Acute Kidney Injury

Hey Future Doctors! Thanks for joining me on Spoonful of Sugar, a podcast made for medical students, by medical students, to help the medicine go down. My name is Rhea, I'm a student at Drexel University College of Medicine, and I will be your host today. Everybody knows the kind of person that works so hard, they work all the time, and they never complain, they don't say a thing, they just do their job, do what they're supposed to do, and they might get a little bit badgered now and then, but they don't really say anything. And then one day, something happens, it doesn't have to be much, but they just flip out, and they go nuts, they're like, oh my god, and all that pent up anger is just released. I really think the kidney is that person. Think about it. The kidney takes so many hits in an individual's lifetime, especially when we're managing diseases. We want imaging, we give someone contrast, damage is the kidney, we want to treat someone's pneumonia, we give them an antibiotic, that can damage the kidney, someone has arthritis, we give them NSAIDs, again, damage is the kidney, and so the kidney keeps taking these hits one at a time, and it doesn't really say anything, it's kind of silent, and then one day, all that damage just kind of builds up, and the kidney flips, okay, and what do I mean when I say the kidney flips? Well, it doesn't do its job, it doesn't maintain homeostasis, and we get an accumulation of urea and electrolytes, and that can be deadly. And so that's all I say, the kidney is that person, okay, the kidney is low key, crazy. So how do we handle a crazy person like the kidney? Well, we look out for them, we check in with them, we try to see if they're okay, and if they're not okay, then we try to figure out what's going on so that we can manage that, and that's exactly what we have to do for the kidney. In today's episode, we're going to talk about how we look out for the kidney in the setting of acute kidney injury. We are going to talk about how we monitor for kidney injury, the possible causes of kidney injury, and then dissect those a little further to talk about the pathophysiology. Like I said earlier, the kidney doesn't quite speak, okay, no one comes in with kidney pain the way they do with chest pain or confusion or signs of stroke. So we have to look out for the kidney, and to do that we use particular measurements, so it's really important to understand what measurements we use and why. So one of the ones that we use is creatinine. What is creatinine? creatinine is a breakdown product of creatine phosphate in the muscle, okay, so it's basically a protein product. So why do we use it? What does it tell us about the kidney? So creatinine is used as a surrogate measure for the glomerular filtration rate or the GFR. Do you guys know what the gold standard for GFR is? The gold standard for GFR is actually something called inulin, and inulin is a substance that's freely filtered by the glomerulus, and then after that it's not secreted or reabsorbed, and so that's why inulin gives us a perfect measure of the GFR. If we measure the inulin in the urine, then that should correlate really well to the GFR. Unfortunately though, inulin is difficult to measure clinically, and so we use creatinine as a surrogate. Do you know how well creatinine estimates GFR? It actually slightly overestimates. That's because a little bit of creatinine does get secreted by the tubules, and so because of that it's a slight overestimation of GFR, but it's the easiest thing to measure and it's kind of the best that we've got, and so that's why we use creatinine as a surrogate for GFR. Do you guys know what range of creatinine measure is about normal? If you're thinking that it kind of depends, you're absolutely right. The ideal range of creatinine depends on a person's muscle mass, so it tends to be higher in muscular people, it's higher in African-American individuals, and it actually tends to be lower in the elderly due to decreased muscle mass. But on average about 0.6 to 1.2 milligrams per deciliter, 0.6 to 1.2, that's considered about normal creatinine. But you have to remember that when you look at the creatinine, it's always relative, so it's important to look not only at a person's creatinine at that given time point, but also at previous time points to establish a person's baseline. So if a person's baseline creatinine is about 1.4, then when you see that number of 1.4, that shouldn't jump out to you. However, if that number suddenly becomes 3, at that point, it would be considered acute kidney injury. Another measurement besides creatinine that we use is something called blood urea nitrogen, or BUN. Do you guys know what BUN is? It's urea, and urea is a product of protein degradation, so it's actually made in the liver, and then it's secreted by the kidney. So that's urea. Do you guys know what BUN tells us? I think to understand BUN, you have to know what happens to urea in the kidney. So urea does get filtered in the glomerulus, and a lot of it is secreted in the urine. But most of it is actually reabsorbed, and the reason that it's reabsorbed is because remember how in the renal medulla, we have to