Another one of my topics, which will get heavily tested on this exam of yours. But in reality, this is the centerpiece of your clinical practice. As we all know, kidney dysfunction is the center of the universe. Jen, I liked the defibritide trivia. Other drug name trivia, which is great. Everyone knows Lasix. Do you guys know why warfarin is called warfarin? No. It's on some of my research foundation. Explain. Oh, that's all I know. Does anyone know the story? Dr. Zimmerman? Dr. Karl Paul Link was investigating the cause of dairy cow hemorrhage. And he found out that they were eating moldy hay, and this mold made warfarin. And he isolated it, and it was the first anticoagulant. The University of Wisconsin made big money on that. Yeah, so he actually had a farm with cows that were dying. And he was trying to figure out why they died. And he was in Minnesota at the time, went to Wisconsin. And one of his graduate students, that was the graduate student's thesis, is to figure out why his dairy cows were dying. And the funding for that project came from the Wisconsin Alumni Research Fund. So there you go. That's good trivia. Premarin is another good example that we use. So anyway. OK, AKI, kidney support therapy. There are probably three concepts in this talk that will get tested on. Although, I will say again, as people in this room are also doing work on this, those of us in the field, as we put more and more data out there, this will become more integrated into your exam and testable materials. As always, one of the crucial parts of the exam, when you get a STEM question, and this concept is being tested, it's going to look like sepsis. That's it. It's going to look like sepsis. And the question will rely on you understanding, are they asking me something about kidney injury and kidney support therapy? These are actually relevant disclosures to this talk, because these companies are related to kidney dysfunction and renal support therapies. The key points to take away is recognizing the multifactorial drivers of the AKI syndrome. So this is actually really important, because Scott mentioned this yesterday, that sepsis is an umbrella term. And it's actually a reaction and not a diagnosis. And AKI is the same. AKI, as we study it more and more, is a reaction to what's happening and not exactly a diagnosis. We have to understand what our opportunities for management are, and then understand the salient points currently for kidney support therapy. So this won't be a testable question, but one of the things that we should recognize more and more is that the ubiquity of kidney injury per our current diagnostic constructs. So if we think about creatinine changes or urine output changes, one out of every four patients that you admit to your ICU, regardless of cause of disease, cause of being in the ICU, whether they have a trach and a hangnail, or if they have a TBI, or if they're an on-patient who's septic, doesn't matter. Doesn't matter. One out of four kids will have AKI, and those patients do worse, independent of severity of illness. What I'm showing you here are a sequence of manuscripts that are large data sets from the newborn period through the pediatric phase to the young adults to adults that are the kind of flagpoles in AKI epidemiology, as it were, at present. And what we know, again, is that the signal is the same across all populations. About 25% of patients have some form of AKI, and more AKI associated with more death. What we are learning more and more is, and this is actually one of Dr. Tasker's priorities for PCCM, is to think more globally about data that comes from other parts of the world, and not just Uber megacenters in the US. So a couple of Canadian groups have done a lot of good work. A couple of the groups in Southeast Asia have done a lot of good work. And in Saudi Arabia, to be clear, looking at global epidemiologic signals of AKI. And you can see here in this paper, this is an adult data set, honestly, but this is mirrored in kids, and AKI is everywhere if we look at the disease epidemiology itself. On the test, what will be asked is either if the disease process, if creatinine elevation and urine output changes are a intrinsic kidney process, or if they're indirect, attributable to sepsis, or some other process. So that in and of itself is part of the stem to understand, because the answer that will come out will either be to address something directly related to kidney function, or deal with the problem, deal with the sepsis, stop, get the hammer out of the kid's head, whatever it is, that's the problem that you have to deal with. That will become clear if you are paying attention to the stem of the question. So per the definition at present, AKI in the acute phase is defined as less than seven days, although per some of our diagnostic guidelines, it's now becoming clear that 48 hours as the kind of cut point for AKI, versus 48 hours to seven days, is a different process altogether. And this is also mirrored in sepsis with early injury and extension injury. But it's a decline of renal function as manifest by impaired creatinine clearance, and currently we use GFR. One of the things that adult ICU docs don't even think about are the effects of muscle mass, age separated by a couple of years, protein intake, nutritional status, catabolic state, and actually fluid balance. Because the