Welcome to the Multi-Professional Critical Care Review Course, Pediatrics. Welcome. This is the Society of Critical Care Medicine MCCR Pediatrics Acute Renal Failure and Renal Replacement Therapy lecture. My name is Nick Ettinger. I'm an assistant professor in pediatric critical care at Texas Children's Hospital, Baylor College of Medicine in Houston, Texas. The objectives for today are to understand the etiologies of and plan treatment for patients with acute renal failure or acute kidney injury, and to understand the indications, modalities, and complications of renal replacement therapy. So let's start with a case. This was a previously healthy 10-year-old African-American female who had a history of slipped capital femoral epiphysis, or SCFI, and she had developed avascular necrosis of her left hip, secondary to her SCFI. So the operation she underwent was a left hip fusion, and preoperatively, her hematocrit was 38%. During the operative case, she had an estimated blood loss of 3.6 liters. She was transfused with 1 liter of PRBCs, and she received 5,200 cc's of crystalloid, 400 cc's of colloid, and postoperatively, her hematocrit was noted to be 29. On post-op day number one, she was in the ICU, in the PICU, and she was febrile. She had mild tachycardia, but overall was stable, and so ended up being transferred to the floor. And subsequently, on post-op day two through day five, she was febrile each of those days, and was transfused with two units of PRBCs on post-op day number five, due to anemia. On post-op day number seven, she went back to the operating room for an incision and drainage due to her continued fevers, and the intraoperative cultures that were obtained grew E. coli and protease, and so she was placed on broad-spectrum antibiotics with vancomycin and piperacil and tezobactam, and her repeat hematocrit at that point was 22. On post-op day eight, she again went back to the operating room for a repeat incision and drainage. Her hematocrit was 24. And then again, on post-op day 10, she went back to the OR one more time for another incision and drainage. Then after that OR trip, post-operatively, she was noted to have a large decrease in her urine output. She initially had 1.4 cc per kg per hour for the first 13 hours of that day, but then subsequently over the next eight hours, had only 50 milliliters of urine for those eight hours. On post-op day 11, her hematocrit was low at 18. Her creatinine had increased through 3.9 milligrams per deciliter. And then again, on post-op day 12, a repeat creatinine show that her creatinine had continued to rise to 5.04 milligrams per deciliter, and a vancomycin trough, which had been obtained on that day, showed a vancomycin trough of 244 milligrams per deciliter. And so she was emergently transferred to the PICU and underwent urgent placement of a dialysis catheter for intermittent hemodialysis. So the question is, what are the etiologies of this child's acute kidney injury? Classically, we think of three main etiologies for acute kidney injury. Prerenal causes, which are due to any reduced renal blood flow source, so hypovolemia, hypotension, or hemorrhage. Renal or intrinsic causes, which are due to any type of pathology that affects the glomerulus, the tubules, or the interstitium directly. This can be ischemia. This can be acute tubular necrosis. This can be HUS, glomerular nephritis, acute interstitial nephritis, or direct nephrotoxins. And then lastly, post-renal or obstructive causes of acute kidney injury, which are typically things like renal stones, a tumor, trauma, or posterior urethral valves. So what exactly is glomerular filtration rate? GFR is how much of a bloodborne substance can be excreted by the kidneys per unit time. As blood passes through the capillaries, the plasma portion of blood is filtered through the glomerular capillary walls and glomerular basement membrane, and now becomes ultrafiltrate and is now cell-free. And it sits in Bowman space, and it contains all the same substances that were in plasma — electrolytes, glucose, phosphate, urea, creatinine, peptides, small proteins. And then as that ultrafiltrate travels down through the tubules and the nephron, it undergoes tightly regulated secretion and absorption and becomes urine at the other end. So how exactly do we measure GFR? The gold standard of measurement of GFR is via inulin or iohexol clearance. And this is a substance that is freely filtered by the glomerulus and is not secreted and not reabsorbed by the tubules. And therefore the urine content, the amount that's actually in the urine, is directly related to how much was in the serum itself. However, in real life, we don't follow inulin, we follow serum creatinine. And serum creatinine is also something that is freely filtered and has a fairly steady-state body production, primarily from muscle. And its excretion is primarily due to filtration, because there is also a little bit of secretion that happens as well. And so therefore serum creatinine is only an estimate of GFR in the steady state. Typical GFR measurements are 100 to 125 milliliters per minute per 1.73 meters squared for any child older than a toddler. For infants, GFR is much lower, somewhere between 10 to 40 milliliters per minute. And just a comparison for