Hello, my name is Dana Furman and I'm a Pediatric Intensivist Nephrologist in Pittsburgh, Pennsylvania, and I want to give the organizers of SCCM a big thank you for giving me the opportunity to present, and certainly Dr. Basu for involving me in this workshop on saving the kidneys. I promise this will be an exciting set of presentations. I have the opportunity to start things off with some introduction. We're going to talk in the next 15-20 minutes about AKI symptoms. AKI is a syndrome and hopefully display some misconceptions about AKI and get you thinking a little more deeply about the way you approach your patients with AKI. So I have no disclosures. So why are we all here today? Many of you may know, and if you're not, I think this workshop will change your perception of this, that AKI is common. AKI is associated with morbidity and significant mortality, with about 7 million people dying of AKI worldwide per year. And when the kidneys are not working, it makes it challenging to take care of other organ systems. Those of us who work in the ICU and are at bedside frequently, we know that when our patients get AKI, it makes it difficult to take care of not just the kidneys, but organs such as the brain. Encephalopathy, certainly from the buildup of uremic toxins, from fluid overload, absolutely occurs in our patients with AKI. Also, heart function, worsening congestive heart failure, worsening function in our patients with AKI, in large part due to worsening fluid overload. Intestinal function, so edema and buildup of toxins can impede gut function and cause organ morbidity in this space. Exciting that we're seeing more literature in the space of immune function as a result of AKI. We're seeing studies that tell us that patients that get AKI have a harder time fighting infections, an absolute issue with our patients in the ICU. Liver function, in terms of increased fluid overload, can affect this organ as well, and certainly not surprising that lung function is made worse by AKI. Patients that have AKI and have fluid overload can be more difficult to get off the ventilator and certainly suffer from morbidity as a result of that and the effects of more time on the ventilator. So, importantly, how do we define AKI? And this may seem like a simple question, especially now that we do have a lot of data especially now that we do have a agreed upon definition for AKI, but that certainly was not always the case. Prior to now, there are 30 plus definitions in the literature for acute kidney injury, making it very challenging to define at the bedside and, importantly, to define in studies. So, the initial AKI diagnostic construct is the RIFLE criteria. And this provides both urine output and serum creatinine staging criteria for AKI. It was introduced in the literature in 2004 and was followed by the AKIN criteria or the AKI network criteria, which was put forth in 2007. As shown here by this table, in comparing the different AKI definitions, both the RIFLE criteria and the AKIN criteria include an increase in creatinine of 1.5 from baseline over seven days. The AKIN criteria also includes an increase in serum creatinine from baseline greater than or equal to 0.3 over 48 hours. And all the criteria include urine output as part of the definition, importantly, and we'll talk more about that in some future slides. In 2007, the pediatric RIFLE criteria was introduced, including important pediatric nuances to the definition. And then, subsequently, in 2012, the CADIGO criteria, the kidney disease improving global outcomes criteria, was put forth in the literature. And this criteria has been validated and studied in both children and adults, includes elements of all the prior criteria and is the current definition that we use for defining AKI as shown here. So why is it important that I mentioned some of this to have a standardized definition for AKI? Certainly not AKI is considered equal. It's necessary to have a standardized definition so we can follow changes in kidney function. Important to standardize AKI as a heart outcome. If we're going to study it, this is how we have learned or investigators have learned that AKI is associated with morbidity and mortality. And with 30 plus definitions in the literature, as one can imagine, it's very challenging to compare patient populations in studies. And so now having one heart outcome that we agree upon, it allows us to do just that. So again, the 2012 CADIGO, initially proposed CADIGO criteria is what we currently use. There are nuances to this that we're going to touch on throughout the session throughout today. So I mentioned AKI is common. Don't have to take my word for it. Here's proof. It's common in adults. This is a, this is the AKI epi study. This was a multi-center international study of critically ill adult patients. In this cohort, 57.3% of patients developed AKI and 38.9% developed severe or what we consider stage two or three CADIGO AKI. Not just older adults, but young adults as well are not spared from AKI. Here in Pittsburgh, we looked at this specifically in 16 to 25 year olds, a cohort of 8,200 adult critically ill patients. And we found in this younger cohort, 39.8% were developing AKI to 21.3% developed severe AKI. So certainly not sparing the younger patients. AKI is absolutely common in children as well. The AWARE study or the assessment of worldwide AKI, renal angina and epidemiology study. This is a multi-center multinational study that looked at 5,200 children across 10 countries. And the AWARE investigators report that 27% of critically ill children develop AKI and 12% develop severe AKI. So really no patient population is spared in terms of AKI risk, both in and outside the ICU. So classifying AKI, once you have, you suspected or you've defined it in a patient, this anatomic flow model probably looks familiar to a lot of you for classifying AKI. This is taught in a lot of medical school classes and certainly on a lot of nephrology rotations. On the left hand column listed are common indices that we can get at bedside on our patients. And then a lot of times we classify as either, quote unquote, pre-renal AKI or intrinsic AKI. And certainly these are important elements, I would say, as you're tooled out for classifying and identifying and treating patients with AKI. But we're going to push you during this session and this workshop in general to think beyond this classification system. One way to think about this, and again, what I would challenge you to think about for classifying AKI, it's really beneficial to distinguish between conditions that reduce glomerular function and result in the injury of tubules or glomeruli and those that don't. And so thinking well beyond just those indices and not using those as hard methods to determine for treatment. I think as an example is a patient with low cardiac output who has an increase in serum creatinine from 0.4 to 0.8. Certainly this patient, this happens over 24 hours and this patient meets criteria for AKI as we discussed. And