Time Stamps

• 00:12 Introduction and Overview of Hepatorenal Treatment
• 03:38 Vasoconstrictors Focus: Terlipressin, Norepinephrine, and Midodrine
• 12:32 Finding the Right Dose of Albumin and Knowing When to Stop
• 15:06 Volume Management: Balancing MAP, Diuretics, and Creatinine
• 21:42 Understanding the High Mortality of HRS-AKI
• 32:30 Transplant, Dialysis, or Palliation Care

Sponsor: Oakstone CME’s ACP MKSAP Audio Companion

Show Notes

Pearl 1 Terlipressin and Norepi and Midodrine Ocreotide

• The treatment of HRS is to raise the MAP. 
  • MAP goal: raise up by 10-15mmHg
  • Mechanism: Reset the hemodynamics -> improve renal perfusions 
• Approach: vasoconstrictors. By potency: midodrine octreotide < Terlipressin vs. Norepinerphine Three types of Vasoconstrictors: 
• Terlipressin 
  • CONFIRM trial : HRS reversal rate Terlipressinm (32%) vs. Placebo (17%) 
  • Mostly V1 receptor agonist (vasopressin agonist), with some V2 
  • Contraindications: if creatinine over 5, MELD over 35, ACLF grade 3, volume overload, or active ischemia   
• Norepinephrine 
  • Alpha-1 agonist, beta-1 agonist. 
  • Data limited on Norepi vs. Terlipressin; questionable less potent than Terlipressin, but with fewer side effects. 
  • Most likely requires ICU transfer  
• Midodrine octreotide
  • alpha 1 agonist, and somatostatin analogue respectively
  • least potent, in head to head trials Terlipressin is better. 
  • Would only give if contraindications to Terlipressin, or if hedging and unsure if the true diagnosis is HRS.

Pearl 2: Albumin

• Albumin
  • Only to bring patients to euvolemia. 
  • Remember a main side effect of the CONFIRM trial was respiratory compromise by giving repeated dose of albumin. 

Pearl 3 Volume Management

How do you incorporate diuretics into HRS management?  

• Lasix
  • “No BP no PP”
    • Before managing volume status the first thing to do is to raise the MAP. 
    • Once the MAP has been raised by 10-15 it is safe to introduce lasix to help with volume overload. 
  • Diuretics won’t necessarily hurt the AKI, i.e. put back into HRS. 
  • Mild elevation of creatinine is acceptable if patients’ clinical status is improving. 

Pearl 4 Transplant 

How should you think through dialysis and transplant in HRS?

• For transplant candidates 
  • Dialysis can act as a bridge to transplant 
  • Liver transplant allocation is based off MELD 3.0 (INR, bili, cr, sodium, gender, albumin)
    • The kidney is very likely to function normally after a liver transplant. 
  • To be considered for simultaneous Liver Kidney transplant you must be on dialysis for at least 6 weeks, or have a GFR under 60 for at least 90 days prior to dialysis start.
  • There is a safety net for those that don’t meet dual-organ criteria, so if the kidneys don’t recover after liver transplant, you get priority at the top of the kidney transplant list. 

Pearl 5 Palliative care 

How should you approach palliative care in HRS?

• For patients who aren’t transplant candidates 
  • The question is whether to pursue chronic dialysis, knowing it won’t reverse the liver disease or pursue comfort care. 
    • With dialysis the expected lifespan is a few months
    • Without dialysis the expected lifespan is days to weeks.
  • Unfortunately, BP may too low to even tolerate dialysis, and dialysis isn’t an option 
• Of course, early palliative care involvement is best 

Transcript

Dr. Shreya Trivedi:  Welcome to the Core IM 5 Pearls Podcast, bringing you high-yield evidence-based pearls. I am Dr. Shreya Trivedi, and I am joined by…

Dr. Noah Markewitz: Hi! I am Dr. Noah Markewitz, a PGY-3 internal medicine resident at Montefiore in the Bronx. Todays episode is part 2 of our 2 part series all about Hepatorenal syndrome. 

Dr. Shreya Trivedi: If you haven’t already please go back and listen to our last episode on all things diagnosis. 

Dr. Noah Markewitz: Today’s episode will be all things treatment.

