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Gonzalo Matzumura, MD: [00:00:00] We’re starting to understand both on the very acute and also on the recovery side, that actually probably less dialysis is better overall for the patients, but that we do have to intervene in a timely manner. Right? Because delaying it too long, right there, there’s this kind of like, um, sweet spot, kind of Goldilocks kind of period.

Yeah. Sweet spot too early or too late can actually be counter. 

Nicole Kupchik: This is the sepsis spectrum, a podcast about antimicrobial resistance, sepsis, and how to expect the unexpected in your practice.

Josh Woodward: My name is Josh Woodward and this, and Chelsea. This is my wife, Chelsea Woodward. And I’m gonna talk a little bit about our sepsis journey today. I remember right around February, maybe second or third, uh, I clocked out of the firehouse one day. I was feeling a little bit under the weather, um, but I wasn’t really alarmed.

I was, you know, I had a low grade fever of [00:01:00] maybe 99. Um, so not too terrible. A couple of aches. And I had a spot in my right armpit right in here, uh, as the days progressed. Things kind of started to get worse. There’s another spot on my ribs, um, and that spot is the same thing. It’s red and it’s swollen and, and kind of painful.

So, you know, my wife came down, she saw it was around 5:00 AM I was still awake. And she’s like, why don’t we just take you to the er? I remember one of the first signs I noticed, um, that I didn’t realize it at the time, but looking back on it, I always mention it ’cause, um, IUI used the restroom before. I went to the er and I remember that night I didn’t sleep and I drank like over a gallon of water feeling so thirsty, but never having to feel like I had to use the bathroom.

And I, I went to use the bathroom before I went to the hospital and my urine was like dark, like as dark as I’ve ever seen it. Like, like iced tea, like [00:02:00] brown. Um, so I was like, well, that’s kind of alarming. So I got checked into the hospital. Um. Next thing you know, uh, the doctor’s coming in telling me that I’m going into septic shock and they need to operate on me right away.

And that would be about a two to three hour surgery to open up some of the infected tissue and, and see what was going on. Um, I said, okay, but I woke up not two to three hours later. I woke up 10 days later, uh, 10 days later thinking it was the same day. So as it stands now, I’m a double amputee. Um, as far as kidney treatments go, I had some.

Pretty severe, pretty severe kidney issues going into it. I thought I was gonna be on dialysis for a long time. Um, I was on dialysis seven days a week for roughly three or four weeks while I was in the hospital. Luckily, um, when I, when I got outta the hospital, I didn’t need, uh, dialysis anymore, but I have.

Much more conscious of the things I drink, how I [00:03:00] continue to take care of my body. If you’re worried you have sepsis, um, this is your life, this is your body. So take the initiative, go to the hospital, and if you’re worried about them missing it or like missing something or passing off as of flu, just say out loud, like say it to the nurse, like, Hey, I’m, I’m worried this might be SEPs.

You know, um, just getting that out there will really get, get things in motion and get things moving along.

Nicole Kupchik: Hi everyone, and welcome to the sepsis spectrum. I’m Nicole Kupchik, critical care nurse, clinical nurse specialist, and your guide through the unpredictable world of sepsis, or as we like to call this season sepsis and multi-organ dysfunction. Today we’re turning our attention to one of the body’s most silent but vital players, the kidneys.

More specifically, taking a close look at the relationship between sepsis and kidney injury and how infection, inflammation, and fluid shifts can quietly overwhelm one of the body’s most resilient organs. [00:04:00] The clip we just played was from Josh. Josh is a firefighter and sepsis survivor who went from a few red spots on his skin to full blown septic shock.

In just a matter of days, his kidneys failed, his body shut down, and for weeks he relied on dialysis to survive. Josh’s story is a huge reminder that when the kidneys falter, it’s not just a lab value in a chart. It’s a turning point. Fluids build up, toxins rise, and the balance that keeps every organ stable begins to collapse.

I’m fascinated by what’s happening inside the kidneys during sepsis, so it’s a perfect time to be joined today by Dr. Gonzalo Matzumura, assistant Professor of Medicine in the division of Nephrology at Washington University School of Medicine. Dr. Matzumura studies how sepsis disrupts renal perfusion, damages tubular cells, and triggers inflammation that extends beyond the kidneys.

His [00:05:00] work sheds valuable light on why early recognition, fluid management and renal support can make the difference between recovery and long-term disease. The kidneys, how they act as both victims and amplifiers in sepsis. How to interpret the early warning signs of renal failure and what recovery really means.

Once the filters start to fail, stick around. We’ll be right back with Dr. Gonzalo Matzumura.

I am so excited today to be joined by Dr. Matzumura, who is a nephrologist and the associate professor of medicine. So welcome to the show. 

Gonzalo Matzumura, MD: Thank you. Um, thank you for having me. 

Nicole Kupchik: All right. I am so excited to dig in. So you do a lot of clinical work at the bedside and you see septic patients who commonly have acute kidney injury.

I bet you spend a lot of your day writing orders, [00:06:00] I’m just gonna assume for either CRRT, continuous renal replacement therapy, or for hemodialysis who’ve undergone, you know, septic shock or sepsis. 

Gonzalo Matzumura, MD: Yeah, that’s correct. So I think. Probably the, the most common indication for, uh, or the bulk of the patients that we see on the inpatient side in, in the hospital has to do with AKI and particularly severe AKI.

