[SPEAKER_00]: I always found the pathogenesis fascinating as a medical student and resident.
[SPEAKER_00]: I always read.
[SPEAKER_00]: like reading about it, how the field of one organ and the depth affecting the kidneys.
[SPEAKER_00]: And then I started as a fellow sea impatience and consoles and realized how tough those consoles were and how my attendants were also struggling.
[SPEAKER_00]: And it was just such a high degree of uncertainty, which led me to start reading more and more about it and became one of my clinical area of interest.
[SPEAKER_03]: That's Dr. Juan Carlos Villas
[SPEAKER_00]: Hi, I am Juan Caro Villas.
[SPEAKER_00]: I am a nephrologist at Oxford Health in New Orleans.
[SPEAKER_03]: Welcome to the core.
[SPEAKER_03]: I am thy pearls podcast.
[SPEAKER_03]: Bring you high-yield evidence-based pearls.
[SPEAKER_03]: I'm Dr. Schreit Trevetti, and I'm joined by.
[SPEAKER_04]: Hi, I am Dr. Noah Markowitz, a PGY3 internal medicine resident at Montefirre in the Bronx.
[SPEAKER_03]: Today's episode is all things have had a renal syndrome, or HRSAKI, and yes, we're going to be referring to a paternal syndrome as HRS, though and I debated about this so much, and I was like, no, we have to call it a paternal syndrome, but now I'm a full convert, and a paternal is just a muffled say, so you're going to be hearing us say HRS a lot.
[SPEAKER_04]: So this will be a two-part episode, today we'll be talking about diagnosis of HRS and next week we'll be all about treatment.
[SPEAKER_04]: Let's talk about the five pearls we'll be covering today.
[SPEAKER_03]: Remember at the morning test yourself that deeper you're learning gains?
[SPEAKER_04]: Pearl 1.
[SPEAKER_04]: Pathophysiology of HRS.
[SPEAKER_03]: What are the hormonal changes during cirrhosis that make our patients more susceptible to hepatorenal syndrome?
[SPEAKER_04]: Pearl 2, differential diagnosis.
[SPEAKER_03]: How do you approach the differential in a patient with cirrhosis who has AKI?
[SPEAKER_04]: Pearl 3, all about sodium.
[SPEAKER_03]: How do you serum and urine sodium to help us with a differential of AKI in a patient with cirrhosis?
[SPEAKER_04]: Pearl 4, the official diagnosis.
[SPEAKER_03]: How do you actually diagnose hepatorenal syndrome?
[SPEAKER_04]: Pearl 5, all about Alpeman.
[SPEAKER_03]: Is that 48-hour Alpune Challenge always necessary to diagnose HRS?
[SPEAKER_04]: The first thing for us to really appreciate for HRS is to shift our brains not to think in terms of cirrhosis, but to think in terms of portal hypertension.
[SPEAKER_03]: Yeah, and so if we need to really shift our focus to portal hypertension, then let's quickly remind ourselves how that portal hypertension develops.
[SPEAKER_01]: Cerrosis itself is actually just the scarring of the liver, so the more the scarring and inflammation are fat, and you're those kinds of combination of things depending on which kind of liver disease you have, the more that happens, the more that blood can't get through the liver, the higher the penis pressures are in your abdomen, and you start to build a portal hypertension.
[SPEAKER_01]: Patients usually don't present until somebody notices something we are on imaging or they have a complication of oral hypertension, and then typically the most common complication of oral hypertension is acides, which is where that pressure build-up so much that, you know, you start to leak the fluid into the
[SPEAKER_01]: My name's Nick Mezunder.
[SPEAKER_01]: I'm one of the transplant hepatologists here at University of Michigan.
[SPEAKER_01]: My interests are in coral hypertension and the complications and physiology they're in and using that to better treat our liver patients and better.
[SPEAKER_04]: Once someone develops portal hypertension, it's the body's hormonal response that creates an environment that makes my favorite needley organs, the kidneys, so susceptible.
[SPEAKER_00]: So, you start with a cerotic liver, sort of a stiffness, liver stiffness that leads to increased enter-happatic vascular resistance that this process of a hypertensive kind of liver and stiff liver leads to a maladaptive response outside the liver that is going to be opposite.
[SPEAKER_00]: So, there's a maladaptive evasive dilation peripherally in this bloodness or collision in other vascular beds.
[SPEAKER_00]: mostly driven by the release of naturopoxide, so naturopoxide is kind of absent inside the hepaticion also becomes very prominent outside to try to fight this liver cirrhosis state, and as a result you get this peripheral vasodilation.
[SPEAKER_00]: So that is going to
[SPEAKER_00]: kind of start seeing in a signal to your bare receptors, yeah, control, vascular tone to see, okay, we've got to fix that.
[SPEAKER_00]: So we're going to activate a sympathetic nervous system.
[SPEAKER_00]: And we know that the sympathetic nervous system has its own mediators, but also activates better rate with septos, the renonigetensin system.
[SPEAKER_00]: So you also get the renonigetensin system amplified, and both the sympathetic and renonigetensin system are going to lead to this state of
[SPEAKER_00]: trying to re-absorse sodium and water in visceral-street vascular beds.