reabsorb urea to set up a high osmolar gradient that helps concentrate urine later on. It's okay if all the details aren't crystal clear in your head right now, but just realize that urea is net reabsorbed by the kidney. However, if the kidney is damaged, then we can actually get too much BUN, and that leads to a condition of uremia. And uremia leads to a constellation of symptoms, including a cephalopathy, pericarditis, and all these symptoms are actually serious enough to warrant dialysis. So urea is complex in terms of how it's handled by the kidney, but too much BUN is bad. So do you guys know what normal BUN is? It's about 7 to 20 milligrams per deciliter. So if it rises too much above that, then you know that the kidney is not working well. So creatinine and BUN, these are the main tests of kidney function, and we can actually correlate them in a ratio. So we can use the BUN to creatinine ratio to see how well the kidney is working as well. There's a few other helpful measurements in the context of kidney injury, and we'll discuss these in more detail in the context of each type of kidney injury, but just keep these in the back of your minds. Some other measures that we do use are urine osmolality, which is measured in milli osmols per kilogram. We also use urine sodium concentration and milli equivalence per liter, and then we also use fractional excretion of sodium or phenol. It's Fe and A. This is a more complicated formula, but it basically relates sodium to creatinine, and it calculates a fraction of how much sodium is excreted. Don't worry about all of these values too much, or all these types of measurements, because when we go into the different types of acute kidney injury, we'll talk about what happens to each measurement, and I think it's easier to understand given some context. So that brings us to our discussion of the different types of kidney injury. Now it's important to realize that kidney injury can be either acute or chronic, so we are going to focus on acute injury, but it's important to realize that acute injury can still happen in somebody who has chronic kidney injury, and so in that case, it would be called acute on chronic kidney injury, or AKI on CKD. So how do we know if someone has chronic kidney disease? The easiest way is to just look at their creatinine. If their creatinine is just like riding in the threes or fours range, then you know that they have some baseline pathology, but it's always at that level, and so you know that it's not an acute injury. Now if that same person with baseline in the threes or fours comes in, suddenly with a creatinine of six, then you know that something's up, and you have to investigate it further. So how do we investigate acute kidney injury? How do we categorize it? We categorize it based on where the damage happens. So it can either be pre-renal happening before the kidney. It can be intrinsic renal, so happening within the kidney, or it can be post-renal happening somewhere after the kidney. And when I say before intrinsic and after, I'm talking about anatomically. So anatomically, where does it happen? I think the easiest one to understand is post-renal injury. So let's start with that. What happens in post-renal AKI? Post-renal is really just an outflow obstruction. So something downstream of the kidney gets obstructed and you end up with a backup of urine. What are some causes of this? Benign prostatic hypertrophy for sure, or even a prostatic tumor could could do this. A kidney stone that's large enough could cause obstruction. any other kind of tumor or even congenital abnormalities, like posterior urethral valves and little boys. So all of these things can obstruct the kidney and cause a backup of urine. Now all those measurements that I discussed earlier, they're not really worth memorizing for post renal injury and why is that? It's because usually the symptomatology and imaging can lead you to the right answer and a lot of times we start by ruling out post renal causes. Just to give you an example, what would you see on ultrasound if somebody had an outflow obstruction? You might see hydro nephrosis, so enlarged dilated tubules and calisies of the kidney because of that outflow obstruction and the kidney basically enlarges and you get hydro nephrosis. Further real nerds though who can't rest without knowing about these measurements, we're gonna go over them. So in post renal injury, like I said we have a backup of urine and so initially what's the kidney in a due? It starts reabsorbing whatever it can because it's like well there's no room forward so we might as well go back into the body and so what's gonna happen to be when the creatinine ratio? It's gonna increase, okay? Think of be when the creatinine is how much the body is reabsorbed because remember that usually the body does try to reabsorbed the urea and so be when the creatinine is gonna increase. What happens to the phenom? The fractional excretion of sodium? That's gonna decrease because you're reabsorbing more sodium, you're not excreting as much and so phenod decreases and be when the creatinine is gonna increase initially. Eventually though you get damaged to the tubules of the kidney from