Right. And out of those patients that have developed severe AKI, um, you know, the, a large portion of them are patients that have, that have had sepsis as the underlying cause, right? Um, probably AKI in the ICU, um. Happens about half of the time with within, within the first week of admission in those patients that develop, um, AKI to the point that it needs some form of kidney replacement therapy, mortality can be upwards of 50%.

So, um, AKI is a pretty significant sort of, uh, disease sort of modifying factor that can affect prognosis of a lot of these, a lot of [00:07:00] critically ill patients. Right. Um, and in the particular case of sepsis, sepsis associated AKI is the most common cause of. In the I, right? 45 to 70% of patients that develop AKI in the IC can have an underlying diagnosis of sepsis.

Because of that, um, we, you know, we have to be sort of very, very aware of it and also try to be as proactive possible in managing, because that can help prevent long-term complications. Because I think the problem with AKI is that people sometimes think about it just as a sort of like biochemical and transient abnormality.

Um, but I think we, we are increasingly more and more aware that effects a extend far beyond just sort of.

Um. You know, with AKI, if they recover from, from this kind of acute illness, they, they could progress to something like ckd. Um, they could also sort of have, they, they, they have decrease in, in their quality of life. [00:08:00] And, you know, they have even increased mortality within that first year, after that episode of AKI.

So. Um, there, there are a number of, I, I think the paradigm for, for AKI is changing a little bit in that it’s just not like, oh, this, this transient episode and if things are, are okay after or after this, but it’s, we have to try to prevent it and also be very aware of the patients that have suffered AKI so that we can do anything that we can’t do, sort of improve their long-term health outcomes.

Nicole Kupchik: So I guess when you think about prevention, what do you think is causing a lot of the K AKI? Do you think it’s hypoperfusion, hypotension and shock, or is there something more and is there a stronger tie with sepsis that’s actually leading to kidney injury? 

Gonzalo Matzumura, MD: I, I think that’s a really good question because for the longest time, I think the paradigm or, or, or our understanding of AKI that happened in the setting of sepsis was kind of this generic, um, insult that would be to hypoperfusion low [00:09:00] blood pressure, less blood flow to the kidney, you know, acute tubular necrosis, and that’s how AKI would come along.

But, um, I think as, as we start understanding sepsis a little bit better and also de defining AKI in sepsis better, we’re starting to realize that there’s, it, it’s much more complex and heterogeneous, right? And it’s more, way more multifactorial. So there’s definitely some sepsis specific factors that, that are at play there.

You know, things like sort of inflammatory injury from cytokines and, and sort of immune cell activation. Um. We know there’s some degree of micro circulatory dysfunction as well with, with kind of blood flow being shunted away from the kidneys. Um, there’s a, at a cellular level, there’s mitochondrial dysfunction too, and even some bacterial, uh, products and or, uh, inflammatory products can actually cause direct endothelial injury and tubular injury.

Right. So, um, kind of thinking about these sort of. Factors that are irrespective of blood flow, I think has allowed us to think that there, there could be some [00:10:00] other potential therapeutic targets to, um, managing sepsis associated AKI, right? And then, um, you know, to make things. I guess more complex. There are some factors that are associated with the treatment of sepsis itself, right?

So we know like certain antibiotics can be nephrotoxic. So in a kidney that is already kind of suffering, we add on nephrotoxic medications and things like antibiotics or patients that have been on RAs inhibitors before, or, you know, vasopressors themself will cause worsened renal perfusion. So I think it, it, it’s way more complex than just, oh, you know, it, this is a patient in septic shock or hypotensive.

And because of that they’ve developed AKI. Sort of this whole, the, the, these other factors that we have to be very keen and, and that allows us, I think, to risk stratify these patients even before, um, to kind of be able to identify like, oh, this patient has, you know, risk factors for AKI. Like they have underlying CKD, they’re diabetic, they are hypertensive, they have a smoking history, and so hence they, they’re probably gonna be more [00:11:00] vulnerable and susceptible to, um, developing AKI in the setting of.

Sepsis, 

Nicole Kupchik: which makes everything just so much more complex. Right. You know, when they’ve got these big histories. So, so lemme ask you just a super quick question and a super quick answer. Uh, so for those of you who are listening who work at the bedside, um, so some advice for those people, uh, what are the antibiotics that you look at their list and you’re like, shoot, like that could really harm their kidneys.

Like we always think of like Vanco and Genamicin, but like what other ones? 

Gonzalo Matzumura, MD: Well, I, I, I would probably say most of them when, when dosed correctly. But, but, but that’s the other thing, right? That it, that is, is, is this whole kind of other topic really, that the way we dose antibiotics and AKI is really complex, right?

Because a lot of times we’re going off and, and this is kind of, we’re, we’re going off on a tangent here, but, um, you know, the way we assess clearance and, and, and kidney function during an episode of AKI, when. Kidney function is changing by the [00:12:00] hour or by, by the day, is really imperfect, right? So we could be dosing antibiotics correctly for a specific GFR, but it very well might be that that’s actually not the patient’s true GFR.