[SPEAKER_04]: So to recap, because of the stiffness in the liver, the body initially tries to compensate by vasodilating.
[SPEAKER_04]: This vasodilation leads to a state of low-effective circulatory volume.
[SPEAKER_04]: So even though the body is total body volume up, what the kidneys actually sensing is low-perfusion.
[SPEAKER_04]: So what the kidney will do in response is use the RAS system to vasoconstrict.
[SPEAKER_03]: And of course, your favorite organ, the kidney, is just an innocent bystander to that whole cascade that's leading to baso constriction.
[SPEAKER_01]: Also, in the 70s, did some crazy stuff that transplanted a Hacatoreenol syndrome kidney into another person after the patient was cirrhosedide, and the kidney worked great.
[SPEAKER_01]: So, you know, a lot of these things tell us that the kidney itself is kind of working.
[SPEAKER_01]: It's normal.
[SPEAKER_01]: It's just not getting a blood flow and it's because of this weird physiology in a battery and all syndrome.
[SPEAKER_04]: These studies are fascinating.
[SPEAKER_04]: One study that I really loved looked at the angiography of a patient with a paddle renal syndrome.
[SPEAKER_04]: Nothing was perfused through the renal artery, and then on autopsy, once the vasoconstriction was no longer at play, when they did the same angiography, the flow was perfect.
[SPEAKER_04]: The kidney's completely normal.
[SPEAKER_04]: We'll put a really cool picture of this in our show notes.
[SPEAKER_03]: Yeah, it is really neat to see, but again, this all reiterates me.
[SPEAKER_03]: The kidney, again, is an innocent bystander to all that phase of constriction from the hormonal cascade that's causing all this problem.
[SPEAKER_03]: The kidney itself is fine, and it all starts with an awful portal hyper-tension.
[SPEAKER_04]: Gino Shreya, that reminds me, I see a lot of patients who happen to have cirrhosis in their one-liner and when they get an AKI, I kind of cringe when I read the note and under the problem of AKI, the note says,
[SPEAKER_04]: Yeah, it's all the time, and I'm like, they have compensated cirrhosis, they don't have complications from their cirrhosis, and so without that portal hypertension, this is not HRS.
[SPEAKER_04]: Our final expert, Dr. Marina Sterper, a hepatologist from the University of Pennsylvania, will really drive this point home for us.
[SPEAKER_02]: Hi, I'm Marina Sterper.
[SPEAKER_02]: I am a hepatologist at the University of Pennsylvania.
[SPEAKER_02]: If you have compensated cirrhosis for whatever reason, let's say you had hepatitis C and you were treated, you removed the ideology of liver disease, but you have stable cirrhosis.
[SPEAKER_02]: You can live in that state for 10 years and nothing would happen.
[SPEAKER_02]: You don't have to be predisposed to hip-hat or renal syndrome because you don't have necessarily portal hypertension, you don't have worsening your liver.
[SPEAKER_03]: So Noah, you and Dr. Cerbera are saying that if we have a patient who has stable cirrhosis, who has no evidence of portal hypertension on XAM, no sighties on their poukes, by definition, they cannot have hepatoidal syndrome because it's the portal hypertension that's really kicking off this whole cascade.
[SPEAKER_04]: Exactly.
[SPEAKER_04]: The key way I like to reframe HRS is that it is not AKI on Cerosis, but rather AKI on portal hypertension.
[SPEAKER_03]: I like the ring of that.
[SPEAKER_04]: Yeah, so you cannot have HRS without evidence of worsening portal hypertension.
[SPEAKER_04]: It's the portal hypertension that matters, not the Cerosis.
[SPEAKER_03]: awesome and maybe just a draw that connects a little bit more.
[SPEAKER_03]: I'm thinking about patients that come in in a cute liver failure.
[SPEAKER_03]: So these patients, it's this thing things are happening so fast.
[SPEAKER_03]: They don't have time to develop portal hypertension that's going to kick off that whole caskate to even lead to hepatarial syndrome.
[SPEAKER_04]: Yeah, so the next time you see someone with Tylenol toxicity causing acute liver failure in the ICU, if they have an AKI, that's usually ATN.
[SPEAKER_04]: That is not a petal renal syndrome.
[SPEAKER_03]: Yeah, they didn't have enough time for portal hypertension development kickoff that whole cascade.
[SPEAKER_03]: That would even lead to a better renal syndrome.
[SPEAKER_03]: Maybe the last thing to kind of close up the section on important pathophys grounding, I just had such a big aha when we learned about
[SPEAKER_04]: Here we're talking about prostaglandins, and said work essentially by blocking the production of prostaglandins.
[SPEAKER_03]: Yeah, and then as a reminder, in about a real syndrome we have all this phase of construction happening, and so our patients are really relying on that prostaglandins to fight it as much as possible to keep the vessel open.
[SPEAKER_00]: And this is why patients with cirrhosis are so dependent on those prosthetic land they kind of fight in this situation.
[SPEAKER_00]: And this is why if you give an end say to a patient with cirrhosis is like bad news because they are in such a high prosthetic land in state to defend themselves against a high gothic holamine and to state that the minute you drop a prosthetic inhibitor, you essentially shut down riddle circulation and go into an AKF faster than anybody else.