Dr. Shreya Trivedi:  And let’s remind ourselves who our wonderful discussants are…

Dr. Marina Serper: Hi, I am Marina Serer. I am a hepatologist at the University of Pennsylvania.

Dr. Juan Carlos Q. Velez: Hi, I am Juan Carlos Velez. I am a nephrologist at Oschner Health in New Orleans.

Dr. Nikhilesh Mazumder: My name’s Nik Mazumder. I’m one of the transplant hepatologists here at University of Michigan. 

Dr. Shreya Trivedi: Lets get into the 5 pearls we will be covering today. Remember to test yourself, because the more you test yourself the deeper your learning gains. 

Dr. Noah Markewitz: Pearl 1 Vasoconstrictors

Dr. Shreya Trivedi:  What are the three vasoconstrictors used to treat HRS? 

Dr. Noah Markewitz: Pearl 2 Albumin

Dr. Shreya Trivedi:  What role does albumin have in treating HRS?

Dr. Noah Markewitz: Pearl 3 Volume Management 

Dr. Shreya Trivedi:  Is it safe to give diuretics to someone who is in hepatorenal syndrome? 

Dr. Noah Markewitz: Pearl 4 Transplant 

Dr. Shreya Trivedi: How should you approach dialysis and transplant in a person with HRS?

Dr. Noah Markewitz: Pearl 5 Palliative care 

Dr. Shreya Trivedi:  What are the difference options when it comes to palliative care for someone with HRS?

Pearl 1 Vasoconstrictors

Dr. Noah Markewitz: Okay so what’s the main goal for treatment for HRS? Big picture wise, our goal is to raise the Mean arterial pressure or MAP. This is done with vasoconstrictors.

Dr. Shreya Trivedi: Wait I’m confused, we spent so much time last episode saying how the problem in HRS is too much renal vasoconstriction. Now we are saying the treatment is to give vasoconstrictors?? Something is not adding up here.

Dr. Juan Carlos Q. Velez: A question that I often get is, how is on earth is a vasoconstrictor fixing a vasoconstrictive pathogenesis? Well, because once you restore systemic arterial blood pressure, number one, that is going to override the renal perfusion pressure. And number two, you’re resetting what is actually causing the local vessel constriction in the kidneys in the first place. That’s why the renal perfusion actually improves and they are experimental and translational data showing that that’s the case.

Dr. Shreya Trivedi: Okay so giving vasoconstrictors gets the baroreceptors and gets the kidney to once again sense good pressure and volume. This reverses the cascade that led up to that vasoconstrictor in the first place.

Dr. Noah Markewitz: That’s exactly right, Shreya. And the data shows that we should aim to raise the MAP  by about 10-15 mmHg.  A 2023 study that Dr. Velez worked on took 77 HRS patients and looked at the change in MAP with vasoconstrictors. When divided into 3 groups (MAP raised by 5-9, 10-14, and 15 and above) the higher the increase in MAP the better the patients did. 

Dr. Shreya Trivedi: Since we spent time in the first episode how to differentiate HRS vs ATN vs pre-renal. Just to say it out loud, vasoconstrictors are only the Rx for HRS with the goal restore the MAP to try and reset the hemodynamics. But that’s not the case pre-renal AKI will resolve with some kind volume expansion like albumin, there is no need for vasoconstrictors. And for ATN patients, treatment is just supportive care, no role for vasoconstrictors. 

Dr. Noah Markewitz: With that understanding, now lets talk through the 3 treatment options we have to raise the MAP and try and reverse HRS.

Dr. Marina Serper: We’re going to start with most potent and then we’re going to finish up with the tried and true, but least potent. So terlipressin number one is the most potent agent, but the one that we’ve in the United States have the least experience with. So terlipressin is a vasopressin agonist. It acts on the V1 receptors, it causes splanchnic vasoconstriction. It was approved in the United States in 2022, but has been used in Europe for many, many years. So the pivotal data in the United States for terlipressin comes from the CONFIRM trial. So in the CONFIRM trial among patients with HRS-AKI, 32% of patients who received terlipressin plus albumin had HRS reversal versus 17% with albumin alone. And they were less likely to require renal replacement therapy at 30 days or have recurrence of HRS-AKI. But they had a lot more respiratory events and there’s never been demonstration that 90 day outcomes have improved. 