numbers, your typical cardiac index for a normal healthy child is somewhere between 2,500 to 4,000 milliliters per minute per meter squared. What about renal vascular regulation and GFR? So both the afferent and efferent arterioles are under differential regulation. If the renal blood flow is decreased, then constriction of both afferent and efferent arterioles does not increase GFR. However, if you dilate the afferent arteriole while constricting the efferent arteriole, then this will increase GFR. And so the body will simultaneously in real life employ both constrictors and dilators simultaneously to try and increase and control GFR. However, the danger is that vasoconstriction can potentially reduce renal blood flow to the tubular epithelium, which is very blood flow sensitive, which can then damage that epithelium and lead to apoptosis and sloughing, which in and of itself can decrease GFR. And so below are listed various vasoconstrictors and vasodilators that affect the kidney. This is a cartoon that tries to summarize multiple different elements of how tubular reabsorption works and displays where the action of multiple different classes of diuretics work and where most of amino acids, glucose, bicarb, and water are reabsorbed and modified along the kidney, along with the effects of several different hormones. So how do we classify acute kidney injury? According to the 2012 Pediatric CADEGO criteria, there are stage 1, 2, and 3 acute kidney injury, and those stage 1, 2, and 3 have a serum creatinine component and a urine output component. If the serum creatinine is increased by less than twice baseline or more than 0.3 milligrams per deciliter and urine output has been less than 0.5 milliliters per kilo per hour for 6 to 12 hours, this is stage 1. For stage 2, that involves a serum creatinine increase between 2 to 3 times baseline with a decrease in urine output for greater than 12 hours. And stage 3 involves an increase in serum creatinine more than 3 times baseline or the need for any type of continuous renal replacement therapy, which we'll talk more about later, along with a decrease in urine output to less than 0.5 milliliters per kilo per hour for greater than a day or anuria that has been occurring for greater than 12 hours. Chronic kidney disease is defined as persistent AKI with loss of kidney function over a month, and then end-stage renal disease is somewhere between chronic kidney disease that's been occurring for somewhere between 3 to 6 months. So for an example, a typical septic term infant who gets placed on ampicillin and gentamicin, who has an admission serum creatinine of 0.2, but then by day 4, because nobody's been paying attention, has a serum creatinine of 0.8, that child has progressed to AKI stage 3. Even though a creatinine of 0.8 doesn't seem to be that high, that's a serious kidney injury. More recently, the Podium Consensus Conference, which is the Pediatric Organ Dysfunction Information Update Mandate, a consensus collaborative, developed consensus criteria for renal dysfunction from all organs, but for renal dysfunction as well in critically ill children. And they included several different criterions for dysfunction with some suggested thresholds and conditions. So for urine output, similar to the K-DIGO criteria, a combination of serum creatinine less than twice baseline or an increase greater than 0.3 with a urine output drop of less than 0.5 cc per kg per hour for more than 6 hours. In terms of actual GFR change, a GFR change to less than 35 mL per minute per 1.73 m2 was suggested as a threshold for renal dysfunction, although that excludes children less than 30 days because their native GFR may be that low. They also added initiation of renal replacement therapy for any cause with the exception of toxic ingestions or hyperammonemia as the etiology for the need for continuous renal replacement therapy. And then lastly, which we'll talk more a little bit about later, fluid overload with a threshold of more than 20% of fluid overload starting at 48 hours after ICU admission as a threshold for renal dysfunction. So why do we care about acute kidney injury? Why is it important? Well, it's common, and we know that it affects outcomes. So this is some data from several different review papers showing that in critically ill children generally, it's common somewhere between 10 to 82%, one in four patients, with a mortality percentage of 11% simply from AKI. Especially in children undergoing cardiac surgery, it's also common one to two to one in three patients with a 6% mortality rate. And then specifically from looking at what are the mortality likelihood ratios as your acute kidney injury increases, regardless of what classification scheme you use, KDGO or the older P-Rifle or the Akin criteria, with all of those criteria, as you increase your kidney injury from stage one to stage two to stage three, then your mortality likelihood ratio increases dramatically. So how do we evaluate the extent of acute kidney injury in a patient? Well, first level testing includes, number one, getting a good clinical history, and especially is there any history of dehydration or blood loss, anything like that, hypovolemia. A basic metabolic panel with electrolytes, BUN, and creatinine is important, as