[SPEAKER_04]: It's the summarized pearl one, so Rosus is just a stiff liver, and when we think about her paddle renal syndrome, the physiology here is that because the liver is so stiff, the body is initially going to try and vasodialate.
[SPEAKER_04]: What the vasodialation does, the kidney's sensing low effective circulating volume.
[SPEAKER_04]: What that's going to do is it's going to cause the kidney to turn on the RAS system and vasoconstrict, and the kidney is extremely susceptible to that vasoconstriction.
[SPEAKER_04]: We have good evidence to show that if we can reverse that vasoconstriction, the kidney
[SPEAKER_03]: That's awesome.
[SPEAKER_03]: I think is that we should really be thinking about how to renal syndrome, not as something that can happen if someone has compensated cirrhosis, but it's really going to be in a patient who's developing an A.K.I.I.
[SPEAKER_03]: on portal hypertension as the lovely future Nefrologist no SS.
[SPEAKER_03]: Alright, so now let's use that pathoph is to get into the differential, right?
[SPEAKER_03]: So you have a patient who comes in with a crannand bump who has cirrhosis.
[SPEAKER_03]: How do we unpack what is driving that AKI?
[SPEAKER_00]: They teach us that it's 85% of the times that diagnosis in the history.
[SPEAKER_00]: And it applies to cirrhosis, too.
[SPEAKER_00]: Patient comes in.
[SPEAKER_00]: They were increasing the diabetics because of a site is.
[SPEAKER_00]: Patient was urinating more or comes a little hypotensive.
[SPEAKER_00]: You know, that's a perennial hint right there.
[SPEAKER_00]: Somebody comes with lactylose, increases, and comes with seven-bound volts with a day.
[SPEAKER_00]: because of a headbody against the falloff of the prevention.
[SPEAKER_00]: You know, things are very clear that you've got to think it perinoffed stays is the first option.
[SPEAKER_03]: Okay, so this sounds pretty similar to a typical AKI workup.
[SPEAKER_03]: If you have a good history for perinoff, it's likely perinoff.
[SPEAKER_04]: And sometimes, the story is pretty good for ATN.
[SPEAKER_04]: For example, a patient who comes in with septic shock and has an AKI, that's likely going to be ATN.
[SPEAKER_03]: Right, those situations make sense.
[SPEAKER_03]: But the thing that trips me up is what are the things that just clue us in that this is a pattern renal syndrome going on?
[SPEAKER_04]: Right.
[SPEAKER_04]: So let's unpack that tray.
[SPEAKER_04]: And let's start with something as simple as the vitals.
[SPEAKER_04]: In theory, a patient with HRS is in a very vasodilatory state, and we would expect the blood pressure to be lower than normal.
[SPEAKER_04]: Not low enough to the point that we're talking about shock, but just on the lower side.
[SPEAKER_00]: Okay.
[SPEAKER_00]: Well, look at the vitals science immediately.
[SPEAKER_00]: Okay.
[SPEAKER_00]: If I have a blood pressure of 172 or 82, I mean, I know that that's not going to be HRS.
[SPEAKER_00]: It's just not possible.
[SPEAKER_00]: It's not doesn't fit.
[SPEAKER_03]: Okay, so with a high blood pressure, or hepatoreal syndromes out.
[SPEAKER_04]: Not so fast, Raya, we don't want to be tricked.
[SPEAKER_04]: We don't want to be tricked into thinking that HRS can only happen with a low blood pressure.
[SPEAKER_04]: It's all about relatively low compared to the patient's normal.
[SPEAKER_00]: If you look at the meta-analysis that we published in 2011, that we compile over 20 clinical trials of HRS, that mean the average mean of your pressure on arrival was 76 millimeters of mercury, 76.
[SPEAKER_00]: So you don't have to necessarily have a map of 62 to think HRS.
[SPEAKER_03]: great.
[SPEAKER_03]: So just to put this into context, say we have a patient with, you know, mazzled with complications in terms of portal hypertension, who's coming in with an AKI and their blood pressure is 120 over 80.
[SPEAKER_03]: But you look at the old clinic blood pressures and their blood pressure are usually actually sits at 160 over 90, right?
[SPEAKER_03]: This should really raise concerns about her patternal syndrome.
[SPEAKER_04]: Yeah, so even though a blood pressure of 120 over 80 is normal in this sense, it's relatively well.
[SPEAKER_04]: After blood pressure, the next thing to do, of course, is look for signs of worsening portal hypertension, because throw back to Pearl 1, HRS is all about portal hypertension.
[SPEAKER_02]: I eyeball the patient and I do think that the rubric of generally compensated decompensated or portal hypertension, no portal hypertension is very useful.
[SPEAKER_02]: So I look at the physical exam.
[SPEAKER_02]: So is this patient muscle wasted?
[SPEAKER_02]: Do they have a pertuberant abdomen?
[SPEAKER_02]: Do they have spider angiomina?
[SPEAKER_02]: Do they have bulging flanks?
[SPEAKER_02]: Does this appear to be a decompensated patient?