And we actually are overdosing and in the process making, you know, causing more damage. I think as, as you kind of pointed out. Yeah. The ones that we are definitely much more aware of and that we know have a direct sort of. Effect on the kidneys tend to be vancomycin and, you know, amino glycosides like Gentamycin, amikacin, um, you know, antifungals like amphotericin we know also have sort of this direct nephrotoxicity.

Um, there are other, you know, antibiotics such as beta lactams that can have an in more, kind of like an indirect effect when they’re inducing something like acute interstitial nephritis, but not so much so you know, directly on, on the kidney. But I think the larger sort of problem is that we really. Have a hard time assessing what the patient’s current kidney function is during an episode of AKI, just because we don’t really have the necessary tools [00:13:00] to, you know, and, and, and all of the dosing guidelines for these antibiotics, um, have been done in steady states, right?

Where, where the creatinine is stable, where it’s not changing hour by the hour like it is in, in the case of AKI. So it’s almost like we’re just kind of our best estimate or guess when we’re dosing these antibiotics in AKI. 

Nicole Kupchik: Well, and I think with that said, I mean, you’re an expert, right? You the kidney is, you are an expert.

And do you ever feel frustrated that you get called so late in the game? 

Gonzalo Matzumura, MD: Yes. And I, and I think that is a big problem, uh, of, of the way or just kind of how we. Are defining AKI in general. Right. Um, we, you know, kdigo, which is kind of the big, uh, organization that, that provides guidance for, for, for, for kidney related diseases, um, defines AKI with basically two parameters and that’s creatinine and urine output.

Right. But we know these two markers tend to be flawed because creatinine, um, is sort of [00:14:00] lags behind a lot of times right there, there have been these experiments when, um, so, so we. Typically expect a change in kidney function when creatinine rises, but a lot of times the kidney function is already changing or the patient is undergoing AKI and the creatinine really hasn’t started to change.

So it like to be kind 24, 48 hours. 

Nicole Kupchik: Is it that much? 

Gonzalo Matzumura, MD: Yeah. 24 to 48 hours. It’s pretty, it’s pretty amazing to, to think that, you know well, so by the time that the creatinine starts rising, um, we already, you know, it’s kind of, the horse has left the barn already. 

Nicole Kupchik: Oh. ’cause I, you know, it’s so funny in my head, I, I knew there were lag times.

Like I knew that was a thing, but I had like eight to 12 hours in my head. So you’re saying it can be up to a day lag time? 

Gonzalo Matzumura, MD: Yeah. I, I, I, up to a day later. And we have to also, the other important thing is that we lose, in order for creatinine to start changing and rising, we have to lose a substantial amount of kidney function.

So if there’s. Small changes in kidney function. You know, the patient could already be having some AKI, but maybe the creatinine’s still not gonna arrive. [00:15:00] 

Nicole Kupchik: Yeah. Alright. What are your thoughts about EGFR? 

Gonzalo Matzumura, MD: Yeah, so EGFR is kind of the way we, we try to assess, um, you know, kidney function, right? So it’s using creatinine as an indirect marker to sort of try to get as close as we can to, to the actual EGFR.

But, um, there are hopefully kind of technology and sort of, um. Different biomark are coming along that should help us or could allow us to have a more precise definition of, of GFR. Um, you know, Cystatin C is an upcoming functional biomarker that tends to have a shorter halflife than, than creatinine. So it’ll change faster than creatinine and it tends to be more precise because it’s not affected as by other things like drugs or patient’s muscle mass as creatinine is.

Um, you know, and they’re also some of these, um. Real time, EGFR sort of markers coming, coming to the market hopefully soon. So, you know, with, with these incoming technology, I think we’ll be [00:16:00] able to better quantify or better assess, um, kidney function so that maybe we can find, you know, places where we, we can intervene sooner.

Because I think that is part of the problem that we’re in. We’re, we’re, we’re reaching these patients way too late. By the time that they, they, we think they, they have already developed AKI, um, you know. Our, our interventions are limited at that point. 

Nicole Kupchik: Well, it’s so funny. I worked with this amazing nephrologist for years and he’d walk on the unit and he had this really gruff voice and he’d be like, Nicole, why didn’t they call me two days ago when I actually could have done something?

You know? Yeah. 

Gonzalo Matzumura, MD: Yeah. 

Nicole Kupchik: I’m like, I know I wasn’t working that day. You know, I would just tease around with him, but, but it’s true. You know, and that was one of his frustrations is like, he just got called so late in the game, basically he would get called at the point the patient needs dialysis and is so, has such a metabolic acidosis that you’re like, you know, 

Gonzalo Matzumura, MD: right.

That’s so severe that there’s nothing else to do. 

Nicole Kupchik: And so, I mean, I think if anyone’s listening, especially any intensivist or hospitalist, it’s just [00:17:00] something to think about. Let’s think about our nephrology partners a little earlier. 

Gonzalo Matzumura, MD: Yeah. Yeah. And I think part of it also, to be honest with you though, Nicole, is that the way we’ve understood sort of AKI and the lack of therapeutics also kind of warranted a little, that approach a little bit, right?

Because there’d be like, well, nephrology’s gonna come along and they’re gonna be like, well, we’ll just monitor until we actually need dialysis. Right? So I think we, we’ve kind of gained a little bit of that reputation, but I. That is starting to change, right? Because the better that we’re under the, the more we understand sort of some of these underlying mechanisms and the fact that it, this is just not a hemodynamic injury.

