what's called a 24-hour urine protein or what we call a urine-albumin-creatinine ratio. So this you have to collect urine over a 24-hour period.

That sounds very tedious, very annoying, probably not the most desirable thing to do. This one is what we call a spot. Urine analysis. We do it one time.

People like that a lot more. And so they both are pretty good at giving you the amount of protein that you're losing in your urine over a 24-hour period. That's really helpful because I know in nephrotic syndrome, which is podocyte dysfunction, I'm going to have a lot of protein.

But how much protein? How much do you have to have to truly be considered? Because you're going to get proteinuria here.

There's still protein loss. But what is the big difference here? So I'm going to have protein loss in both of these.

This one I already told you will be crazy high. This one will just be a little bit high. But what's the true number over a 24 hour period that we need to have? This happens.

to be greater than 3.5 grams per 24 hour period and this has to be less than 3.5 grams per 24 hour period that is the big difference and that will set this apart between the two. So if you have heavy proteinuria with lipiduria, no hematuria and no sterile pyuria, it's more likely to suggest nephrotic syndrome. If you have hematuria, pyuria, and sub-nephrotic range proteinuria, less than 3.5 grams per day, it's more likely to be suggestive of nephritic syndrome because they both can have edema, which we'll talk about. They both can have hypertension, which we'll talk about, and they both can lead to renal failure, which we'll talk about.

It's really this that helps you. Another thing that can be somewhat helpful in differentiating nephrotic versus nephrotic syndrome is in nephrotic you have a heavy amount of protein loss. But I was very specific.

What was the most significant protein that was lost? There was a lot of albumin. There was a lot of albumin loss. And what did we say we would be able to determine off of the albumin in the bloodstream? Well, I told you that because this disease, there's podocyte dysfunction, it causes a lot of, here's our blue color here.

a lot of albumin to get lost. So there's going to be a ton of albumin in the urine. What happens to the albumin that leaves the glomerular capillaries and goes into the efferent arteriole and into your circulation? What is it going to be here?

It's going to be very low. So if we were to check the serum albumin levels, their albumin within the blood would be very low. And so they would have very low albumin levels within the blood. And we also can kind of make a little connection here that we said that when the albumin levels in the blood are low, what did that do to the liver? Stimulated the liver to pump what out into the bloodstream?

Lots of lipids. Unfortunately, as the result of trying to make more albumin, right? And so if I were to test the blood, what would I find a lot of in the blood as a result of the heavy albumin loss? I would find a lot of... VLDLs, I would find a lot of LDLs, and maybe I would even find a lot of like high triglycerides as a result here.

So you're going to notice that these patients will have features of hyperlipidemia on their lipid panel. Okay. And this again adds to the definitive shot of saying, oh, it's nephrotic syndrome. So if I've done all of these, I should be able to get to the point where I say, I know it's nephrotic syndrome causing some type of podocyte dysfunction, leading to heavy proteinuria and lipiduria.

Then we got to get to the next step. Which one is it? Which is the cause of the nephrotic syndrome?

Is it minimal change? Membranous nephropathy? Focusegmental? Diabetes?

Amyloid? Zach, I don't know what to do. I got you. Let's go. Now we move into the next step here, which is we don't know which one it is.

Is it minimal change? Is it membranous? Is it focusegmental? Is it diabetic?

Is it amyloid? How am I supposed to figure this out? Remember I told you that out of all of those causes, it's likely going to be, again, primary causes as one of those big things. for minimal change or for membranous nephropathy or for focal segmental glomerulosclerosis. On the rare occasion for those three diseases, there could be secondary causes that we said have been associated with it.

Those are things to think about and you could test for those things, right? Because right now we've already just gotten to the point, I know it's nephrotic syndrome, I just don't know which one it is. Look for specific hints. that may be suggestive.

So for minimal change disease, I already said look for like a young child. So I think that's one of the big things to think about is a very young child because it's more common. It's one of the most common nephrotic syndromes in children. So right when you see that with nephrotic syndrome features, you want to think about minimal change disease. That's one way that they'll try to get you.