[SPEAKER_02]: Then I think more likely this could be hepatorenal physiology at least.
[SPEAKER_00]: For instance, documentation of spontaneous bacterial prey to an ITIS, and the literature is very clear that that's one of the most established precipitating factors for HRS.
[SPEAKER_00]: So I'm going to look for that.
[SPEAKER_00]: And then, is this patient coming from frequent paracentesis that there were monthly now were bi-weekly and now they're weekly.
[SPEAKER_00]: So that's telling me some progression of the portal hypertension.
[SPEAKER_03]: All right, so why they took an exam or chart review, we're going to look for signs of a worsening portal hyper-tension.
[SPEAKER_03]: And then on the flip side, if we don't see signs of portal hypertension, the diagnosis can't be a patternals syndrome.
[SPEAKER_04]: So far, we've just been talking about the big three of HRS, pre-renal, and ATN.
[SPEAKER_04]: But it's always humbling to be reminded that it isn't just those three in the differential for AKI and Cerosis.
[SPEAKER_00]: I think the majority of the literature in HRAs and Ecancerosis has concentrated into the idea that it is a try to renal ATNN HRAs and they have tried to sold us this story of a three-way path that is only three options.
[SPEAKER_00]: anywhere between 5-10 or even 15% of your patients may have something else that is not any of those three.
[SPEAKER_00]: I take that very seriously because I feel like that's our role in the fraud.
[SPEAKER_00]: We don't want to miss a GM that could have a completely different approach.
[SPEAKER_00]: So, most of the times there will be a UA on record before we get consulted.
[SPEAKER_00]: And I'm going to look at the UA, there's any evidence of proteinuria, hematuria, glucosituria.
[SPEAKER_00]: Those three things are going to look.
[SPEAKER_04]: As a rule of thumb, in HRS you would expect to see a bland UA, so no protein area, no red blood cells, no casts.
[SPEAKER_00]: If I see that you're analysis showing those parameters, my next step is going to be go back to the history, that this guy has hepatitis B hepatitis C. Oh, look, there's a million viral loads of vitamin A, hepatitis B, two weeks ago.
[SPEAKER_00]: Boom, my suspicion for a hepatitis B associated GN is going to increase.
[SPEAKER_00]: And then we also know that patients with cirrhosis are predisposed to develop secondary
[SPEAKER_04]: So so far, we have the big three of pre-renal ATN and HRS.
[SPEAKER_04]: We have a new glomerular process, and then next on the differential, if you have a patient with really tense A-CIDs, you should always think about abdominal compartments in drum.
[SPEAKER_04]: And this is something that can usually be fixed with a large volume parasynthesis.
[SPEAKER_03]: Yeah, that reminds me of a good rule of thumb in these patients.
[SPEAKER_03]: It's always good to get a bladder scan, right?
[SPEAKER_03]: We don't want to go down a rabbit hole and miss a simple post-renal A-K-I.
[SPEAKER_04]: There's one more feature that's really helpful in narrowing your differential diagnosis.
[SPEAKER_04]: That's sodium.
[SPEAKER_04]: In fact, it's so helpful.
[SPEAKER_04]: We're going to dedicate our entire next pearl to sodium.
[SPEAKER_03]: Yes, so before we move on to sodium, which I'm guessing is your favorite cat ion, as about a nephrologist, let's pre-cap proletue on the different 12 AKI and cirrhosis.
[SPEAKER_03]: And initially, you can think of it similar to our typical AKI workup, right?
[SPEAKER_03]: If the story is concerning for pre-unil, if someone's having increased bowel and misduty lactylose, it's probably a pre-unil AKI.
[SPEAKER_03]: If someone's coming in septic shock, probably ATN, and of course, don't forget about those post-greenal causes of AKI that can also happen in a patient with cirrhosis.
[SPEAKER_04]: And then what makes the special ACI on Cerosis is we have to think about this other diagnosis, this HRS.
[SPEAKER_04]: And remember, it's really an ACI on portal hypertension.
[SPEAKER_04]: So that's what we're looking for.
[SPEAKER_04]: Signs of worsening portal hypertension.
[SPEAKER_04]: More frequent Paris and TCs worsening ACIDs, SPP, and the opposite's also true.
[SPEAKER_04]: If there's no ACIDs, this is an HRS, period.
[SPEAKER_03]: You do love that point.
[SPEAKER_03]: And then also of a patient as a history of Hep B, Hep C, if they have any blood or protein in their urine, we should also be thinking more about galmarin fritus.
[SPEAKER_04]: So in the reasoning process of what is causing that A.K.I.
[SPEAKER_04]: in the patient with cirrhosis, I want to argue the most important diagnostic factor we need to talk about is sodium.
[SPEAKER_04]: Like most things in life, it always goes back to sodium.
[SPEAKER_03]: very, very cute.
[SPEAKER_03]: I agree.
[SPEAKER_03]: And this is one of my favorite points from the hyponationary me episode, which is the idea that these patients with de-compsies cirrhosis, the people with portal hypertension, right?
[SPEAKER_03]: They have decreased effective circulating volume.