is obtaining a urine analysis and especially a urine microscopy evaluation, especially looking for eosinophils. It's important to have an assessment of the patient's volume status and urine output, and you need to get a height. And the reason you need to get a height is you need a height to estimate what the GFR for that patient should be or could be using the Schwartz formula, which has a constant times the height divided by the serum creatinine with the different constants shown there. In terms of a second level evaluation of acute kidney injury, this would involve calculating a fractional excretion of sodium, a FINA, which requires concomitant serum sodium, serum creatinine, as well as urine sodium and urine creatinine. If the patient has been on diuretics, you can do a similar calculation called a fractional excretion of urea, as well as looking at a blood smear to look at the morphology of red blood cells. So here's the formula for FINA, which is urine sodium divided by urine creatinine divided by serum creatinine, serum sodium divided by serum creatinine. And then similarly, the calculation for Fe urea is below. And then the different thresholds for assessing whether the cause is pre-renal, intrinsic, or post-renal are listed below. Lastly, if those studies are not able to help you figure out what the cause of the AKI is, then things like a renal ultrasound, a CBC with differential and complement levels can be helpful as well. So here's a practice problem. So a 50-kilogram child makes 75 mils per hour of urine. And using the following lab values, calculate, number one, an estimate of the patient's creatinine clearance, and number two, calculate whether are the lab values consistent with a pre-renal, intrinsic, or post-renal etiology for this child's AKI. So the answer is, for number one, to calculate an estimate of the patient's creatinine clearance, that would be the urine creatinine times the urine volume per minute, which would be 1.25 mils per per minute, divided by the serum creatinine, which was 2.5. And so you end up with 1.25 divided by the serum creatinine, which was 2.5. And so you end up with 30 mils per minute. And then are these lab values consistent with a pre-renal, intrinsic, or post-renal etiology? If you calculate AFINA, you end up with 3.5%, which is consistent with an intrinsic etiology for the child's AKI. What is the kidney version of troponin I? So in heart acute cardiac injury, we can use troponins to help guide our therapy and guide how worried we are about the state of the heart. And there is an ongoing search for an analogous marker for the kidneys. Serum creatinine is the most commonly used, but there are several other markers that have been investigated to help guide the therapy. And that are out there. Cystatin C, N-gal, KIM, and liver fatty acid binding protein. Of these, cystatin C is probably the most established. And there is a specific formula that you can use. And there's a website listed there to help you translate from an actual cystatin C value to an estimated GFR. And is a little bit more stable in a patient with unstable renal function, where the creatinine may vary quite a bit, a cystatin C tends to be a little more consistent and stable. So what about pathophysiology of acute kidney injury at a cellular level? So cellular pathogenesis of AKI is multifaceted and is thought to have two main components, a microvascular component and a tubular component. So the microvascular mechanisms, whatever the actual proximal cause is, involve both an increase in vasoconstriction that can happen from a variety of soluble mediators that cause a decrease in GFR, along with a decrease in vasodilation, which again, can happen from a variety of soluble mediators, again, causing a decrease in GFR. Those changes can also cause impairment of vascular smooth muscle cells and of endothelial cells, which can, that damage can lead to increased white blood cell and endothelial adhesion, which can also cause vascular obstruction, changing renal blood flow, again, leading to a decrease in renal GFR. In terms of tubular mechanisms, whatever the proximal cause may be, and there are multiple, then those lead to cytoskeletal breakdown of the tubular cells and loss of polarity of those tubular cells, which then can lead to apoptosis and or necrosis of those tubular cells and lead to sloughing of those cells into the tubular lumen itself. That can cause tubular obstruction, as well as allowing for leak via the basement membrane, and all of those causes together can, again, reduce renal GFR, as well as they can lead to release of inflammatory mediators that can act locally to worsen or exacerbate the microvascular mechanisms that were mentioned above. And there's a citation at the bottom if you want to read a little more detail. So, again, coming back to the clinical etiologies of acute kidney injury, we have pre-renal, we have renal, and we have post-renal. So, focusing first on pre-renal causes, this relates to hypovolemia, hemorrhage, hypotension, any source of decreased renal blood flow. What drives the formation of urine? So, here's a cartoon of the glomerulus with an afferent arteriole and an efferent arteriole. So, that typically in a normal healthy person, the mean glomerular capillary pressure in