It strikes me that the slides have a mind of their own or probably wants to give this talk. So either is fine with me. Let's go back. Can you start us back at the beginning, please? Thank you so much. And yes, Sandy and I did not call each other this morning, but I now wish that we would have. We could have brought you into the blue suit fold. So thanks everybody for joining today. We're gonna be talking about the next frontier in drug stewardship, which is nephrotoxin therapy. These are my disclosures, none of which are relevant. And we're gonna start with the concept of stewardship. So what is stewardship? I dug into this as I was preparing this talk and I was reminded about a lot of things that stewardship is. It may relate to environmental stewardship. It may relate to donor stewardship for development, but ultimately what it gets at is the idea of taking care of other people's stuff. Yet so often it looks a lot more like this, right? I'm a pharmacist and people joke that I am a medication police officer. We're gonna battle with these slides. Do you have a way to stop the advancement? Sounds good, thank you. Or I can just talk. Okay, thank you. Yeah, so it looks a lot more like this, right? Instead of being somebody who takes care of other people's stuff, the patients, the drugs, it becomes so much more about stopping or withholding or preventing or constraining somebody's ability to use the medication that they think is best for the patient, right? So I'm hoping over the next 15 minutes or so that we can have a thoughtful conversation about how to reframe the culture and be more mindful about how we would be caretakers rather than medication police. All right, so for our session objectives, we're gonna talk about the elements of a nephrotoxin stewardship program. And then I'm gonna give you four specific examples of where this is done in current practice. Maybe can we just take it off of slide view and we can just do a casual look at the deck? Cool, yeah. The slide, in case you didn't hear them, the slides have timings on it. In general, nephrotoxicity affects about a quarter of hospitalized patients. And if you look at the cases of drug-associated acute kidney injury, it amounts to about 30% of all of the episodes of acute kidney injury in the hospital. And it doesn't stop when the doors close when you leave the hospital, right? In post-acute care, there is about a 1.4-fold higher risk of acute kidney injury for each exposure to avoidable nephrotoxins. And that increases chronic kidney disease, rehospitalizations, and decreased quality of life for patients. And that's why, in the KDEGO AKI Prevention Bundle, it is the first and foremost thing that we are supposed to be considering, which is preventing nephrotoxins from being used in patients who are at highest risk. Now, when we talk about stewardship, stewardship is not new. This is taken blissfully from the CDC's website, looking at antimicrobial stewardship, which is, of course, where most of this has come from. And we can learn a lot from them. This is a very cute infographic, right? It's super cute. It's put out on the CDC's webpage for everybody to see. And you can see things. Let me see if I can get a laser pointer here. You can see things, like they say 79% of people with CAP should not have gotten antibiotics. 27% of people who are prescribed Vanc shouldn't have gotten it. And what should you do? You should optimize. You should reassess and use diagnostic testing. And you should use the shortest effective duration of therapy. So really, what is antimicrobial stewardship? It's a coordinated set of interventions to assess and measure our approach to appropriate antibiotic selection as it pertains to drug choice, drug dose, duration, and general spectrum of activity. So when you think about this, a lot can be taken forward when we use this goal to understand nephrotoxin stewardship, right? There are some clear core elements that we can bring forward. And I would put them into these four buckets. Core element one is commitment. What the antimicrobial people have on us is power, right? They have the fear and power and train of antimicrobial resistance to jump on. And the CDC and the WHO and the NIH and everybody is throwing tons of resources and commitment at this. And so it's not only commitment from these external forces, but it's institutional commitment. Joint commission, everybody here, raise your hand if you have an antimicrobial stewardship program. Okay, anybody who didn't raise their hand is gonna have a joint commission visit or is asleep. So it is clear that there's institutional commitment and there's external commitment, right? They also have data. So I showed you a little bit of epidemiologic data while the slides were dancing. And we have some within nephrotoxin stewardship, but we don't have that much. We need to do more epidemiologically to demonstrate using the very thoughtful nomenclature that Dr. Kane-Gill just mentioned, how big of a problem this is and where we can make an impact. But the also important thing is to have local data, right? The average person thinks they are above average. And in general at our hospitals, there's a lot more that we can do to measure and assess our own performance, establish metrics that we want to use to improve and then hold ourselves to that. Part of commitment is resourcing the effort. So there's a lot of money that needs to be happening here to try and support any stewardship program. We need personnel, we need technology, we need tools. So that's certainly a part of resourcing. And then this idea of a supportive infrastructure includes toolkits. Nobody