[SPEAKER_03]: So the body is going to be sensing that low effective blood volume, that it's not only going to turn on the
[SPEAKER_03]: And in high states of ADH, what's that ADH going to do?
[SPEAKER_03]: It's going to cause us to hold on to free water, and all that accessory water is going to lead to our good friend hyponage remia.
[SPEAKER_00]: Advanced cirrhosis usually is a state where the probability of severe hyponage remi increases, right?
[SPEAKER_00]: Sort of a compensated cirrhosis is not going to have a sort of of one 18.
[SPEAKER_00]: Not typically a decomposition cirrhosis is a high ADH state.
[SPEAKER_00]: It's a high ADHD state, so that's going to be significant human dynamic arrangement.
[SPEAKER_00]: If you have a creatinine that is 3.2 and a serum is 132 versus a creatinine 3.2 and a serum is 118, you know, I'm going to, okay, the 119 guys sounds like these are more advanced poor hypertension advanced aerosol state.
[SPEAKER_04]: The point here is if you're intravascularly depleted enough to have HRS by definition, you are also intravascular depleted enough to have high ADHD and therefore hyponotremia.
[SPEAKER_04]: So we can think of the low serum sodium as a correlate to worsening portal hypertension.
[SPEAKER_04]: And that's just the power of the serum sodium.
[SPEAKER_04]: We can get so much more information from the urine sodium.
[SPEAKER_03]: Yeah, definitely.
[SPEAKER_03]: And then I guess if thinking about A.K.I, we often get a fractional expression of sodium, A.K.
[SPEAKER_03]: the phenom, but I don't know.
[SPEAKER_03]: Is there any utility in getting that and have been portal hypertension?
[SPEAKER_03]: I mean, these patients, they're urine sodium is always going to come back less than 20, right?
[SPEAKER_03]: That portal hypertension, the patients always in this phase of deletary state, their rasses cranked up.
[SPEAKER_03]: The body wants to retain as much sodium as possible, but yeah, urine sodium is always going to come back less than 20, right?
[SPEAKER_03]: And curious, should we just ignore that FINA and just skip that part in the work up?
[SPEAKER_00]: We need to shift the threshold way down to the point that the classic cerotic is gonna have a low phenop, but in HRS is usually extremely low, almost another order of magnitude low.
[SPEAKER_00]: So that's why then I get a unit of sodium, I still like to get a unit of creatinine to get a sense of the phenop.
[SPEAKER_00]: And bottom line is that, yes, even ATN patients are gonna have low phenop, but it's probably gonna be like a point six percent, not point zero eight percent.
[SPEAKER_00]: So let's back up.
[SPEAKER_04]: We're normally a phenah of over 1% is consistent with intrinsic disease.
[SPEAKER_04]: An under 1% is consistent with pre-renal.
[SPEAKER_04]: In Cerosis, we shift this entire framework.
[SPEAKER_04]: Every phenah is going to be low.
[SPEAKER_04]: But for the AKI to be consistent with HRS, we want a phenah not less than 1%, but really something like 0.1%.
[SPEAKER_03]: Yeah.
[SPEAKER_03]: And let me just say it another way to make it stick, you know, I think we've paid attention to the decimal point and the extra zero.
[SPEAKER_03]: So if we get a phenat back for a patient who has portal hypertension and the phenat is 0.06% yes, it can be low enough to be HRS.
[SPEAKER_03]: But if it comes back and it's 0.6% in a patient with portal hypertension, then it's not HRS and maybe 80 anters of the else.
[SPEAKER_03]: Again, we're talking about a whole magnitude of
[SPEAKER_04]: To recap that, if the fina is less than 0.1%, it is virtually certain to be HRS.
[SPEAKER_04]: Something like a 0.2 or a 0.3 that doesn't really HRS out, it doesn't rule it in, but once we're talking over 0.5%, now it's extremely unlikely to be HRS.
[SPEAKER_03]: Yeah, and you know, I just thought about something, I used to work at a place where the lab, it would only come back.
[SPEAKER_03]: The urine sodium only come back less than 20.
[SPEAKER_03]: It wouldn't give us a specific number like five or nine.
[SPEAKER_03]: So I mentioned those situations, it might be like impossible to calculate macrophina.
[SPEAKER_03]: So no, what do we do in those situations?
[SPEAKER_04]: That's a great question, Traia.
[SPEAKER_04]: And to kind of calm your nerves a little bit, these urine sodium can still be helpful.
[SPEAKER_04]: If that is the case with your lab, if the urine sodium is not less than 20, then HRS is ruled out.
[SPEAKER_04]: You will not have HRS with a urine sodium greater than 20.
[SPEAKER_03]: Okay, so like we don't have the exact percentage, but, you know, at least we have some threshold to rule out each or ask whether you're in sodium.
[SPEAKER_03]: So something, I guess, is better than nothing.
[SPEAKER_03]: I'm also thinking by the cases of people who are on diuretics, how do we interpret the urine sodium in these patients with poor hypertension?
[SPEAKER_00]: And sometimes they tell me, well, the patient is still in spurino lactone, well, let me tell you, the patient is at your ass, the kidneys are not going to care if you are in spurino lactone, right?