I think also the, the, the sort of the advent of some of these new therapeutic targets, right? So if we target inflammation, there are some sort of clinical trials that are coming out that some anti-inflammatory medications, you know, certain steroids or, or you know, recombinant alkaline phosphatase, you know, um.

More novel, uh, vasoactive drugs like angiotensin two used in the right [00:18:00] setting early on can sometimes protect the kidney from, um, worsening AKI. Right? But I think we’re just starting to have some of these tools so that even if, if we’re able to identify AKI earlier that we wouldn’t be able to do something about it rather than just like, yes, this patient is developing AKI, but we’ll just probably have to monitor.

Nicole Kupchik: Well, and there was some really exciting, um, smaller papers that were published after the AHO three trial that evaluated angiotensin two or Reza as a vasopressor. And again, finding that right subset of patients who would actually benefit from that as a vasopressor. 

Gonzalo Matzumura, MD: Yeah. Yeah. And, and I think we’re, we are gonna be.

Hopefully you’re right. So it’s all about the right patient in the right time to to, to start these interventions. Right. And I think one big step forward from, from the, I think the renal community over the last, um, you know, couple of years has been sort of being able to standardize some definitions for sepsis associated AKI.

Right? Because up until now we’ve had this like hodgepodge of, of [00:19:00] definitions and patients that get included into, into, into clinical trials or, you know, prospective studies. You know, they, they, they, the only thing that they really share is a diagnosis of AKI. But other than that, it, it’s, you know, they, they’re, there are different definitions of when sepsis, you know, came on, you know, um, what parameters are using to monitor, you know, AKI and so.

This definition of SSIS associated a AKI happening within the first seven days or the seven days after sepsis onset and kind of subdividing that between early sepsis associated AKI and late sepsis associated AKI, I think will serve as a, should serve as a framework so that people can kind of be able to class sub classify these patients on, on this very distinct phenotype, uh, to, to better understand what therapeutics can be applied early in sepsis as AKI I latent sepsis of AKI.

Sort of, uh, be being able to, to, to just understand this, this pathologic process better. 

Nicole Kupchik: Yeah. Okay. Well, [00:20:00] exciting. So I can’t wait to hear like what happens in the next 10 years or so. Alright, next thing I wanna chat about, let’s talk about your output goals. Okay. So I, you know, I’ve, I’m a nurse. I’ve worked at the bedside for a lot of years and you know, it.

Traditionally, we all have these orders that say standing orders that say call for urine output less than 30 mils an hour. And you know, I’ll be honest, as a nurse who worked night shift for 14 years, I will milk that fully to get 30 mils so I don’t have to wake up and spending the middle of the night to say you’re output.

But you know, but, but when you look at like all of the nephrology guidelines and the work that’s being done there, you will not find 30 mills. As a year output goal anywhere, it’s a half a mil per kilo per hour. So tell me like, what are your thoughts on urine output goals? Because I think we’ve gotta think about body surface area and you know, like is I’m five foot two is 30 mils uh, an hour a good goal for me?

Probably. But what about that person who’s six foot two? Right? So what are your thoughts on your output goals? 

Gonzalo Matzumura, MD: Yeah. Yeah. And, and I [00:21:00] think. In, in the same vein as, as sort of, um, the way that we’ve used creatinine urine output as, as a marker of, sort of, as a surrogate of kidney function, I think has the advantage of being a little bit more dynamic in, in real time than, than creatinine.

Right. We talked about how creatinine lag behind urine output tends to be a little bit better there. Where, where, you know, if, obviously if the patient is becoming oliguric, but, but, um, that we, we were worried that, you know, maybe AKI is starting to sit off, sit in, but, um, but the reality of it that up would just.

So many other determinants other than, you know. GFR really like, you know, how much are the kidneys working? Because it depends so much as you said on, on sort of patient specific factors. Like, you know, yeah, this patient is, or, or, but, but most importantly, also like volume status, right? If a patient is, is severely volume depleted and they’re really not making much urine, that’s kind of probably the expected response as opposed to the patient.

Floridly overloaded and they’re really not making urine. They, you know, those kidneys were working, if they were putting out urine, they should be putting out some amount of [00:22:00] decent urine output, right? So, um. We typically, at least in my practice, I don’t necessarily go off of a, a specific sort of urine output goal for, you know, hour per hour, but definitely obviously in, in the setting of declining renal function.

Right. From a synthetic perspective, you know, or, or clearance perspective I should say, where, where the kidneys are. We, we see that the potassium’s starting to build up and on top of that, they’re becoming all geared by the hour. I think that that is our sort of indicator that, that the patient’s AKI is progressing and that we should try to be either proactive about what we’re doing or also just start monitoring more carefully and treating to see if there’s anything that we can do to improve, uh, kind of these sepsis of AKI risk factors.

Right. Modify them if possible. 

Nicole Kupchik: Okay. Cool. All right. Next topic. Wanna chat about fluid choice? Yeah. For resuscitation in sepsis. This is a hot topic right now, right? Yeah. Yeah. So is saline normal or should we be thinking about other fluids? All right. What are your thoughts As a [00:23:00] nephrologist? 

Gonzalo Matzumura, MD: Yeah, as a nephrologist, right.