all that urine just building up there. Remember we have the hydrogen afrosis and you can imagine that starts wearing away at the tubules. So then what happens to the bu and creatinine ratio? It's gonna decrease because the kidney can no longer reabsorb. What's gonna happen to the phenom? It's gonna increase for the same reason. You're not able to reabsorb and so more sodium is getting dumped into the urine and so the biggest takeaway for post renal causes of AKI I think is just understanding that it's some kind of obstruction to urine outflow. The next type of AKI that I think is easiest to understand is pre renal injury. What happens in pre renal kidney injury? It usually results from decreased blood flow to the kidney. So what would cause that? What would cause decreased blood going to the kidney? Any type of volume depletion for sure? So for volume depletion think renal versus extra renal causes. Renal causes would be things like diuretics or osmotic diariesis and diabetes. Extra renal would be volume loss in other ways. So vomiting, diarrhea, if you have systemic burns, if you're bleeding a lot, those can all lead to volume depletion. What are other things that could cause decreased blood flow to the kidney besides volume depletion? So this is kind of tricky but you can get intravascular volume depletion. So what are some conditions where you might be fluid overloaded but there's actually decreased blood inside your vessels? Think about heart failure, liver failure, okay? They can cause edema, uh, sighties and so there's a lot of fluid in the body but it's not where it's supposed to be and so we're actually getting decreased blood flow, blood flow to the kidney anyway. Other causes of pre-renal injury? States of shock. So in like sepsis, neurogenic shock, anything that causes shock is causing it's it's an impairment of perfusion and so we're not getting adequate perfusion of the kidney either and so that can lead to AKI. And then pretty much anything that decreases blood flow to the kidney. The main things I want you to think of are systemic volume depletion as well as intravascular volume depletion and then think of states of shock. Now what happens to our measurements in pre-renal injury? So BUN to creatinine ratio? What would happen to that? Well in pre-renal, think do you want to absorb or do you want to excrete? In pre-renal kidney injury if we're not getting enough blood flow we probably want to reabsorb because the kidney things were volume depleted. And so it's going to absorb more and so the BUN to creatinine ratio is going to increase and now I'm going to start giving you some numbers because I think it's worth knowing. So the BUN to creatinine ratio in pre-renal AKI is actually over 20. What happens to FINA if we want to absorb or excrete? So we want to absorb and so the FINA is going to decrease and again a number the FINA is going to be less than 1% in pre-renal AKI. If you looked at the urine sodium, the urine sodium would be less than 20. So think low sodium in the urine. What would be the urine osmolality in pre-renal AKI? Again think are you absorbing or are you excreting? You're trying to absorb and so the urine is going to become concentrated and urine osmolality would be high like over 500 because we're reabsorbing the water and we're concentrating the urine. So BUN creatinine and urine osmolality are going to be high. The urine sodium or you can look at the FINA, those are going to be low. So the biggest takeaway from pre-renal injury is the causes so anything that causes decreased blood flow to the kidney and the outcome you're going to try and get more absorption and so BUN creatinine is going to rise. FINA is going to decrease and then finally we can talk about intrinsic renal injury. I saved this one for last because there's a few more details that I want to go over here. I'll just start by asking though what causes intrinsic renal injury? So the answer is actually several things and to understand those things I think we need to talk about the types of intrinsic renal injury. How do you guys think about intrinsic renal injury? I generally split it into where the damage is occurring. So it could be happening in the glomerulus, it could be happening in the tubules or it could be happening in the interstitium of the kidney. So glomerular diseases, we actually have an entire episode on the specifics of different glomerular diseases. So if you haven't haven't checked that out yet I would definitely recommend doing so. So I won't go over those in detail here but glomerular disease can cause intrinsic AKI, tubular disease. Do you guys know what the most common cause of intrinsic renal AKI is? It's also a type of tubular disease. So it's acute tubular necrosis, that's the most common cause of intrinsic renal AKI. And acute tubular necrosis or ATN is caused by ischemia or toxins to the kidney. And do you guys know the pathonomonic finding in the urine for ATN? It's those muddy brown granular casts. If you see those, you've got that question. It's acute tubular necrosis. And so we talked about the glomerulus, we talked about the tubules, and then we have the interstitium. So what's the disease that affects the