[SPEAKER_00]: You're just not going to respond to the point of having a urinary sodium of 40.
[SPEAKER_00]: Otherwise, the kidneys are fine and respond into the diuretic, right?
[SPEAKER_00]: So, no, if the patient has a urinary sodium of 42, that is extremely inconsistent with HRS.
[SPEAKER_04]: to an HRS, all those hormonal changes make the drive for sodium reabsorption so strong that even on a diuretic, which causes you to pee out sodium, the urine sodium will still be less than 20.
[SPEAKER_04]: That's how powerful HRS is.
[SPEAKER_04]: The kidney does not care about those diuretics.
[SPEAKER_03]: That is a great point, and I guess the clinical takeaway here is that I don't have to wait until the diabetics are out of someone's system to interpret the urine sodium.
[SPEAKER_03]: So that's awesome.
[SPEAKER_03]: And so let's summarize all things about the sodium.
[SPEAKER_03]: And have had a renal syndrome.
[SPEAKER_03]: We have high age state.
[SPEAKER_03]: And so the serum sodium is going to be low.
[SPEAKER_03]: And then also in a paternal syndrome because of rases on that urine sodium will also be low.
[SPEAKER_04]: And that urine sodium isn't just going to be low, it's going to be really low.
[SPEAKER_04]: We're talking about a phenol less than 0.5%.
[SPEAKER_04]: And don't worry if the lab can only report a urine sodium less than 20.
[SPEAKER_04]: In that case, just make sure the urine sodium is less than 20, before you start thinking about HRS.
[SPEAKER_04]: Now we get to the fun and controversial part of this episode, the official diagnosis of HRS.
[SPEAKER_03]: And here we're going to talk about the idea of giving an album in challenge.
[SPEAKER_03]: And this really comes from the 2021 guidelines to diagnose who have had our renal syndrome.
[SPEAKER_03]: And this was a checklist, kind of less of five different things.
[SPEAKER_03]: One, you need to have cirrhosis with the sighties, right?
[SPEAKER_03]: That goes back to the idea of having some type of portal hypertension, the actual diagnosis of an
[SPEAKER_03]: the depths of shock, no recent nephrotoxic drugs, so no recent IB contrast, also no signs of structural kidney injury on ultrasound, and last but not least, no response in terms of the creatine after two consecutive days of diuretic withdrawal, as well as plasma volume expansion with the albumin.
[SPEAKER_04]: I don't know about you Shreya, but I don't think I've ever seen a patient who has no nephrotoxic meds.
[SPEAKER_04]: They're all on antibiotics or NSAIDs or just got contrast in the ED for a CAT scan.
[SPEAKER_04]: Yeah, that's good point.
[SPEAKER_04]: So the criteria is really hard to meet.
[SPEAKER_04]: But the general idea with this album and challenge is to roll out pre-read all.
[SPEAKER_04]: In pre-readal disease, the creatine should get better if you stop the dioretics and give albumin.
[SPEAKER_03]: right.
[SPEAKER_03]: And then if the creatine doesn't go down with Albumin for two days, then we've ruled out pre-renal and then we're really congl looking at is this more of an HRS process or an ATN process.
[SPEAKER_03]: And here is where after the 48 hours of album challenge, a year in sodium can help us differentiate between hepatorenal versus ATN.
[SPEAKER_04]: If it is true HRS, the urine sodium will remain low because high aldosterone is driving the process.
[SPEAKER_04]: If it's true ATN, the urine sodium will be high because in ATN there's tubular injury and it's not aldosterone driving the A.K.I.
[SPEAKER_03]: Too shy.
[SPEAKER_03]: Good point.
[SPEAKER_03]: And here, just to say it out loud, because we've ruled out prevenal for the two days of album challenge, things didn't get better, when you do get back that low urine sodium
[SPEAKER_03]: No, this makes me think about this idea of a two-day album challenge and I don't know about you, but I have had so many patients where I just didn't feel right.
[SPEAKER_03]: And I'm wondering, this day and age, do we have to give two days worth of albuming?
[SPEAKER_04]: And that brings us to the controversial part.
[SPEAKER_04]: This kind of one-size-fits-all approach has problems, so there's been a movement to change the way we diagnose HRS, and there's particularly there's two major changes.
[SPEAKER_00]: In 2024, in March, we published this sort of a big meeting we had in San Diego, a group of intensivists, hepatologists, and a fraudists.
[SPEAKER_00]: Let's try to revisit this definition.
[SPEAKER_00]: And the conclusion was to remove all those criteria and replace it by a statement that says that HR should be died diagnosis in the absence of a strong evidence of any other explanation.
[SPEAKER_00]: That's it!
[SPEAKER_00]: Obviously, patient can't, with fluid losses, by history, you give him alderman and gets better, boom, that's the renal, that's very simple.
[SPEAKER_00]: Well, be strong evidence of ATN.
[SPEAKER_00]: You're in our sodium above 20 or rival, that's already strong evidence against HRS.
[SPEAKER_00]: And it is feena above 0.70% that is too high, that is strong evidence of ATN already.
[SPEAKER_04]: So to reiterate, the first major change is that HRS is no longer diagnosed by that checklist.