So I think they look, you know, a lot of our colleagues look to us for, for guidance about this, right? Because we tend to be the ones that come up with these like sort of weird fluid combinations. Sometimes they recommend to, to our ICU colleagues or whatnot. But the reality of it, I think, is that there’s, when.

AKI specifically in sepsis associated AKI? I think there’s, there’s a couple of things that we need to be mindful of, right? So one is, first and foremost the amount of fluid that we’re giving our patient, right? So we, I think, uh, especially this consensus group for, for sepsis associated AKI from a DQI sort of recommends aggressive resuscitation.

Similarly to, to, you know, sepsis guideline goals, right? Even for patients that have AKI. But the, the key here is that we have to be. Mindful and very careful about preventing fluid overload, right? Because in this patient that has AKI that is becoming oli uric, it’s very easy to, you know, just pump them up with fluids.

And then by the time that we realize they’re overloaded [00:24:00] and we’re just precipitating the need for kidney replacement therapy. So, um, there’s been, there’s this kind of like. Phased approach that has been proposed where, you know, we resuscitate them aggressively. We sort of optimize them. We stabilize them, but then we deescalate very quickly, right?

So if they’re either to, to prevent precisely volume overload, because if they’re getting overloaded, we know that fluid. Positive fluid balance across the, in, in a JI across the spectrum is, is a a, a poor, a poor prognostic marker. Right? It increases mortality, it increases ventilation days. It, um, it, it increases ICU length of stay.

So we do wanna be careful about not overdoing this, right? Um, and, and specifically in, in the oli patient because a patient that doesn’t have AKI, maybe we can get away with it because they just continue to make urine, right? But if they’re having AKI, this is gonna happen way. Quickly. And then I think in terms of the fluid choice specifically.

Yeah. You know, right after, you know, some of these studies [00:25:00] came out, you know, salt ed, um, smart, yeah, yeah. Smart trial, all of these started coming out. Um, I think there was this shift towards, towards, you know, maybe we should be staying away from things like that, like normal saline that have, you know, this high amount of chloride in them.

But I think that the reality of it is that, you know, first and foremost, you know, smart and salt ed had. Small amounts of, of, of patients that had specifically sepsis. So we don’t really, really know if, if these necessarily, um, are patients with sepsis associated AKI do better or worse with, with, with balanced solutions versus normal saline.

And I think some of the recent sort of meta analysis and, and evidence that we have haven’t really shown a substantial difference. But I think the bottom line is that we should really. Think about sort of what are, what our patient’s biochemical profile is at the time that we need to initiate fluids, right?

If they are hypochloremic at the time of, of, of needing fluid, probably normal saline is the way to go, right? If they are [00:26:00] developing worsening acidosis already at, at this, when we need to fluid resuscitate them, maybe something like a bicarbonate based solution. Is is preferable. Um, you know, albumin has also been shown to have some mortality benefit, but it it, it should be used in the right setting as well, 

Nicole Kupchik: which is looking like shock would be that setting right now, correct?

Right. 

Gonzalo Matzumura, MD: Correct. Mm-hmm. Mm-hmm. Like, like especially if we think either. As an initial fluid choice is, or as a sort of an aju after, after, um, you know, your initial fluid of resuscitation. But I think kind of like with everything in AKI, it has to be this individualized approach, right? Where we just kind have to look at the patient itself, and then based on what the patient needs are, then we should probably pick one or the other.

Because I think outcomes across kind of those four big fluid categories tend to be about the same. Um, you know, starches and, and dex strands. Those, I think we, we were, we’re staying far away from and, and we probably shouldn’t be used because they increased the risk of AKI as well. So, um, but yeah, but that, [00:27:00] those would be my, kind of like my 2 cents in terms of managing fluid in AKI.

Specifically sepsis associated with a 

Nicole Kupchik: Yeah. Well, I think a lot of protocols have really moved away from saline and, and like you said, just perhaps using it. Um, when I, when I say protocols, I mean like sepsis protocols for resuscitation have moved away from saline unless the patient specifically is hyponatremic or hypochloremic, they’re using more balance like lr Plasma A and Normosol, we’re seeing a little bit more too.

Well, we’re gonna go to break and when we come back we are gonna pick up where we left off. And, um, we’re gonna talk about some other topics. Specifically. I wanna talk about the whole idea of using stroke volume, uh, to guide resuscitation. And then we are gonna dive into CRT and hg, when is the right time to start it?

Should we be thinking about the possibility of dialyzing off these bad media, these bad cytokines and cellular mediators? And what, what does that look like? So, I’m so excited to come back.[00:28:00] 

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And now back to the show.

Welcome back. So we’re gonna pick up where we left off and one of the things I wanted to chat with you about is the whole idea of using like a stroke volume measure with the passive leg raise test, or by manually bolusing a patient very rapidly to decide fluid needs in the setting of hypotension. And a lot of us, um, knew about the fresh trial, where they used, um, one of the, uh, noninvasive stroke volume measures, [00:29:00] and what they found was that they were able to significantly, statistically, significantly reduce.

The need for intubation, mechanical ventilation, like they cut by half, and that when they use a stroke volume measure to guide fluid response. Uh. Fluid resuscitation and they also significantly cut dialysis needs. And you had mentioned earlier that fluid overload is definitely a risk factor for kidney injury, but what are your thoughts?

Like is it time that we just invest in hemodynamic monitoring and appropriately guide fluid resuscitation, or what are your thoughts on that? 