data about fluid corrected serum creatinine is now becoming more and more common, and we do think about that. For the purposes of just generic diagnoses, everyone is pretty familiar with AKI as it's broken into these three pretty prehistoric classifications of AKI. There's pre-renal or not so bad AKI, there's renal or intrinsic or kind of bad AKI, and then post-renal or obstructive AKI. Now, for the purposes of the exam, what is probably the clearest way to think about this is that sepsis-related stems will go primarily into that reduced renal blood flow category. Whereas when you get a question that's related to intrinsic AKI affecting the glomerulus or tubular interstitium, it's not going to be necessarily about sepsis. The question will probably be about nephrotoxins and adjudicating those meds. And this gets into that 48-hour time point, this gets into the duration of injury. But almost invariably, there's never a question on post-obstructive AKI, but the first two will be delineated in the stem of the question. The diagnostic criteria you should know. So in this table, this is the KDGO operating definition for AKI. But we in pediatrics look at the serum creatinine change and the urine output change per different cutoffs. What I've showed over there on the right are the kind of newer, even though they're not that new, different specific biomarkers specific to tubular injury, glomerular injury, mesenchymal injury that we're trying to integrate. Now, what we are actually doing more kind of currently is trying to integrate the podium definition. So the podium consensus group, when we kind of talked about modifying what was existing for kidney injury and dysfunction, the modifications happen through the definition of initiation of RRT and inclusion of fluid overload percentage. So this, again, this is probably testable. I have not seen a question on this, but given now the widespread readership or widespread at least distribution of the podium criteria across all the different areas which podium tackled, this is fair game. So just thinking about the diagnostic criteria as it was published in the podium collaborative will be important for you. In your relevant practice, this is the most important vital sign that we have. Do not simply flush it down the toilet. And this is, again, part of my soapbox, but it is true. And part of it is because the classification of AKI could occur in the stem of the question that the creatinine may not be different. And that intuitively makes sense to us because we understand how volume of distribution to the conversation we had earlier could affect a substrate like creatinine, which is milligrams per deciliter or millimoles per liter. So it's corrected. But urine output is part of the classification criteria. So you could get a question that makes you analyze the stage of AKI or the presence of AKI by urine output alone. In practice, this is one of those things that we should be thinking about because if you classify AKI by creatinine alone, you don't get the full story. We did a series of derivation studies looking at creatinine and urine output thresholds in our AWARE dataset. And these are published in PCCM a couple of times looking at severity of illness and illness overall if you just use creatinine, just use urine output or both. So I show you this for clinical practice, but I show you this just as a holistic measure and also because this could show up on your STEM, like in the paragraph of the question. Here are some formulae that are good to know. So GFR, the Schwartz formula and the modified Schwartz, which actually integrates this K factor, this constant factor. It's unlikely to be clear that you will be asked to calculate a GFR. It is much more likely that you will be asked, you know, be able or be made to interpret a first level delineation of the source of AKI in the clinical history. Be mindful, be looking for the history of dehydration. Make sure you pay attention to the metabolic panel, specifically what is there and what is not there. Going back to a previous conversation, if they mention ammonia, the answer's not going to be about kidney function. It sounds dumb, but these are the things that stand out. Like if you get a metabolic panel and all of a sudden they put an ammonia in there, you may be thinking, well, clearly the creatinine's, It's not about, the answer's not gonna be related to kidney function. But if they don't mention ammonia, it's like a tip off the other way, okay? So just be thinking about that. Urinalysis and microscopic analysis, if it's shown, is meant to give you a sense that they're looking at intrinsic kidney dysfunction. Casts in the urine, blood in the urine, they're not asking about sepsis. They being me. Okay, they being us, when we are asking these questions to you, the urinalysis is a crucial piece because who asks for urinalysis? Nephrologists, right? Right, we flush the urine down the toilet. No, no, no, we can do better too as intensivists to do this. But the reason is because you should be thinking about, that's what they want you to think about, primary kidney versus not, indirect kidney. Excuse me. There is a height-based integration for GFR. I mentioned the plus minus of FINA before. But again, just pay attention. If they give you information, such as enough data to calculate a FINA, it's not about sepsis, okay? Third