[SPEAKER_04]: The way to diagnose HRS is just if there's an absence of strong evidence against any other explanation.
[SPEAKER_04]: That is it.
[SPEAKER_03]: Awesome.
[SPEAKER_03]: And then to recap, we do have some labs and objective clues that can clue us in and that HRS is not going on.
[SPEAKER_04]: So what would be strong evidence against HRS?
[SPEAKER_04]: We've already talked about a lot of these, a year in sodium greater than 20.
[SPEAKER_04]: That's more likely ATN.
[SPEAKER_04]: That's not HRS.
[SPEAKER_04]: If the phenos over 0.5, that's not HRS.
[SPEAKER_04]: If the story sounds pre-renal, that's probably pre-renal, so we should treat it as pre-renal and not talk about HRS.
[SPEAKER_00]: What else is the strong evidence of against HRS?
[SPEAKER_00]: Patient comes with a serum sodium of 144.
[SPEAKER_00]: What?
[SPEAKER_00]: That's not HRS.
[SPEAKER_00]: How is that going to be possible, right?
[SPEAKER_00]: Again, those are not going to be on your definition.
[SPEAKER_00]: Will you go to up to date?
[SPEAKER_00]: But I'm just giving you answering your question.
[SPEAKER_00]: Those are the things that, to me, have now been replaced by this bold statement that in the absence of strong evidence of an attempt of explanation.
[SPEAKER_03]: So to reiterate, in classic HRS, we should not be seeing normal, high serum sodium.
[SPEAKER_03]: And why is that?
[SPEAKER_03]: As a throwback, the kidneys are sensing a low volume and a battery health syndrome, 80 inches up, and that 80 is going to contribute to some degree of hyponytramia.
[SPEAKER_04]: One other thing that's really helpful is urine microscopy, specifically greater than 10 muddy brown cast per field is very likely to be ATN and strong evidence against HRS.
[SPEAKER_03]: Yeah, and then it's important to note that in real life sometimes it's not always this clear.
[SPEAKER_03]: The urine sodium sometimes is low, but then there's also some muddy brown cast.
[SPEAKER_03]: It's a really hard call between ATN versus HRS and thinking a lot of these situations we do are best to make our best gas.
[SPEAKER_04]: Yeah, sure.
[SPEAKER_04]: At HRS is tough differentiating between HRS and ATN, sometimes you're not going to know, and that's why we're here doing this podcast to try to help out.
[SPEAKER_03]: Yeah, not definitely grateful.
[SPEAKER_04]: Let's recap, Pearl 4.
[SPEAKER_04]: HRS should no longer be diagnosed by the formal checklist.
[SPEAKER_04]: The diagnosis has been replaced by a statement that HRS is the absence of strong evidence of any other diagnosis.
[SPEAKER_03]: Yes.
[SPEAKER_03]: So now, does this mean we don't have to give the album challenge every single time?
[SPEAKER_04]: And that Shreya is a great segue to Pearl Five.
[SPEAKER_04]: And this brings us to the second major change.
[SPEAKER_04]: It is no longer mandatory to give every patient 48 hour album in challenge.
[SPEAKER_03]: Oh, thank God.
[SPEAKER_03]: It just felt so wrong to do in some patients.
[SPEAKER_00]: But have a patient that comes in that was going to the hepatology clinic for frequent percentages and was requiring, as I described earlier, you know, first was once every six weeks, now is every two weeks, and now is coming every week for percentages, and shows up to the emergency room because the wife, looking at her husband, said, you look like a balloon about to explode, and it come to you the ED and they said that they have gained 13 kilograms.
[SPEAKER_00]: despite the percentages and the spiteed athletics, and you get an x-ray in a hot hydro thorax, and is got prefered demoled way to the hip and a site is and tense abdominal walledema.
[SPEAKER_00]: How will nerf you're going to give all the main challenge to that patient?
[SPEAKER_00]: You know think about it!
[SPEAKER_00]: So this is what he's having telling us historically, and this is just not an appropriate approach to just put it right on the same bucket, so if you give all of you me and close your eyes, let's come back in 40 hours, did he get better?
[SPEAKER_00]: No, that's not the approach.
[SPEAKER_00]: So my approach to our women is, in the presence of a clinical history that suggests well and depletion, or in the absence of elements that suggest ongoing hypervolemia, go for the challenge, right?
[SPEAKER_00]: And essentially, it looks right, sounds right, give our women.
[SPEAKER_00]: If the patient is overloaded, visibly to you, stay away from our women.
[SPEAKER_00]: If you're kind of in a grey zone, you're not sure?
[SPEAKER_00]: Go ahead, it's probably safe to try it.
[SPEAKER_03]: Okay, so I take away is if you have a patient who has cirrhosis, coming in with an AKI and their stories pre-read on, yeah, sure, give them albumin.
[SPEAKER_03]: But if the patient looks volume overloaded, you're worried about respiratory compromise, albumin isn't going to help them.
[SPEAKER_01]: About 8 to 11 percent of patients who get albumin with cirrhosis, have flash-formin area deema, and that's often deadly, you know, whether it's been treated per sepsis or whatever you're doing.