Gonzalo Matzumura, MD: Yeah. Yeah. I, I think it’s definitely, you know, something that is gaining more and more traction, right? We, we’ve realized that with the current metrics that we have, you know, measurement of things like, you know, dyna monitoring with, with things like cvp, for example, have become, you know, they’re not as reliable.

Um, you know, but it, but they are necessary, right? Because per precisely, um, you know, [00:30:00] volume. Sort of vol volume overload. Is this, is, is this really, um, sort of, it’s a complication in and of itself of AKI, but it also, it worsens prognosis for AKI, right? Delays renal recovery. You know, the more renal congestion there is, the more you, the ultra filtration we would need to do if the patient would started out renal replacement therapy.

And that usually leads to the more. Across, you know, um, multi-organ sort of, uh, failures. So I, I think, yeah, finding the right balance between tools that we can use for hemodynamic monitoring and how those would inform choices for, you know, fluid, um. Management. I think it’s, it’s probably going to be the one of, one of those important topics, uh, that, that, that should be able to help us in the future prevent AKI and also manage AKI when, when, even when AKI is setting in to manage it more effectively.

For sure. 

Nicole Kupchik: You know, we’ve, I, I think we’ve all decided like it’s time to stop using CVP to decide if [00:31:00] a hypotensive patient needs volume. But I think where we’re using CVPA lot more is when we’ve got that patient that we’re trying to, uh, really stabilize and maybe deescalate and what we’re, I don’t, I know one of the things we’re seeing is like when we see high CVPs, we know that their risk of kidney injury is extremely high.

Gonzalo Matzumura, MD: Yeah. And, and we probably should stop, be, be, be, should stop pumping them with more fluids. Right. And really being proactive about using things like, you know, diuretics for example. ’cause I know a lot of people are kind of a little bit weary about using diuretics in the setting of AKI, but really diuretics can be one of those tools that can help us in the right setting, again, kind of prevent further volume overload that would precipitate the need for something like kidney replacement therapy.

Nicole Kupchik: Yeah. All right. So what are your thoughts? Intermittent pushes of a diuretic or a drip. 

Gonzalo Matzumura, MD: Yeah. And I, and I think that that’s, that’s a, it’s a big question. What, what I’ll tell you in practice what we do here is you rarely do we put them on a diuretic [00:32:00] drip when, when in the setting of, you know, kind of sepsis and AKI.

I think, um, our, our kind of work, uh, workflow here is usually kind of. We abide pretty much with the Furosemide stress test, right? So we’re getting a patient that’s becoming Oli uig, that’s probably developing some degree of AKI. We tend to bolus them with, you know, a milligram per kilogram of Furosemide and kind of assess their response.

And if you really, if they, they put up, you know, more than 200 mls of urine within the first two hours, then we know that we have a little bit more time or there, their chances of turning around in terms of their AKI are way, way higher than if somebody, if we. Do that on a patient that’s overloaded and they literally make no urine, then kind of know that that’s our, our, our call for, for potentially starting them on some form of kidney replacement therapy.

Nicole Kupchik: Alright, so that was my next question is when do you decide it is time they’ve gotta be on some sort of a renal replacement therapy? 

Gonzalo Matzumura, MD: Yeah, and I think that’s been a, a big question that, that the nephrology world had, has been trying to answer for many, many years. And, you know.[00:33:00] 

You know, as, as little as 10 years ago, we didn’t really know the answer to that. Right? But since then, at least five or six big clinical trials have come out that have tried to sort of answer that question and that, well, if we have a patient that has developed AKI, we know that if they’re, they’re developing severe complications such as severe hyperkalemia, they’re overloaded.

They have pulmonary edema that’s affecting their ventilation. If they have severe metabolic acidosis, their uremic, there really is no question we should put them on some form of renal replacement therapy. But what about those patients that we think are heading that way? You know, they’re a little bit hyperemic.

They’re not making as much urine. Is there any benefit of really starting them? Early, right? Maybe we can prevent some of those complications. Maybe they’re not gonna get as sick and we can get them out sooner and maybe lead to earlier renal recovery. But I think the overwhelming evidence, especially, especially of, of the, in, in the ideal ICU trial that actually included patients with septic or sepsis and septic shock, is that there really is no benefit in terms of mortality of starting them [00:34:00] earlier rather than, than kind of waiting.

Some until there’s, they maybe develop some of these more clear indications for renal replacement therapy. Right. Because, and, and the reason being is that a number of patients that we think have AKI but maybe are not gonna turn around, actually don’t end up meeting any form of renal replacement therapy.

Right. 30 to 40% of the patients that were randomized to these arms of like more the conservative strategy where we’re actually not gonna do renal replacement therapy. Didn’t end up going end. Whereas if they would’ve been randomized to the, to the more aggressive arm, they, they had already been started on renal replacement therapy and that didn’t come at a cost of, you know, more complications from the group.

That was, that was kind of waiting longer to start CRT. Right. So I think we are, we’re starting to understand both on the very acute and also on the recovery side, that actually probably less dialysis is. Better overall for the patients, but that we do have to intervene, um, in a timely manner. Right?