level, compliment is a good tip-off. If they start mentioning compliment, it's probably related to something that Dr. Mazynski just talked about. So little tip-offs in the STEM will give you a hint on what's being asked. In our management, this gets back to kind of the supporting care and the options. The answer in relation to what we can do in practice, and this is borne out because of repeated data from the NINJA Collaborative, the NINJA-AKA Collaborative to reduce nephrotoxin exposure. Nephrotoxic medication adjudication, again, from our smartest people on the team, the pharmacists, helping us with this, is going to be a very high-priority answer if it's related to AKI. So be mindful of that, because that's, without a doubt, something that is doable, something that is repeatedly shown to reduce exposure, incidence, and severity of AKI. So this AKI bundle is actually from the UK. It's not something that we have readily integrated into practice, but hope springs eternal that we will start doing this. Timing, initiation, and other factors for renal replacement therapy. So yes, we have the AEIOU mnemonics. Yes, we have all this stuff about it. We also, in our journal clubs, repeatedly make the mistake of extrapolating adult CRRT initiation trial data as if it has bearing, you know, relevance into our practice. So if you look, and do you guys remember talking about the RRT initiation trials recently, START-AKI or AKIKI, anybody talk about these? No one, whoa, okay. Anyway, hold on, let me stagger back from this. So there are these really large initiation trials, timing of initiation trials for renal replacement therapy in adults. What has been shown is nothing. They all conflict with each other. However, the triggers for RRT initiation in adult world, because they don't really examine their patients all that often, is creatinine. We, because we are actual clinicians and we examine our children over and over again, rely on hydration status, urine output, and fluid accumulation. So our most common indication, as everyone in this room will nod their head to, is fluid, is okay, not enough's coming out and you're swelling up. That is our indication. It is not really about creatinine. It is not about ingestions, though certainly we have our indications for things like in lithium and other drug toxicity, hyperammonemia being one of the newborn ones. So what do you need to know about CRRT? There's a spectrum that exists. The most common form of renal replacement therapy in the world is PD, by far, by far. PD is by far the primary form. Will you be asked a question about PD? No, because most of the time, PD is an outpatient practice and nephrologists guide it. In the inpatient setting, how many of you have ever placed a tank-off catheter yourself? Okay, yeah, but you don't count. You don't count. You count for a lot of things. But no, so in the pericardiac surgery population, those of you who work at centers where PD catheters are prophylactically placed, I'm looking at my Cincinnati friends, I mean, there are centers that do prophylactically place them, although it's not PD, it's just passive drainage is being used most of the time. We're not gonna be asked that much about PD. That being said, you should know the mechanistics of PD related to glucose concentration, dwell time to help fluid removal, right? For CRT, which is more of our cup of tea, as it were, the spectrum now has kind of included more and more PERT, or prolonged intermittent renal replacement therapy brought along expeditiously by COVID and the need to have kind of intermittent breaks and things like that. But just know that this is the spectrum, just simply from a mechanistic process, my analogy and other people use this too, is coffee and tea. Have you guys heard the coffee and tea analogies of? Okay, so who likes to drink coffee? Good, who likes to drink tea? Okay, to really understand CRT, you only need to know those two things. Coffee, how do you make coffee other than pressing the button on your Keurig? Pressure, pressure and fluid, French press coffee, push down hard, put a lot of hydrostatic pressure on there relies on convection. Convection relies on the physics principle of osmotic drag. And what convection is very, very good at, or for, is for the purposes of, you know, large middle molecule clearance. Tea, on the other hand, how do you make tea? Bag, put it in water, diffusion across, that is based on a concentration gradient. So diffusion and osmotic drag, solute drag, are the two principles involved in CRT. Diffusion is good for middle, you know, middle low molecular weight. Convection is also good for kind of middle molecular weight more than the low molecular weight. So tea up on the top right, coffee on the bottom left. And those are the two things that go to make up your CRT. And when you look at clearance, clearance is actually something that is testable material. And the main question that's asked is related to protein binding and size of something. Does it come off when you use kidney support therapy? Well, it's important to know that most of the stuff in our bloodstream is less than a couple thousand, you know, a couple thousand Daltons, or, you know, one to two kilodaltons of molecular weight. So diffusive clearance is pretty good for those. That's that kind of concentration gradient based thing. And then if we want things that