The second one is we said that it could be associated in some way, shape, or form with Secondary causes such as what? Infections. It could also be due to Hodgkin's lymphoma or it could be seen in association with insets.

So look for that. Look for Hodgkin's lymphoma in the vignette in a child which would be really sad. Look for insets in the vignette with a little child or look for some type of infection or even sometimes recent immunization for a child.

Okay, but out of all of these ones, this is probably going to be the one that when you just bings up off the exam It really will help you to make that differentiation. Okay Now these are the secondary ones. It doesn't account for the primary one, which is we don't know why it happens, right?

So that's why sometimes these three can be difficult to diagnose because if it is primary these things won't come up as very helpful For membranous nephropathy, what you really want to look for in the question stem is someone who is Caucasian, right? And this is usually an adult. So it's some type of Caucasian adult. And this is usually the epidemiological range where you can see this one.

The other things that you want to watch out for is those infections. So you can test them for things like HIV, right? You can test them for things like hepatitis.

You can test them for things like syphilis. I apologize. This one is specifically hepatitis B virus, hepatitis C virus. You can test for that. You can do the RPR, right?

Testing for syphilis. If you believe that that could be a potential cause and then look for any medications in their history. So look for those particular medications that I told you, which was gold or penicillamine.

So look for gold or some type of penicillamine. Now, this is for the secondary causes, right? I told you that there is one particular primary thing that we can test for, and I'll talk about it down here in a little bit, but it was that anti-PLA2 receptor antibody.

You can test for that, but that's not a secondary cause, that's a primary cause. So again, that would be the big thing that would kind of ping off here is maybe this or potentially some of these for the focal segmental glomerulosclerosis you want to look for some type of african-american horse Hispanic male Hispanic adult These are usually the big things for this. So look for some type of African American or Hispanic adult. So again, what you're already noticing is that this could be one way of helping you to kind of stratify and differentiate is the child versus the adult.

It'll automatically kind of like point to these two if it's adult. It'll kind of like point to this one if it's a child. So look for that.

The other thing is we did say that this could be associated with HIV. So you go to HIV. you can do HIV testing and this can also be associated with heroin use.

So looking for that potentially in their history as well as things like sickle cell and looking for obesity as another factor. Now these ones I think are probably going to be the easiest secondary cause. And I, again, I stress this. What's the most common cause of chronic kidney disease?

Diabetes. What's the most common cause of nephrotic syndrome? It's diabetes.

So diabetes is an easy one that you can obviously elucidate. Look for a history of diabetes, but ones what's the most common cause of nephrotic syndrome? Diabetes.

what's one thing that I can do and I can test for to find if they have diabetes? A hemoglobin A1C, right? So that's usually gonna be the biggest diagnostic tool here is a hemoglobin A1C, like, you know, generally we like to see greater than 7% to really be a true effect on the actual kidneys.

All right, but you know, generally by definition, it's anything like greater than 6.5%. But usually when you get to greater than seven, you start seeing a lot of kidney damage. All right, for amyloidosis.

The big thing for this one is if you're really looking for amyloidosis, you want to consider things for multiple myeloma, right? Or a lot of this antibody deposition in other areas. So we can do two other tests if you're ever concerned for it.

You can do what's called an S-PEP or a U-PEP. And that's usually very, very helpful for multiple myeloma. But if it's not completely clear, another one that you could do is you could do what's called a fat pad biopsy. And that's also very helpful. helpful for being able to identify amyloidosis.

And that's why when you have a patient who has nephrotic syndrome and they have amyloidosis or diabetes it is very rare that you would ever get renal biopsies on these patients because diabetes is the likely cause and if they have a history of diabetes it's likely that and if they have a history of amyloidosis or you think it's amyloidosis I can kind of go away from doing a renal biopsy and do a fat pad biopsy okay but for completeness sake for the lecture you could consider doing a renal biopsy if there's an unclear cause of the nephrotic syndrome. In other words, it's a primary type, minimal change, membranous nephropathy, focal segmental, and it's idiopathic. I don't know why. There's no cues, there's no keys that really kind of buzz out and help me very much.