Because delaying it too long, right there, there’s this kind of like, um, [00:35:00] sweet spot. Yeah. Kind of Goldilocks kind of period. Yeah. Sweet spot, right? Where, where if we find we, we start on that period, we improve them, but we put too early, too late, can actually be counterproductive right? And lead to more complications and, and, and higher risk of, of, of mortality as well.

Nicole Kupchik: Oh, interesting. Okay. So like, like what would that look like clinically at the bedside? Let’s say you get consulted, you come to the bedside. Um, are you gonna try a Lasix challenge first? Usually. 

Gonzalo Matzumura, MD: Usually, yeah. I, I think that would be usually because that’s kind of the way that we, we think about them, right?

So again, if. They have a, any of those severe complications and they have an AKI, right? Their potassium is like 6.5. They really are struggling with that. Then I think there’s no, no, no question. We should just put them on. But if their potassium is like, say 5.3, you know, their creatinine has gone up to like about 3.5.

They’re making some urine, but maybe in the last, you know, 24 hours, they’ve made 600 mls of urine. Right. Um, they’re starting to get overloaded. Probably that, that’s a good. [00:36:00] Place to do something like IC might stress test. You know, if we had reliable biomarkers, that would also be one place to, to use them maybe.

Um, and typically if they don’t respond to that IC stresses, then we kind of know like, oh yeah. So we probably should get them started sooner rather than later, because this is probably not gonna turn around anytime soon. And then, yeah, and that’s usually when we put them on either. You know, CRRT, you know, continuous renal replacement therapy or hemodialysis.

Here at, at our institution, we have, you know, wide availability of of, of CRT. So most patients that are hemodynamically unstable, they’re on pressors or they’re requiring some degree of ultra filtration, but we need to control that a little bit better. Um, we tend to start them on CRT, then move them over to, uh, kind of our transition therapy, which is prolonged intermittent renal replacement therapy or sled.

And then ultimately as, as the patient sort of continues to recover or again, get more and more hemodynamically stable, we transition eventually to intermittent hemodialysis three times a week. And [00:37:00] that allows us to monitor them for, uh, renal recovery as well a little bit better because we we’re able to see what the clearance is and what the volume output is on, on days where we’re not doing dialysis.

Nicole Kupchik: That that was, I like how you outlined that. That’s actually really nice, I think for a lot of people at the bedside. Just to understand from a nephrologist standpoint. That’s kind of your approach Now, how long are you running patients on sled? How many hours do you usually run ’em? 

Gonzalo Matzumura, MD: So sled in our, in our pro, in our program, it usually runs anywhere between six to 12 hours.

And we actually do it, do have a nocturnal sled program. So that’s, that’s been, uh, sort of. Beneficial in the sense that, for example, it frees up our patients during the day to work with PT to go for their, you know, radiologic imaging procedures. And then they, when they’re gonna be in bed sleeping, mostly that’s when we’re doing their, their, their sled.

So we, we were able to optimize, uh, uh, kind of resources, uh, around their care as well. 

Nicole Kupchik: I love that. Okay. And then, um, when you’re initially making that decision, [00:38:00] do you, like, let’s say you’ve got somebody who’s got acute kidney injury. Do you almost always default to CRRT over hd? 

Gonzalo Matzumura, MD: I would say so. There really has, there’s no clinical data that tells that there’s a mortality benefit between CRT and hd.

Right. Um, so. Depending on the resources available at each each institution, there’s probably not a wrong answer, but the reason why we tend to go to for, for CRRT is primarily because it tends to be a little bit better tolerated from a hemodynamic standpoint, but also importantly, I think especially on these, talking about these patients that are overloaded, it gives us way more flexibility to do a little bit of ultra filtration every hour as opposed to having to do.

A ton of ultra filtration that might not be as well tolerated from a, from a he hemodynamic standpoint. Right. Hypotensive. They’re giving 

Nicole Kupchik: them volume back. Yeah, exactly. And then we’re like just 

Gonzalo Matzumura, MD: kind of doing this back and forth. Yeah. We’re, we’re, we’re just, um, so, so we found that, you know, [00:39:00] in our program.

Starting most of our patients on CRT tends to be kind of our standard, and then we as, as we kind of mentioned, transition them to sled and then eventually hd. I would say the only scenarios where we do HD upfront are if we need, you know, a lot of, of, of clearance, right? It’s a drug intoxication or there’s severely hyperemic because CRT, the reality of it is that the correction of these electrolyte disorders tend to be Yeah, slow and progressive.

So. 

Nicole Kupchik: Okay, so let’s say you could control a future. 

Gonzalo Matzumura, MD: Mm-hmm. 

Nicole Kupchik: And like, what would you, like, where would you like to see things go? Like, like what excites you, um, in the nephrology world about like what’s coming down the pike? Because I’m sure you’ve got a good, your finger on the pulse of like what’s happening in research and I think like what excites you and what would you like to see happen in the next 10 years?

Gonzalo Matzumura, MD: Yeah. So, so I think what I would like love to see is for us to be able to have therapeutic. You know, targets or, or, or agents to treat AKI [00:40:00] early on, right. Since we’ve started to understand that this is more like a multi-system disease that is happening, you know, sub clinically many times before we even start picking it up with our current sort of tools, I think early recognition.

So, you know, kind of being able to finally mainstream some of these biomarkers to really help us sort of catch it early and then something that we can do about. About it, right? So like some of these, um, either anti-inflammatory medications or, or immunoregulatory medications that could allow us potentially, um, to improve or, or to prevent AKI from setting on.