interstitium of the kidney? I'm thinking about acute interstitial nephritis or AIN. And this is usually caused by drugs, it's kind of like a hypersensitivity reaction. Do you guys know the pathonomonic finding of AIN? It's a triad. So it's this triad of fever, rash, and it issinophilia, okay? Fever, rash, and issinophilia for AIN. Now in real life, this pathonomonic triad is only present in like 10% of cases. So you're usually not going to see the E issinophilia especially. But on the boards, they're usually going to give you all three things. The fever, the rash, and the E issinophilia. Now let's talk about measurements for intrinsic kidney disease. So what happens to BUN creatinine ratio? Think, are we absorbing or are we excreting? So in intrinsic renal injury, we're actually not able to absorb because we have damaged just some component. So usually the BUN creatinine ratio is going to be low, okay? Think less than 15. Remember in pre-renal, it was high. It was over 20. In intrinsic, the BUN creatinine is going to be low less than 15. What happens to the pheno? If you if you realize by now, it actually kind of does the opposite of what BUN creatinine does. So the pheno is actually going to be high. It's going to be over 2%. Do you remember what the pheno was in pre-renal injury? It was less than 1%. And so what is pheno in intrinsic renal injury? It's over 2%. And then the urine sodium is going to be high as well. It mimics the pheno. And so urine sodium is going to be over 40. What was the osmolality beam of the urine in intrinsic renal injury? Again, if you think we're not absorbing because we can't so we're excreted. The osmalality is actually going to be pretty low because the urine is going to be dilute because we are not reabsorbing. And so because we are not reabsorbing the electrolytes and remember that water follows the electrolytes. So if the electrolytes are in the urine, then the water is going to stay in the urine and that's why urine osmalality is going to be pretty low. It's going to be less than 350. So what I want you to take away from intrinsic renal injury is that we have damaged either the glomerulus, the tubules, or the interstitium. And we are not able to reabsorb because the kidney is not working. And so BUN creatinine is going to be low and FINA is going to be high. Now I do want to go into some more details about two specific diseases that we talked about just because they are very commonly tested. And so what did I say was the most common cause of intrinsic renal AKI, acute tubular necrosis. And this is really important to know because it's very common obviously because it's the most common cause of intrinsic renal AKI. So what were the causes of ATN? We said it can happen from ischemia or toxic injury. And so there are some important toxins that we need to know. For example, what if a patient gets a CT scan to look for, let's say a pancreatic tumor and we have a sudden rise in creatinine? That would be from contrast, okay? We can get contrast induced damage because we get contrast when we're getting images, especially for tumors. Now what if a patient gets a crush injury in an MVC and then their creatinine rises? So crush injury is important because it can result in the release of a lot of myoglobin. And myoglobin acts as a toxin to the kidney as well. So crush injury, rabbitomyolicis, they can both lead to acute tubular necrosis. Now what if a patient ingest antifreeze? So ethylene glycol can cause ATN. What else would you see in ethylene glycol ingestion? You'd see stones, right? What type of stones? Calcium oxalate good. Now it's important to know how ATN progresses, so the course of ATN. And ATN generally happens in three stages. So initially we have some kind of inciting event, okay? The contrast, the crush injury, the ethylene glycol, whatever. The second is the maintenance phase. So what does the patient look like during the maintenance phase? Well, the maintenance of ATN, you can imagine, is pretty bad, so the patient's not going to look that great. They're going to be oligiric. They're not making a lot of urine. They're going to be uremic. They're going to be hyperkalemic, because they're not making urine. And they're going to be in a state of metabolic acidosis, okay? So remember that it's important to know that in the maintenance phase of ATN, we're going to not be making a lot of urine. We're going to be hyperkalemic, and we're going to be having metabolic acidosis going on. So the third phase then is the recovery phase, so the opposite. What's going to happen in the recovery phase of ATN? We're polyuric. We're hypokalemic, okay? Because remember, before we were oligiric and we were hyperkalemic, in the recovery phase, we're now making more urine and we're losing that potassium. And then the creatinine is going to fall as well. So in healing, what we actually get is re-epithelialization of the tubules. Because remember, in acute tubular necrosis, we're getting literal necrosis of those tubules. And so the tubules are kind of falling into the epithelial cells or falling into the tubules, and that's what creates those money-brown casts. What we see on your analysis is the necrotic epithelial cells