expected somebody to just walk in and generate an antimicrobial stewardship program out of thin air, right? You can go to any package of organization websites and find recommendations for prospective audit and feedback, pre-authorization, multidisciplinary team structures. Here's this toolkit, here's this guidance document. Pick your poison. There's so many different ways that people have tried to support institutions in bringing these to bear that we can then use as frameworks for nephrotoxin stewardship programs. So when we look at what nephrotoxin stewardship is, these are some recommendations that Dr. Cain-Gill summarized nicely in a review paper on the topic. Really it has three goals. First, coordinated strategies to enhance medication safety. So what does that mean? Perhaps we should come up with a standardized list of drugs that we're going to pay attention to. I think everybody knows what an antimicrobial is, but do we really know which ones are the nephrotoxins? So as a community, we need to do a better job of coming up with a standardized list, but locally we need to have ones that we think are a priority as well. We also need to come up with coordinated strategies to enhance kidney health. So it's not just about making a consistent list, it's how you use that list to create actions. So perhaps you use that list to be hypervigilant about nephrotoxin burden, like Dr. Cain-Gill mentioned. And then last, akin to the choosing wisely effort, we need to avoid unnecessary costs, monetary or otherwise. So that means using diagnostic tests, perhaps novel biomarkers of kidney health, but only in the places where they're going to add value. So I'm gonna talk about four specific examples of where nephrotoxin stewardship is going on right now. And these I think fairly could be described as grassroots efforts without cute info graphics on the CDC's webpage and all this stuff, but these are having a real patient care impact right now in our field. So the first is the NINJA program. This came out of Cincinnati Children's from Dr. Stu Goldstein. This is a single center project focused on non-critically ill pediatric ward patients. So probably that affects 0% of the people in this room, but just imagine it in the context of your practice. So non-critically ill pediatric floor patients, they developed a list of medications and then they fired an alert to a pharmacist and said this patient is on multiple nephrotoxins, specifically in most cases it was three. And that pharmacist's job was to go to the care team and say they are on three nephrotoxins. We think you should check a serum creatinine. Now you probably all say, oh, adult critically ill patients have serum creatinines all the time, that's true. But in a ward pediatric patient where we're not sticking them every minute of every day, that's not true. So go to the team, tell them to get a creatinine. And then they looked at the metric of did they do that? So what did they find? Well, interestingly, if you look at their nephrotoxic medication exposure here, Y-axis is drug exposure rate, X-axis is time, and the red line is mean exposure rate, they saw a significant downward inflection in exposure to nephrotoxic medications. And reminding you here, this isn't because they said you need to stop that drug that they're on on my list. They said they have a high nephrotoxin burden, check a creatinine. So through that conversation, through that discussion, through that notification, it prompted actions spontaneously by the care team. In addition to decreasing nephrotoxin exposure, they also decreased the acute kidney injury incidence by 25% that was sustained for multiple years and the severity. I'll talk about another one. The slides are probably gonna freak out on this one too, because it'll advance. But this next topic is the Pravacchi trial. So the Pravacchi trial was a clinical trial. For those of you who aren't familiar, it was a study of cardiothoracic surgery patients who they used a novel kidney biomarker, in this case, TAMP2-IGFBP7, which is marketed as Never Check in the Urine. So they ran them through cardiac surgery, they checked the postoperative urine biomarker, and the patients who had a biomarker elevation were considered high risk for post-op acute kidney injury. And then they randomized that enriched population, so it's a form of prognostic enrichment for clinical trials. And they randomized that population to either the prevention bundle, which was shown on an earlier slide, or control, do whatever you want. And then they looked at the incidence and severity of acute kidney injury and demonstrated a reduction in stage two to three acute kidney injury. So it was a general success. Small study, single center, but definitely promising. What's interesting about Pravacchi is they went on, the same group went on to do a multicenter study. The multicenter study was conducted in Germany, Belgium, Spain, Italy, and the UK. And the goal of the multicenter study was different. It was not to test the Pravacchi bundle and the impact on AKI, it was to test whether it could be done. So the goal was adherence to the bundle. So if we look at the data from adherence to the bundle, what you can see here on the left is the primary outcome of all or non-bundle compliance. And this is all of the pieces generally of the KDGO bundle. And you can see that in the intervention group reflected in the red, that statistically significantly better adherence to the Pravacchi bundle or the AKI prevention bundle than the usual care group. Now you might be critical and you might say, only 65% of people got the intervention. That is fine to say, but in a real