the patient, AFINA is acquired or a fractional excretion of sodium and that value is 0.5%. And the patient has a urine specific gravity of 1030. And what you would classify as, quote unquote, pre-renal, do you then get more fluid? And while really conceptually attractive, there's little evidence that a low cardiac output causes AKI due to compromised, anti-grade cardiac blood flow. Instead, there's really more ample evidence that cardiac patients in a medical or surgical setting are at risk of developing AKI due to more venous hypertension. So increased central venous pressure and low output cardiac failure can cause sodium retention by the kidneys with further volume expansion and edema and exacerbate the process. So a patient with cardio-renal syndrome may be harmed by being considered, quote unquote, pre-renal as by using those indices and giving more fluids to that patient could in fact be harmful. So providing this as an example of many patient scenarios where really, again, thinking beyond that construct is important for patients. Another important consideration when defining and approaching patients with AKI, this is a common figure. This data is out of the University of Alabama at Birmingham and telling you that severity matters. So in terms of staging AKI, there is an increase mortality and morbidity with moving from stage one to stage three, as shown here. And in a simple way, we have liquid gold available or AKI urine available from our patients. Certainly not all patients in AKI will provide urine output, but when they do, important to quantify or the absence of urine output, very important to quantify as part of our AKI definition. So this is data from a sub-study from the AWARE trial. Published in PCCM not too long ago, and the AWARE investigators looked at patients with just severe acute kidney injury. So this left-sided figure here, 85% of the group didn't have severe AKI. And again, specifically this 15% that developed severe AKI. And when you look at this group, specifically this 15% that developed severe AKI, it's specifically this 15% is shown here on this right-sided figure. And you look at it broken up by urine output and serum creatinine criteria individually. So 82% of those with severe AKI met creatinine criteria. 31% met urine output criteria. And then importantly, this group, this 18% that was defined by only urine output would have been missed if only the creatinine criteria were applied. So you're absolutely going to miss patients in terms of diagnosing AKI if you're only using creatinine criteria. And again, this is a pediatric study. This has been shown in adults as well for all patient populations in terms of the importance of not forgetting about urine output in that definition. So we have our urine output and our serum creatinine defining criteria, but really defines AKI broadly without precision to the type of injury. And others in this master's course are going to get into this in much more detail. But this current diagnostic paradigm is not precise. It's not applicable to a constantly changing disease process like AKI. And it's not particularly helpful for guiding management in terms of once you've defined the change in serum creatinine or urine output, what do we do with this information? There are certainly limitations to serum creatinine as using it as the only biomarker, because certainly creatinine is the readily available bedside biomarker that we use for defining AKI. This is a great figure from C. Jason by Kathleen Wu and colleagues, really showing us it takes as long as 72 hours post-injury to detect a rise in serum creatinine, really for a number of reasons. And this green line here shows what an individual's actual serum creatinine may be. However, volume expansion, as we see here on the blue dotted line, may lower serum creatinine and delay recognition of a decline in GFR, whereas volume contraction, as shown here in the blue solid line, can induce an increase in serum creatinine despite an absence of actual injury. And then also shown here on this figure is patients with low muscle mass, for example. So the red dotted line here showing a patient with low muscle mass may have a decreased production of creatinine and at risk for unrecognition of AKI. So certainly muscle mass issues that can occur with patients that are critically ill and children certainly can delay our recognition of AKI. So yes, creatinine is readily available and we have criteria for defining AKI using serum creatinine, but being aware of the limitations of serum creatinine when we're caring for our patients is absolutely imperative. So challenging you to think of AKI as a group of syndromes, and others are going to get into this more during this workshop. And those syndromes, you could think about sepsis-associated AKI, nephrotoxic AKI, cardio renal syndrome, as I touched on very briefly, abdominal compartment syndrome, cardiac surgery associated AKI, glomerulonephritis, obstructive AKI, and hepatorenal syndrome, just to name a few. And exciting and very more new information in terms of how we classify and define AKI. The consensus statement of the 23rd ADKI meeting, which was published in 2020, suggested that damage biomarkers should be incorporated into the AKI definition to really augment its classification. Shown here is their proposed new defining criteria for AKI. Importantly, though, and others will talk about this as well, is damaged biomarkers should not be included in the risk assessment of all of our patients. The sensitivity would be low. Really, a patient's AKI risk profile needs to be considered. Importantly, the judicious use of biomarkers should not be included in the risk assessment of all of our patients. And again, exciting others are going to get into this in the following sessions, but important to note when considering the use of biomarkers, not just using them in every single one of our patients that we're considering AKI. So to conclude my portion of this so we can get on to the other speakers, there are some statements that I'd really like you to ponder as we move into an exciting afternoon. AKI is a collection of syndromes with multiple etiologies. The etiology is oftentimes multifactorial, even within a specific subpopulation, and biomarkers can be used to target patient phenotypes and improve monitoring and treatment. And certainly thinking about fluid overload, also thinking about patient muscle mass when you're assessing AKI, recognizing the limitations of serum creatinine, also paying attention to urine output in defining AKI. And treatment and management should be aimed at the underlying etiology, not just those indices that we classically think about, and not just do I give fluid or do I not give fluid, paying attention to the nuances of these diagnoses in our patients. And so with that, I thank you for your time and certainly at the end of the session would welcome any further questions. Thank you.

acute kidney injury

AKI

organ systems

standardized definition

morbidity and mortality