That's where a renal biopsy would really kind of solidify this. But again, I need to make sure that you guys understand, for diabetic nephropathy and for amyloid nephropathy, it's relatively rare that we would obtain these particular studies. Even in minimal change disease, it's kind of rare that you would obtain it just because this is in children. Renal biopsies are relatively contraindicated in children less than 10 years of age. So it would also be something that you might not be getting.

But if you did get the renal... biopsy, what they do is they take a chunk of tissue out and they take that tissue and they look at it under three different types of ways. One is they look at it in what's called light microscopy, electron microscopy, and immunofluorescence.

All right, basic things for this one. Light microscopy gives you general details. There's some general basic look at the glomerulus.

Electron microscopy zooms in on the podocytes. That's what I want you to remember. General look at the glomerulus zooms in on the podocytes.

Immunofluorescence looks for antibodies or some type of immune complex that are deposited in the glomerulus and lights it up a beautiful fluorescent green. That's it. General change zooms under the podocytes, looks for antibody or immune complex deposition, and lights them up green. That's what this is helpful for.

And already I can tell you which ones are beneficial. Minimal change is the beautiful name. It's a beautiful name because really there's only one thing that's happening with this. It's podocyte effacement.

So if I'm effacing the podocytes, what would be, out of all of these, the test that would be very helpful? Electron microscopy. So the electron microscopy is going to be the best particular test here because what it's going to show me is the podocyte effacement. The light microscopy and immunofluorescence will be completely normal.

That's why it's a very minimal change. But membranous nephropathy, I said that there was immune complexes. They were depositing.

into this particular area here. So they were depositing all up in this area here, really causing a lot of problems. So if I were to do these, I could actually see something in each one. If I did light microscopy, I may see something. What would I see?

Generally you see a lot of just thickening of the glomerular basement membrane. If I did electron microscopy, I zoom in on the podocytes. What would I see in the podocyte area?

I would see effacement of the podocytes. But what else would I see? I'd see a lot of these immune complexes deposited in that subepithelial layer. and immunofluorescence, it's the one that's going to be the most helpful. Why?

Because I'm gonna light this thing up beautifully green, showing that there is these antibodies that are depositing and kind of this nice granular fashion in that area. Okay, so this will show GBM thickening. This will show that spike in dome pattern with podocyte effacement from the subepithelial deposition. And this will show a nice granular green pattern.

This one, for this one, if I did light microscopy, it'll give a general look. And what it will show is it'll show a lot of that hyaluronosis. and sclerosis. So to show a lot of hyaluronosis and sclerosis of segments and parts of the glomerulus.

On electron microscopy It'll zoom in on the podocytes and show podocyte effacement. So for each one of the electron microscopies, what should you see? Podocyte effacement.

Which one will only have immunofluorescent positive? Membranous nephropathy. Which one will only have hyaluronosis and sclerosis?

Focal segmental glomerulosclerosis. And which one will have GBM thickening and a spike in dome pattern due to the immune complex deposition? Membranous nephropathy.

That's it. So that's why these are relatively easy if you do a biopsy to identify. These ones you won't be doing it because it's really off their history and you can avoid biopsying these patients.

But if you did. Really, you could get most of your information off of these because what you're going to notice from these patients is they're going to have a lot of that nodular sclerosis. We call this the Kimmel-Steele-Wilson nodules. That's going to be pretty obvious off their kind of light microscopy. So you can honestly just do like light microscopy for these patients and be able to notice those Kimmel-Steele-Wilson nodules.

Same thing for amyloid nephropathy. You're going to be able to notice a lot of like that sclerosis. Of the actual glomerular filtration barrier and it can be nodular but here's the key thing They stain it.

Hey, they they stain the actual the biopsy tissue And what you look for is this weird thing where the amyloid proteins when you stain them with what's called a Congo red stain They light up like an apple green color. So you go it's called apple green Bifrigen on a Congo red stain of this biopsy. All right So I know this is a lot, but I just want you to get the basic idea that we would only go to the renal biopsy, usually if it's a primary type of nephrotic syndrome.