And if it does that, it’s less severe so they, you know, actually end up needing some form of, of kidney replacement therapy. I think that is ultimately what. I would like to see, and I think what, what might end up happening now that we, we are understanding better kind of what the pathophysiology of AKI is in these different disease processes, right?

Because it’s different you knowis as AKI from, for example, cardiac surgery associated AKI, there’s different, you know. Even though up until recently we thought of them [00:41:00] kind of at the same common pathway and you know, we should just kind of treat everybody the same. Um, so I think we’re, we’re, we’re hopefully with, with better definitions, with better, but with, with sort of being a little bit more precise about how we’re, we’re defining these, these events, we’re able to find these things that are able to differentiate them and allow us to intervene, um, on, on, on the, on the disease process.

Nicole Kupchik: Alright, so listen, I’m gonna wrap it up with this. We’ve already decided that they could call you earlier. We, we’ve decided that already. I think I kind of decided that for you. 

Gonzalo Matzumura, MD: Yeah. Yeah. 

Nicole Kupchik: This is an honor of Dr. Fleet, who I worked with forever. But what, um, if you could give a couple bits, pieces of advice to bedside clinicians.

Um, who have a septic patient who is developing AKI? What would, and you can decide how many, like what are the, the few things that you’re gonna say. Think about this, this, and this. These are my takeaways I want you to think about before you make that decision to call me, [00:42:00] don’t delay calling me. But these are some things I want you to think about.

What are. 

Gonzalo Matzumura, MD: So I think the first thing is that when a patient developed AKI, we have to be aware that the fact that they already developed AKI means that this patient is probably gonna do worse compared to, to a patient that does not develop AKI. Right? And it’s not just something transient. So we have to be really proactive about.

Sort of managing it and, and expecting potentially some more associated complications. Right? So I probably need to pay more attention to the fluid balance. I probably need to be at pay attention to make sure that I can sort of tweak anything that I can in terms of your antibiotic coverage or whatever.

So in order for, for, for this process to not progress as as much. Right. And I think second part of it, as we. I guess sort of, um, understand sepsis, sepsis associated AKI a little bit better. Probably earlier intervention is gonna be, uh, something that’s gonna allow us to change the prognosis because as, as we were chat, just chatting about when we, when that patient is kind of already on the pathway of, you know, [00:43:00] needing kidney replacement therapy, you know, there’s, there’s very few things that we can do to, to improve, improve their, the recovery and their prognosis rather, other than just kind of.

Sort of seeing them recover, but prevention of, or, or, or avoiding going into that state is probably one of the things that could kind of get them outta that, of that, of that pathway. Especially if we’re able to identify risk factors that would put them at risk, you know, would, would increase their likelihood of developing AKI.

Nicole Kupchik: I think this is great advice and I’ll, you know, I’ll be honest. I always like, where’s the nephrologist? You know, let’s get him in here because I just think he brings so much, you truly bring so much to patient care and you know, in long term, like I personally cannot imagine having CKD and being dialysis dependent and having to go to a facility three times a week.

To dialyze. Like I personally cannot fathom that. And you know, anytime we can prevent that, um, I think is an, it’s a huge win. It’s a gigantic win. 

Gonzalo Matzumura, MD: Yeah. 

Nicole Kupchik: I just wanna thank you for being here. I [00:44:00] know clinicians are gonna get so much out of this interview, so I just thank you for your expertise and everything you do clinically.

You definitely are appreciated. 

Gonzalo Matzumura, MD: Thank you so much for having me, and it’s been a pleasure.

Nicole Kupchik: That was a really fun episode and discussion, and I think so many times, you know, we get nephrology involved later in the game and I just felt like Dr. Matzumura gave us a lot of really helpful information and things to think about, and I’m also like really excited about what’s coming in the future. As far as maybe earlier biomarkers that could detect acute kidney injuries so that we can intervene earlier and maybe prevent CK, D.

And so there’s so many things we can do at the bedside, like preventing fluid overload, supporting patients from a hemodynamic standpoint, and truly, you know, just early recognition of acute in kidney injury. So I wanna thank you for joining me on today’s episode of the Sepsis [00:45:00] Spectrum. If you have a story you want me to read on the air, visit www.humancontent.com/sepsis.

And if you’re enjoying the sepsis spectrum, we wanna hear about it. Please leave review wherever you’re enjoying this podcast. It helps a ton. You can also reach me in our awesome team@infoatsepsis.org or visit sepsis podcast.org to share any stories of your own questions. Concerns or episode ideas. To learn more about Sepsis Alliance, visit sepsis.org.

The sepsis spectrum is brought to you by Sepsis Alliance. I’m your host, Nicole Kupchik. Our executive producers are Alice Strickland, Hannah Sass, Claudia Orth, and Alex Colvin. Our producers are Aron Korney, Rob Goldman, Shanti Brook, and me Nicole Kupchik. Our post-production producer is Sundua Hassan Nooli.

Our editor and engineer is Jason Portizo, and our music is by Omer Ben-Zvi to learn about sepsis alliance. Is podcast legal disclaimer and compliance policies. You can [00:46:00] visit sepsis podcast.org/disclaimers. The sepsis spectrum is a human content and sepsis alliance production.

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