that are in the tubules, okay? So when ATN finally heals, we get re-epithelialization of those tubules. Wow, that's hard to say. So my follow-up question to you is when during the course of ATN is the patient most likely to die? Well, you think in that second maintenance phase, because that's when I said things were bad, right? Not making urine, hyperkalemic, metabolic acidosis. The maintenance phase is really when the patient is most at risk of death in ATN. Now, our next disease, the second one we talked about, was acute interstitial nephritis. You might also hear acute tubulointerstitial nephritis, but I generally just call it AIN. So what was the triad of symptoms that we saw in AIN? Fever, rash, and eosinophilia. You might see in eosinophiles in the urine as well. That would be eosinophiliauria. So remember, fever, rash, eosinophilia for AIN. And then, what was the cause of AIN? It was an allergic response to particular drugs. So diuretics can cause this. N-sets can cause this. Antibiotics, especially like penicillin, cephalosporins, and even ciprafloxicin, they can cause AIN. And then, another antibiotic is refampin, used for TB. And then, proton pump inhibitors, like a meprosol, they can cause AIN. So just to quickly summarize everything that we've gone over in this episode. AKI, or acute kidney injury, is defined as a sudden rise in creatinine in a 24-48-hour period. And it's important to look at a person's baseline creatinine to know that that creatinine rose acutely. So it can occur on a background of chronic kidney disease, and so you have to look at the baseline creatinine. Another thing that I forgot to mention this earlier is that it's possible to find decreased urine output in the setting of AKI as well. Like, especially if you have some kind of obstruction, you'd have decreased urine output. If you have decreased blood flow, you'd have decreased urine output. So it's not necessary, but it can happen in AKI as well. The biggest thing you're going to look at, though, especially on the exam, is the patient's creatinine. Now, from there, we need to combine their history with labs to figure out why the patient has AKI. So if you get a history about an elderly man with a history of decreased urine stream, what do you think is going on? He probably has benign prosthetic hypertrophy, and so he probably has an outflow obstruction, and he probably has post-renal AKI. What about a two-day old male who isn't making any urine? In this person, I'd probably think about posterior urethral valves, and so that would also be post-renal AKI. You can often rule out post-renal with imaging, and what do we see on ultrasound if someone has outflow obstruction, hydro nephrosis? Now, what if the BUN creatinine ratio is high? The phenol is low, and the urine osmolality is high. I'll repeat that. The BUN creatinine is high, the phenol is low, and the urine osmolality is high. What type of injury is that? I'm thinking pre-renal, because it looks like we're trying to reabsorb stuff, and so causes of pre-renal are decreased blood flow. That can be from depleted volume, total volume, so like peeing, bleeding, vomiting, diarrhea. It can be from decreased intravascular volume, as in cirrhosis or heart failure, or it can just be from decreased blood flow to the kidney, like in sepsis or shock. Now, what if I switch all those and say the BUN creatinine is low, the phenol is high, and the urine osmolality is low? Again, BUN creatinine is low, phenol is high, and urine osmolality is low. That's intrinsic renal, okay? Because we're not able to reabsorb, and so everything gets excreted. Now, muddy brown granular casts is pathonomonic four, acute tubular necrosis, very good. Recent treatment with antibiotics, and now the patient has fever, rash, eosinophils, that's pathonomonic four, acute interstitial nephritis. So, thanks guys for playing along with that little summary review. The moral of this story is, don't forget about the kidney, it's very sensitive, and so we always want to look out for it and check in with it. Okay, look at the creatinine and the BUN and compare the values to the baseline. I hope that this wasn't groundbreaking information, but I do think that sometimes it just helps to review things differently, or from a fresh perspective. If you guys really want to drive the message home and solidify AKI, I challenge you to explain what we just went over in this episode to somebody. Anybody, it can be your dog for all I care, or you can say it for yourself out loud in the car. Just try to give a five minute recap of what you learned and really solidify everything we went over in this episode. You don't have to, of course, that it's just a suggestion. So, thank you so much for your time, guys. I definitely hope that you guys enjoyed this episode. that this was helpful to you. If you have any questions, concerns, comments, please log on to spoonfulofsugar.org and you can post them under this episode. And we would love if you would subscribe to our podcast, give us a rating or a review. The kidney is definitely a very complex organ, makes me go SOS, but hopefully one episode at a time, spoonful of sugar can help the medicine go down. (upbeat music)