are bigger, glucose and other kind of middle, low, middle molecular weight substances, we use convective clearance. Here are most of the setups that we use in pediatrics. The majority of our setup is actually CVVHDF. So if you have the big green machines, or now the Prismaxes are not necessarily green, but Prismaflex was green. Some people use Versenius and these other companies. It doesn't matter, right? The principles are the same. So starting with slow continuous ultrafiltration. So this happens in the cardiac OR. Modified ultrafiltration is an example of this. You basically put blood in, put it across a filter. The P out of the machine is the effluent. That's the ultrafiltrate. If you add fluid into the circuit itself, excuse me, if you add ultrafiltrate fluid, you're increasing the pressure on the filter. That's hydrostatic pressure. What does that sound like? It sounds like a French press. That is convection. That's called hemofiltration. When you add a counter-current mechanism of fluid, so those bags underneath the machine, those are scales. So the more bags you have, the more letters that go after CVVH. So CVVH is different than CVHD is different than HDF. There are four bags for HDF because you're looking at pre-replacement, post-replacement, the effluent, and the dialytic fluid. That's why there are four bags. One happens to be yellow. Make sure it's yellow. So the HDF part of it is when you mix everything together. You have replacement fluid that increases the pressure along the filter. You have post-replacement fluid that prevents dehydration of the blood because as you pull fluid out and it goes along the filter, the blood gets hemoconcentrated. So you don't want the blood to get clotted in the line. So that's why you add more fluid. And then you add dialysis fluid. The most common electrolyte abnormalities is a testable thing. Hypocalcemia is one, and it's not necessarily because of citrate, although everyone thinks it is. Because the most common anticoagulation solution we use in the US is citrate, which is just like EDTA in blood. We talked about what blood is stored in and why calcium is low. Calcium actually goes down because you don't use calcium in the dialytic fluid. So you're bathing against zero. So that makes sense. So calcium comes out. The other one is hypophosphatemia. So, you know, the adult world has started to use more phos-replating replacement solutions. We've been slow to adopt them. Don't forget about those two, okay? So if you have a patient in the stem of the question who's on CRT and they mention phosphorus or they mention calcium, it's intentional, okay? It's not random. Those two things don't generally show up if you're thinking about sepsis, if you're thinking about something else, just pay attention to those, okay? All right, so this goes back to kind of convection and diffusion. And here's your practical consideration. Hemodynamic stability is paramount for us. Somebody who goes on circuit now, as recently as 10 to 15 years ago, you could not start a CRT circuit without a physician being present, an ICU physician armed with all sorts of vasoactive substances in pocket and ready for a crash. That has now gone away. The reason it's gone away is because we have recognized bradykinin release syndrome. And bradykinin release syndrome is specific to the filter. It's pH sensitive. So what's happening, if you guys aren't prepping the CRT circuit and the nephrology team is or your primer team is, what they're doing is prepping the circuit so it's pH controlled. You should be mindful of the pH of the patient. As long as everything's above seven three, you will not see bradykinin release. So somebody who has massive hemodynamic instability on initiation could be related to volume and distribution of vasoactive support that's going on, but it's not from something else. Those are usually transient dips. It's not from volume loss. It's not because there's blood coming out of the machine or whatever. So the hemodynamic stability is a big point. Access is not a question that comes up, but for your purposes, access is success. So be mindful that small babies can take eight French catheters in the neck. Anticoagulation, we generally use citrate, which is ACDA, but other protocols have come along, including prostacyclin, BiVal and other anti-platelet agents in maintenance. Maintenance is kind of continued partnerships with nephrology, be thinking about filter support. And then again, for the purposes of the kind of test-taking aspect, really be thinking about the progress or lack thereof of the patient's primary disease process. If the patient is on CRRT, it's generally not going to be a question that's primary kidney disease. It's going to be secondary to another process. So if there ever is a question about, is this patient ready to be taken off of CRRT, your answer is going to be related to, not the kidney function, but is the primary disease process any better? Does that make sense? Okay, good. So again, this is actually a carryover slide. So I think that's it for me, so. Wow, thank you. Yeah. Thank you.

immunocompromised children

solid organ transplants

stem cell transplants

immune suppressants

infectious diseases

multidisciplinary approach

acute kidney injury

kidney support therapies

urine output diagnosis

citrate anticoagulation

KDIGO criteria

nephrotoxin management