those capillaries inside the glomerulus is about 60 millimeters of mercury. Opposing that outward pressure from the capillaries is the intracapsular hydrostatic pressure, which is measured to be about 18 millimeters of mercury. So, that leads to a net pressure across the capillaries into the Bowman space of 42 millimeters of mercury of hydrostatic pressure. Then that 42 millimeters of mercury of hydrostatic pressure is opposed by a net colloid pressure within the capillaries of about 32 millimeters of mercury, because all the proteins are excluded from getting into the ultrafiltrate. Ultimately, leaving about 10 millimeters of mercury pressure, driving pressure, to form the ultrafiltrate, to form the beginnings of what becomes urine. And so, in other words, adequate blood pressure, because the only modifiable factor there is the glomerular capillary pressure, by regulation of the afferent and efferent arterioles, adequate blood pressure is key to normal kidney function, and is also key to appropriate delivery of oxygen for the kidney itself. What about renal intrinsic causes of acute kidney injury? So, what about drug-induced acute interstitial nephritis? Here, the classical presentation is dependent on a good history, and the classic presentation includes fever, rash, potentially eosinophilia with renal insufficiency, in other words, an increase in serum creatinine and a decrease in urine output. But there may not be, often there may not be any sensitive or specific signs or symptoms, other than you have a non-oligarchic rising BUN and creatinine in a patient who may have some arthralgias and arthritis, or may have some myalgia or myositis. Also, leading to confusion, this can be up to 7 to 10 days post-exposure to whatever drug is causing the problem. To evaluate for drug-induced acute interstitial nephritis, consider a basic metabolic profile, potentially a complete metabolic profile. A urine analysis is key, especially a urine microanalysis, looking for white blood cell or epithelial casts. Consider a CBC to look for, again, to look for eosinophilia, and a very careful consideration of recent medications. Typical offenders can be antibiotics, antivirals, anti-epileptic drugs, and PPIs, proton inhibitors, proton pump inhibitors. If there is no clear answer from looking through the history, looking through the drugs, doing basic evaluation, then this patient may need a renal biopsy to definitively diagnose drug-induced acute interstitial nephritis to show that interstitial inflammation and tubulitis. How do you treat drug-induced acute interstitial nephritis? Eliminating whatever drug you think is probably the cause, keeping supportive AKI therapy going, and there is conflicting evidence regarding the efficacy of steroids in these patients. A very common offender of drug-induced AIN is vancomycin. The exact mechanism of renal toxicity of vancomycin is not totally defined. Historically, vancomycin-associated acute renal injury has been attributed to acute interstitial nephritis with a delay of injury, but some animal studies suggest there's also a direct oxidative effect to the proximal tubule cells, and this is an increasing problem with the increasing prevalence of MRSA isolates, both in the community and in hospitals. Hemolytic uremic syndrome, or HUS, is a very important cause of intrinsic renal injury. This is defined by the clinical triad of thrombotic microangiopathy with hemolysis, or in other words, microclots in microvessels with hemolysis. There's thrombocytopenia, and there's acute renal insufficiency or acute renal failure. What's the association with HUS? Classically, this is with a GI infection with a shiga-like toxin producing E. coli that is characterized by bloody diarrhea and acute kidney injury in the United States. So for the boards in the United States or Europe, the typical cause is the O157 colon H7 E. coli strain is the most prevalent pathogen, and typically from eating hamburger. In low and middle income countries, it's not so much E. coli, it's more dysentery-associated shigella infections that's a major contributor to hemolytic uremic syndrome. And the pathogenesis in both cases is that you have the shiga-like toxin that colonizes the large intestine, tightly adheres to intestinal epithelial cells. That toxin translocates into the circulation, gets incorporated into neutrophils, which then transfer those cells in the kidney to the glomerular endothelial and tubular epithelial cells, blocking protein synthesis within those cells, stimulating cytokine release and inducing tubular apoptosis and tubular necrosis. So HUS really lies on a spectrum of thrombotic microangiopathies generally. And one framework to think about thrombotic microangiopathies is with the picture here, where you can have primary thrombotic microangiopathy from either a genetic source, if you have a mutation in your ADAMS-TS13 protein, or if you have a complement mutation that predisposes you to a typical HUS, or you can also have primary thrombotic microangiopathy that's acquired with an autoantibody of some form. You can have infection-associated thrombotic microangiopathy, which is where classic HUS would fall, either from E. coli or from pneumococcus, also from HIV and from COVID has been described. And then