[SPEAKER_03]: And a quick caveat to that statistic of 8 to 11 percent of people developing flash pulmonary edema is that this population was inpatient with cirrhosis with sepsis, not HRS a little bit different, but the point is that aldeeman doesn't come without risk.
[SPEAKER_04]: Exactly, we really can't just give out aldeeman like candy to every patient with AKI, and we will talk a lot more about this in part two next week.
[SPEAKER_01]: And so knowing your patient's intrabascular volumes status before you give them extra fluids, I think it's the right next move.
[SPEAKER_01]: And so I think it's reasonable to try albumin if you're not sure or if you don't see signs of falling over load.
[SPEAKER_01]: But I think it's a little bit riskier and maybe even dangerous to just get albumin jabberbuddy.
[SPEAKER_03]: It definitely helps multiple people agree and challenge that dog love giving albumin for two days and everyone with questionable hepatorenal syndrome.
[SPEAKER_04]: It's also really good to hear, even our experts say, sometimes it's a really hard call, whether to give albumin or not.
[SPEAKER_04]: All you could do is make your best guests on what the patient's intramascular volume status is.
[SPEAKER_03]: Yeah, definitely.
[SPEAKER_03]: And so, I guess if we do go ahead and give albumin to patients that we might not be sure, do they have a paternal syndrome is this pre-renal or something else is that play?
[SPEAKER_03]: I'm curious, do we have to wait that full 48 hours before we call it HRS and possibly start treatment that could really help them?
[SPEAKER_00]: What we said is, you give our women to a patient today.
[SPEAKER_00]: Criatin in is 2.2.
[SPEAKER_00]: And the next day is 2.3 or 2.4 or 2.5.
[SPEAKER_00]: Are you going to tell me that after giving 100 grams of argument in the Criatin and we're not, you're going to give a second day and it's going to be the inflection point.
[SPEAKER_00]: Is going to come down?
[SPEAKER_00]: No.
[SPEAKER_00]: Now.
[SPEAKER_00]: If the patient had a creatinine 2.1 and UK file remained, it came down to 1.9.
[SPEAKER_00]: Of course, give it another day and give it another day and give it maybe 72 hours.
[SPEAKER_00]: Maybe whatever it takes to get the resolution of the AKR.
[SPEAKER_00]: But the idea is that you need 40 hours to determine if a login is going to work, I don't agree with that at all.
[SPEAKER_00]: So I wanted to mention that because that has come out and some of the G.I.
[SPEAKER_00]: journals and it wasn't really agreeing with that.
[SPEAKER_04]: Those trends in creatinine are really helpful.
[SPEAKER_04]: So if the creatinine the next day doesn't budget all, and we gave a really aggressive albumin dose, then we should probably think about HRS on the sooner side.
[SPEAKER_04]: And this is important because HRS has a very specific treatment.
[SPEAKER_04]: That treatment will be the entire focus of the second part of this podcast next week.
[SPEAKER_03]: Awesome.
[SPEAKER_03]: So let's recap all things about diagnosing HRS.
[SPEAKER_03]: I think we learned in our last pearl the rules have become less rigid and we now need to prove that there isn't an alternate diagnoses.
[SPEAKER_03]: And to clarify, yes, there is a role for Albumin.
[SPEAKER_03]: And it'll help us, you know, treat pre-beenal AKI in patients with cirrhosis.
[SPEAKER_03]: But we don't have to wait the full two days to see if it works or not.
[SPEAKER_03]: If the AKI is not getting better, then your left with is this hepatorrhinal syndrome, or is it ATN?
[SPEAKER_03]: Two things that are managed completely differently.
[SPEAKER_03]: And it's going to be the urine sodium that can help us distinguish between the two.
[SPEAKER_03]: In hepatorrhinal syndrome, we're going to expect a low urine sodium, right?
[SPEAKER_03]: Eldosterone's outplay.
[SPEAKER_03]: In ATN, though,
[SPEAKER_03]: We have tubular injury, and the kidneys aren't going to reabsorb sodium, and we're going to get a urine sodium greater than 20 in ATN.
[SPEAKER_04]: And that is a wrap for today.
[SPEAKER_03]: And if you found this episode helpful, our ask is to share this with one other colleague, your team, someone else who might also get a good aha from this, because HRS can be really tough.
[SPEAKER_03]: And stay tuned for our next episode and all things have had a real syndrome treatment.
[SPEAKER_04]: I want to thank our reviewers, Dr. Tapper and Dr. Belcher, and as always, opinions expressed are our own and do not represent the opinions of any affiliate institutions.
[SPEAKER_04]: Thank you, and take care.
[SPEAKER_03]: I feel like you're yelling at people, side-toors.
[SPEAKER_03]: No, I just help us, help us, no, no, for all of us just, like, people are just up and just writing, AGI on, on the roast is have had a renal syndrome, and they are compensated.
[SPEAKER_03]: All these people, no, these decophants say they don't have slunny, you know, whatever easy on all
[SPEAKER_04]: Sorry, just be a little bit of a little bit of a little bit of a little bit of a little bit.
[SPEAKER_04]: That was great.