So minimal change, membranous nephropathy, focal segmental, where it's idiopathic. We don't know the cause. Rarely for amyloid and diabetic.

Okay? With these, you can get a good amount of findings to truly differentiate which type it is. Now, that leads to the last step here, which is how do we treat nephrotic syndrome? Let's talk about it.

All right, so we've come to the point where we've said, okay, it's nephrotic, it's not nephrotic. We figured out the cause. If it was minimal change.

Focusegmental, Membranous Nephropathy, Diabetic, Amyloid. If we were really kind of not sure, we could do the biopsy if we need to, to really delineate it based upon electron microscopy, light microscopy, immunofluorescence. We got to the point where we go, I know the patient has nephrotic syndrome.

It's easy to treat this because you're treating the complication and then you're treating the cause. And the complications are very straightforward. We should know this.

Proteinuria, you're losing tons of protein. This is the only one when I want to mark the kind of mechanism just quickly because a lot of these are straightforward. and it makes your treatment, you know, remembering these very easy. This is the only one I want to go into a little bit more detail for.

So for proteinuria, obviously kind of maybe controlling the diet. So not kind of restricting proteins, but really trying to just limit excessive amounts of protein. And then the other one is ACE inhibitors and ARBs, if their blood pressure tolerates. And believe it or not, these patients also have that hypertension from the renin-angio. angiotensin aldosterone system.

So they will likely tolerate it. But I want to explain how this helps. Okay. So we know that in this patient who have nephrotic syndrome, their angiotensin 2 levels are usually high because of the RAS activation, right? So if you have high angiotensin 2, what that does is it basically causes efferent arterial vasoconstriction.

So watch this. Look how narrow this sucker is going to be. There's like no blood. leaving that glomerulus. All right?

And so because of this, one of the problems is that whenever you have high angiotensin 2, we said it increases the intraglomerular blood pressure, that increases the GFR, and this increases the protein loss. All right? So this is kind of like that downstream effect from high levels of angiotensin 2. All right? So this is kind of what we expect to happen is when there's angiotensin 2, it causes this, this, this, and this.

What if I gave an ACE inhibitor or an ARB, guess what they're going to do? Ah, my friend, it's very good. You're going to take an ACE inhibitor or an ARB and you're going to shut down the angiotensin 2. If you shut down the angiotensin 2, you will prevent this increase in intraglomerular blood pressure. You'll prevent the excessive filtration.

And you'll prevent the protein loss. And so that's why this is so great, is because you get a double whammy effect out of this thing. You inhibit protein.

loss and you inhibit the renin angiotensin aldosterone system the renin angiotensin aldosterone system that is also causing the patient's blood pressure to be high so that's another beautiful effect out of this is that you also will block the renin-angiotensin-aldosterone system, will prevent the patient from having that secondary hypertensive effect. Beautiful. Everything else is pretty easy for the complications. Hyperlipidemia, diet, and then statins if that doesn't work. So diet changes, so diet changes, and then statins.

For edema, it's fluid and sodium restriction. Try to minimize as much fluid and sodium that You're getting into the body that can help to reduce some of the edema. And then if that doesn't work, you can progress to diuretics, like loop diuretics. Hypercoagulable state.

Because these patients are at very high risk for DVTs, PEs, renal vein thrombosis, if they have any of these incidences, you should really continue anticoagulation for these patients. So anticoagulation should be on the table for these patients as well. And because they have a high infection risk, what was the particular bacteria? Streptococcus pneumonia.

You better make sure that these patients are heavily vaccinated against the pneumococcus. All right. So pneumococcal vaccination.

And just a quick little kind of. of like cool tip is that in patients who have nephrotic syndrome not only is pneumococcal vaccination helpful but you know what else increases strep pneumonia type of infections edema. So if we want to basically inhibit streptococcus pneumonia not only should you vaccinate these patients but also reduce The edema.

Because edema provides a nidus for strep pneumonia infections. So don't let them develop any of this edema. The last thing for the treatment is treating the cause. So we know the complications are all those results that we went into great detail about.