lastly, secondary thrombotic microangiopathy from a variety of causes, including post-hematopoietic stem cell treatment, post-organ transplant, post-associated with pregnancy, associated with autoimmune disease, associated with cancer globally, and also associated with drugs. And in all of those, your key is recognition with an acute drop in hemoglobin and platelets, increase in LDH and decrease in haploglobin from the hemolysis with AKI. And then depending on the primary cause, you may or may not have an element of DIC as well. Lastly, to talk about post-renal etiologies of acute kidney injury, typically this is not too difficult to identify from a good history, and you can generally identify them with imaging. The major concern for post-renal causes of acute kidney injury is you can have a post-obstructive relief diuresis, which can be quite dramatic and can generate significant electrolyte abnormalities as part of it. So what are the management priorities in AKI? So this is an important figure taken from the CADIGO guidelines that kind of stratifies strategies for management by stage of AKI. So for all stages of AKI, you want to try to discontinue all nephrotoxic agents wherever you can. You want to ensure adequate volume status and kidney perfusion pressure, thinking back to that diagram of why blood pressure is so important for the glomerulus. You want to consider functional hemodynamic monitoring, i.e. an arterial line, potentially a CVP, monitoring serum creatinine and urine output carefully, avoiding hyperglycemia, and then considering any alternatives to anything that would require radio contrast, which would worsen any type of AKI in the acute period. For more severe forms of AKI, stage 1 and above, trying to use any type of non-invasive method that you can for diagnostic workup, but if that's not illustrative, then considering invasive modalities like a kidney biopsy. For stage 2 and above, making sure that you're changing drug dosing appropriately for the estimated GFR that you have, thinking early about renal replacement therapy, and considering an ICU admission for more closer monitoring. And then lastly for stage 3 and above, avoiding the presence of a subclavian CVC if possible, so that you avoid the possibility of a thrombosed vessel, which would complicate long-term dialysis options. What about fluid management goals with acute kidney injury? Here the important thing is to think about that standard maintenance IV fluid calculations, in other words, the 4-2-1 rule that we all learn is based on assumption of a normal renal function. And so in cases of severe AKI, it is much more reasonable to think about only replacing insensible losses, plus replacement of any ongoing losses. And the typical estimate for insensible losses is 400 mLs per meter squared, or ballpark one-quarter maintenance IV fluid calculation, plus whatever you have for ongoing losses, and making sure that you're having careful monitoring of ins and outs and total fluid status of the patient. Using IV Lasix or IV furosemide can be helpful to try and maintain urine output when you have situations of oliguria and arneria. And early awareness of fluid overload is very key in situations with acute kidney injury. Percent fluid overload has, there's two different methodologies that are used to calculate percent fluid overload, either the current weight minus the ICU admission weight, or the total sum of the daily fluid in minus fluid out divided by the admission weight, with the former being the more common formula that's typically used. And we know fluid, calculating this is important because we know that higher fluid overload states are associated with increased mortality risk independent of what the cause of the fluid overload is, somewhere around three times increased mortality. The typical threshold for intervention is somewhere around 10% fluid overload, although within the podium definitions they use a more conservative threshold of 20% as the threshold for intervention and dysfunction. Why is fluid overload important? It causes multiple types of adverse sequelae. It can cause impaired contractility and diastolic dysfunction for the heart. It can cause cerebral edema and increased delirium. It can definitely cause impaired gas exchange due to pulmonary edema in the lungs. It can cause poor nutrient absorption in the GI system and definitely causes impaired wound healing and microcirculatory impairments in tissues due to anisarcha. What about things specifically in the ICU for management of AKI? Here the key is optimizing cardiac output and renal blood flow, as we've already discussed. And so that may involve early initiation of inotropes and vasopressors to support and optimize blood pressures. Trying to do whatever you can to restore and increase urine flows, so that may involve a furosemide or Lasix challenge. Aggressively treating any acute complications from the AKI, which could include things like hyperkalemia, hyponatremia, any acidosis or pulmonary edema, and thinking early about initiation of renal replacement therapy. So what does renal replacement therapy involve? That can be peritoneal dialysis, PD. It can be intermittent hemodialysis, IHD. Or it can involve continuous renal replacement therapy, CRRT, which there are multiple