world application of an intervention, and this is much more likely effectiveness than efficacy, and is pretty good for the world of bundles. I mean, anybody who lived through sepsis bundle implementation can say that this is not bad. Moreover, as I alluded to, a lot of people think they're doing awesome at doing the prevention bundle. It seems intuitive, right? Oh, we don't use Ras inhibition in our post-operative patients. We don't use nephrotoxins. We check serum creatinines. You're wrong, right? If you look here at the usual care patients, only 4% got all of the bundle elements. Now some were worse off than others, right? This hyperglycemia difference may not necessarily be the same in the US versus Europe, but still, if you look at the DC nephrotoxins, which is the focus of today's presentation, 100% bundle compliance in the intervention group, but 15% of patients in usual care had their nephrotoxins perpetuated. That's 15% of people that we could have acted on. So that's low-hanging fruit, guys. This isn't a magic bullet for AKI. This is stuff that can be done today. Moreover, what can be shown with the Pravaki trials, as well as the Big Pack trial, which was a very similar design in abdominal surgery, is that they have an impact. So this is a number needed to treat of around six to 10. So you go to your centers, you make sure that your patients who are high-risk get their glucose controlled, their nephrotoxins optimized, their serum creatinine monitored, their hemodynamics and fluid teed up, and for every 10 of those you do, you save one patient an episode of stage two or three acute kidney injury, which, summarizing more plainly, could mean dialysis for a patient, acutely, or lifelong. You might spare a patient lifelong dialysis. So that's really a big impact, potentially, for that type of intervention. All right, the third one I should just let Sandy present, because it is her work. This comes from UBMC. They reported out on data from two academic hospitals, where in this case they looked at the use of an alert for high nephrotoxin burden patients in the critical care setting. So patients who had a high nephrotoxin burden were screened, and then, if appropriate, the pharmacist engaged and ordered a novel urinary biomarker, which, if elevated, then was used to motivate clinical action, including deployment of a prevention bundle. And if you look at the preliminary results here as a representative example, among the high-risk patients that were identified, you can see that actions were taken. A quarter of the patients had their drug doses adjusted, a third had nephrotoxic medications discontinued, and many more had therapeutic drug monitoring. So there are things that we can be doing to take actions to help our patients. And then the last thing I want to mention is some work from our center, which talks about the importance of not discontinuing care at the close of the hospitalization. There is this tremendous cavern that exists when you leave the hospital, because we have inpatient people and we have outpatient people, right? And the care continuum is broken. But yet acute kidney injury survivors bring with them a collection of issues when they leave, including kidney health-related things and many more. So we developed an AKI care delivery model that is intended to be holistic and embedded within primary care and made sure that these patients engaged with a pharmacist. And those pharmacists that saw the AKI survivors identified a number of different medication therapy interventions that could be improved, on average three or so per patient, of which about 20% of them related to renally eliminated or nephrotoxic medication. So this may be helping patients discontinue NSAID therapies, or it may be finding a great candidate for an SGLT2. So there's lots of ways that a person who is transitioning out of the acute care setting into the post-acute care setting can be supported in their process of survivorship. So I imagine we have a few people here who work in the PICS space. Do we have anybody in the PICS environment? Yeah, so this isn't a good example of a type of intervention that you could look at in a PICS patient, right? What about their kidney survivorship can we act on? I'll conclude by saying, as I did earlier, there are so many pieces about stewardship that we can learn from existing programs. Whether it be antimicrobial stewardship or opioid stewardship or whatever, we need to, as a community, recognize that nephrotoxin stewardship is important. It's not a foregone conclusion that patients who have evidence of AKI or drug-induced kidney disease need to stay on their bank. We need to prioritize, for example, having difficult conversations about whether that last nephron should be spared or we should withhold the lenazulate, right? These things do not exist in silos. They need to be comprehensive, patient-centered conversations. We need epidemiologic data that is based in thoughtful nomenclature. And we need to look at our local performance critically and measure our response to beneficial activities. We need the institution to invest resources, organizations to invest resources, to develop tools that we can use to help people facilitate bringing these programs into their practice. And ultimately, as critical care practitioners, right now, nephrotoxin stewardship is going to be grassroots. And so this is something that each of us bears responsibility in trying to carry forward. Thank you, and I think Sandy and I will take any questions.

nephrotoxin therapy

drug stewardship

concept of stewardship

nephrotoxin stewardship program

patient-centered conversations