Loss of immunoglobulins, decrease in antithrombin 3, hypoalbuminemia that's causing this, hyperlipidemia due to the hypoalbuminemia, and proteinuria due to the podocyte damage. This is the causes, minimal change, like mental, membranous nephropathy, diabetic nephropathy, everything. What I want you to realize is that there's the secondary and primary causes.

So when I say this, I'm talking about, okay, secondary causes of nephrotic syndrome. This is basically everything that we went over. for each one. So in other words, if it's not primary minimal change disease, if it's not primary focal segmental glomerulus gross, if it's not primary membranous nephropathy, or if it's diabetic nephropathy, or if it's amyloid nephropathy you have to treat the underlying cause.

So if it's secondary minimal change disease, secondary membranous nephropathy, secondary focal segmental glomerulosclerosis, and if it's diabetic nephropathy or amyloid nephropathy you have to treat the underlying cause. So in other words getting rid of NSAIDs, treating their infection, treating their Hodgkin's lymphoma, treating their hepatitis B, treating their hepatitis C, their syphilis, getting rid of the offending medications. treating their hiv telling them to stop doing heroin and also trying to control their sickle cells this one glycemic control using insulin if needed and this one depending upon the type of amyloidosis may require further like chemotherapy but that's the important thing is you have to treat The actual secondary cause, which is a little bit beyond, we can't go through every single one of these, but you have to treat the causes that we kind of highlighted.

What we can discuss, and is important to discuss, is if they have primary causes of nephrotic syndrome. In other words, we don't know why. It's likely genetic, it's likely some type of autoimmune component, but we just don't know why.

What are those? That is your primary minimal change disease, your primary focal segmental glomerulosclerosis, and your primary membranous nephropathy. So primary minimal change disease, primary membranous nephropathy, primary focal segmental glomerulosclerosis.

How do we treat these? All of them, you're going to start them off on steroids. So you're going to start steroids because you're going to try to suppress their immune response.

This one was a T-cell response. This one was some type of immune complex response. this one we don't even know how it forms. But steroids are going to be the first particular thing.

Now, here's what's really helpful in diagnostics of the therapeutics, if that makes sense. If they have a good response to the steroids, so let's put that here, a really good response, that's highly suggestive of minimal change disease. And often times you can avoid doing the biopsy.

That's why we don't always go to biopsy first. If there's a poor response to the steroids, guess who it likely is? It's your nasty primary ones that are in adults. Your primary member in a nephropathy or your focal segmental glomerulosclerosis.

So in these, what did I tell you? Was the scary thing, I don't put primary, focal segmental glomerulosclerosis. What did I tell you was a big thing with these that they cause that this one does not cause? These can cause end-stage renal disease. So if they do not respond to steroids and you don't treat them any further, guess what these suckers can do?

They can cause chronic kidney disease. So they can jack up those kidneys and lead to end-stage renal disease. Do we want... that?

No. So if steroids weren't working, what can I do to reduce the risk of these patients developing chronic kidney disease? Then I can put them on long-term.

And this is where we do the biopsy. So usually if you put a patient on steroids, they have a good response, it's likely minimal change. If they did not have a good response, it's likely these two, you probably should get a biopsy to confirm and then put them on long-term immunosuppressive therapy because you don't ever want to commit a patient to this if you don't really know.

And so this is where you would do things like long-term immunosuppressants. And there's so many of these, I'm just gonna mention the biggest ones. The biggest ones that you'd wanna be able to remember here is gonna be something called, so we use cyclophosphamide, this is a pretty good one. And another one is called tacrolimus. These are other types of immunosuppressants that have been shown to be pretty beneficial in these patient populations.

So again, think about long-term immunosuppressive therapy if they failed steroids to prevent the progression to chronic kidney disease. My friends, in this video, we covered nephrotic syndrome. I hope it made sense.

I hope that you guys enjoyed it. And as always, until next time.

Transcript for:Understanding Nephrotic Syndrome and Treatment

Transcript for:
Understanding Nephrotic Syndrome and Treatment