variations of that. And for all of these modalities, the key to how they work is understanding the role of two physical properties, convection and diffusion. So convection involves the hydrostatic pressure of solvent as it pushes solute across a semipermeable membrane, otherwise known as solvent drag or transport. So on one side, you have a high solvent pressure and a high amount of solute. And then that pressure drags solute across the permeable membrane to create convection. Diffusion, however, relates to solute diffusing passively across the semipermeable membrane down the osmolality gradient due to just the random motion of molecules in a solution. And there may or there may not be any difference in solvent pressures, but there doesn't have to be a difference in solvent pressures. So on one side, you have a high osmolality and high amounts of solute, small molecule solutes that are listed there. And then that will move across that semipermeable membrane to the side with low osmolality, which in this case, this would be blood moving into the dialysate, solutes moving from blood into the dialysate. So here's a cartoon to depict how peritoneal dialysis works. So you have a peritoneal dialysis bag, you have it connected to an installation line, which is connected to a peritoneal dialysis catheter, which sits inside the abdominal cavity. And there are typical hourly cycles where you instill the PD fluid, it dwells within the abdominal cavity. So for some period of time, for some period of time, and then you open a stopcock and you drain out that fluid from the abdominal cavity, and then you repeat. So typically, this happens sort of every hour, and it can be automated so that it happens automatically overnight while the patient sleeps. The advantages of peritoneal dialysis is, which only depends on diffusion, there's no convection, is, the advantages are your semi-permeable membrane that allows for diffusion is your peritoneum. It's relatively simple to set up and perform. It's very easy to use in infants because typically it's pretty stable in terms of hemodynamic effects and does not require any anticoagulation. It's placing peritoneal access is a bedside procedure that's not very hard to do. And you can use it to treat severe hypothermia or hyperthermia as well. The disadvantages are is that because you're using the peritoneum as the semi-permeable membrane, you can have unreliable ultrafiltration that happens. It's slow, you have to do it every hour repeatedly. And so that takes time for it to work. So there's slow fluid and solute removal. If there's lots of problems with the belly getting quite big during the dwell cycles, then you can have some respiratory compromise, especially in small infants. You can have issues with hyperglycemia. And then of course you can have all sorts of technical issues with either drainage failure or leakage or obstruction of the catheter. And then always the concern with infection, you can develop peritonitis because you have an indwelling piece of plastic in the abdominal cavity. Intermittent hemodialysis, IHD, also depends on diffusion but is more active than peritoneal dialysis is. In this scenario, you have venous blood that's being drawn off the patient from a dialysis catheter via a pump. It runs through an IHD filter. There's a fresh dialysate that's running countercurrent to the blood. And then on the other end comes out the cleaned blood as it passes through the filter and has been dialysed by the dialysate. And so the exact amount that you clear of whatever solute you're talking about depends on the molecular weight of that molecule, the specific characteristics of the IHD filter that you're running it through, are there big pores, are there small pores, the speed of the dialysate flow. So if the dialysate is running faster, you're going to dialyze more. Similarly, the speed of the blood flow, the faster you run the blood, the more you're going to dialyze with that as well. But the downsides of intermittent hemodialysis is that it happens fast. It's the best therapy for things like severe hyperkalemia and ingestions and gives you the maximum amount of solute clearance for all three modalities. But it can cause quite a bit of hemodynamic instability and you can have rapid fluid and electrolyte shifts and can be difficult to accomplish in small infants because of that hemodynamic instability. As a result, in the PICU, typically for sick patients in the ICU, we use continuous renal replacement therapy. And this is a much more gentle form of continuous fluid and solute removal. And so it's more ideal for the unstable, critically ill patient who doesn't withstand sudden fluid shifts very well. And it's also very effective in fluid removal, electrolyte balance, and removes some small water-soluble toxins like urea. And we typically don't have to systemically anticoagulate the patient. We use what's called regional anticoagulation with citrate and calcium. So here's a cartoon that shows a typical CRRT filter and system. You have blood that's being pumped out of the patient through the hemodialysis filter. As the blood comes out of the patient, citrate is added to anticoagulate the blood. And there can also be the addition of a replacement fluid, what's called pre-dilution. Then due to convection and due to diffusion from the dialysis fluid, you have hemodial filtration that happens. And then all those electrolytes and fluid come off as an ultrafiltrate. And then often there is a replacement fluid that is added post-dilution to correct electrolyte abnormalities and replace anything that needs to be replaced, as well as adding calcium back in just before the cleaned blood goes back to the patient to restore normal coagulation status. In the context of acute liver failure, there are several support options that can be used. CRRT can be used as it's effective in removing small water-soluble toxins such as ammonia and urea, but it can't eliminate large or protein-bound molecules. So things like bilirubin, endotoxin, and cytokines, CRRT is not so effective for. TPE, therapeutic plasmid exchange, does remove protein-bound and large molecules, things like cytokines, but it's very non-selective. And so along with the bad things that you're trying to remove with TPE, you also end up removing a lot of good things, quote-unquote, things like clotting factors that also get removed. And so that has to be monitored for. MARS ELS is the most advanced system for acute liver failure support options. And with this kind of system, you're circulating blood through multiple absorbent systems and combining an albumin-based dialysis with conventional dialysis to try to remove both protein-bound and water-soluble toxins. So I'll show you a cartoon of what MARS ELS looks like. So MARS ELS stands for molecular adsorbents recirculating system extracorporeal liver support. So you have the patient connected with a dialysis catheter with their blood running initially into an albumin-based hemodialysis filter where there's an albumin interface. And that albumin, because it's negatively charged, binds amino acids and other toxic substances like ammonia. Then the fluid that comes out of that MARS filter is run through a typical hemodialysis filter with a countercurrent hemodialysis dialysate, just like before. And then after it runs through the hemodialysis filter, it's run through a charcoal filter, activated charcoal filter to perform anion detoxification, and then through an anion exchange column to restore electroneutrality and electrochemical balance. And then that fluid is circulated back into the MARS filter, which is running continuously as well. So here's a board-style question. So a four-month-old infant is recovering from septic shock and acute respiratory distress syndrome, ARDS. She's hemodynamically stable, and her inotropic compressor support have been discontinued. She remains mechanically ventilated and is tolerating full enteral nutrition. On physical examination, she has obvious anasarca due to her capillary leak syndrome. Currently, she is receiving an infusion of bumetanide at 0.3 milligrams per kilo per hour. Her BUN is 10, her creatinine is 0.3, and her albumin is 3. Her urine output is around 3 mils per kilo per hour, and her CVP is 10 milligrams of mercury. However, her fluid balance remains positive. Of the following, the action that would most likely achieve additional diuretic effect in this patient is, number one, begin treatment with metolazone 0.2 milligrams per kilo per day enterally. Number two, begin treatment with spironolactone 2 milligrams per kilo per day enterally. Number three, change the Bumex infusion dose to 0.4 milligrams per kilo per 24 hours. Number four, change Bumex administration to intermittent dosing of 0.1 milligrams per kilo IV every eight hours. And number five, discontinue Bumex infusion and initiate furosamine infusion at 0.1 milligrams per kilo per hour. And so the answer for this problem is, number one, begin treatment with metolazone. If we look at the other options first, number two, begin treatment with spironolactone. Spironolactone is a very weak diuretic that is typically only used as for its potassium sparing effects in the context of treatment with other diuretics. And so adding spironolactone would not achieve additional diuretic effect and is not the right choice. Number three, change the Bumex infusion dose to 0.4 milligrams per kilo per 24 hours, not per hour, would be a net decrease in the overall Bumex infusion dose. And so that is not the right option. Number four, change Bumex administration to intermittent dosing of 0.1 milligrams per kilo IV every eight hours. Again, this would represent a decrease in the total dosing of Bumex for the patient, and so that's not the right option. Number five, discontinue Bumex infusion and initiate Lasix infusion at 0.1 milligrams per kilo per hour. Lasix is less efficacious compared to Bumex, and so especially at this low dosing, this would again represent a decrease in the total diuretic administration given to this patient, so it's not the right option. Number one, begin treatment with metolazone. Metolazone is a different class of diuretic. It's a thiazide-style diuretic, and so that would work synergistically with Bumex, which is a loop diuretic, and so that would likely achieve additional diuretic effect for this patient, and so that's the correct answer. Thank you very much.

acute kidney injury

AKI

pediatric patients

etiologies

treatment options

renal replacement therapy

fluid management goals

diuretics