Dr. Noah Markewitz: So the CONFIRM trial not only showed terlipressin raises MAP, but also put Terlipressin on the MAP as one of our best agent for HRS. 

Dr. Shreya Trivedi: I see what you did there. With the MAP pun, yes putting terlipressin on the MAP!

Dr. Noah Markewitz: We saw less need for dialysis and reversal of HRS in 32% of patients who got terlipressin + albumin vs. only 17% with albumin alone. 

Dr. Marina Serper: The main side effects of terlipressin are diarrhea, volume overload, cardiovascular ischemia. Less common side effect is limb ischemia, which I have seen clinically. It’s a splanchnic vasoconstrictor, so it shunts blood from the splanchnic vasculature to the central circulation. So increases your preload and then it also increases your SVR systemic vascular resistance. So it increases your after load. And then albumin adds to that too because it increases your plasma oncotic pressure. So patients who are already volume overloaded or almost volume overloaded or have coronary ischemia, they’re at significant potential risk of compromise and side effects with terlipressin  So I think under understanding the physiology is really helpful.

Dr. Noah Markewitz: So what type is ischemia is enough for someone to hold off on terlipressin? One of our peer reviewer, Dr. Belcher, told us his practice is that anyone with active coronary artery disease or known, untreated ischemia should avoid terlipressin. If they have CAD and were stented in past and have done fine since, terlipressin is probably safe. But the thing you always need to keep in mind is that these patients have an extremely high short term mortality if HRS is not reversed, so some risks you might not take elsewhere are worth it here.

Dr. Marina Serper: And then another pearl is creatinine greater than five meld score greater than or equal to 35. So really high meld scores or grade three ACLF, that’s essentially multiple organ failures. You don’t really get a lot of bang for your buck with terlipressin. It’s kind of too late in that scenario. So we don’t usually start that that’s associated with higher mortality.

Dr. Shreya Trivedi: Okay so no terlipressin if the kidney disease is really bad – Cr over 5, or grade 3 acute on chronic liver failure aka high MELD scores. Then terlipressin is a no go.

Dr. Noah Markewitz: So thats terlipressin, second up in terms of potency is norepinephrine.

Dr. Marina Serper: So norepinephrine tried and true vasopressor, right, we use in the ICU all the time, very potent, has good evidence, decent evidence, I would say in HRS. So the mechanism, it is alpha one agonist causing vasoconstriction, beta one agonist causing increased cardiac output.

Dr. Shreya Trivedi: So norepi is an infusion typically requires ICU transfer, which can be difficult depending on how comfortable nurses feel with an infusion on the floors and might make you think about terlipressin more depending on where physically patient is.

Dr. Noah Markewitz: You know it makes me wonder if we have data to really compare the terlipressin vs. NE since they’re used in different areas.

Dr. Marina Serper: Data are limited in terms of norepinephrine versus terlipressin, but I think looking at meta-analysis, retrospective studies, norepinephrine is probably less potent probably and has also fewer side effects. On the other hand, I have to say that if I put on my research hat, it’s very difficult to conduct high quality studies in these kinds of populations that are very sick. Norepinephrine is used often as a vasopressor in the ICU for multi-organ failure. So I don’t know that I’ve seen good apples to apples comparisons.

Dr. Noah Markewitz: That makes a lot of sense. These studies might be hard to operationalize. And lets talk about our last vasoconstrictor: midodrine, octreotide.

Dr. Marina Serper: So midodrine selective alpha one agonist and then octreotide inhibits the release of glucagon and helps also with the splanchnic vasodilation. And actually after I’ve dug into the literature, we really, especially now, I think we use it to make ourselves feel better and it does increase your MAP, so you can increase your MAP with midodrine, but it’s just not as potent of a vasoconstrictor cocktail. And definitely enough studies have been done with terlipressin versus MAO midodrine octreotide albumin, and it’s clear terlipressin is much more potent.

Dr. Shreya Trivedi: So it seems like we should always try and reach for Terlipressin in terms of potency. But if the patient meets any of the contraindications for Terlipressin you should use midodrine octreotide combo. 

Dr. Noah Markewitz: A more controversial point would be if you are hedging and not entirely sure about the diagnosis of HRS. Here it is probably safer to start with midodrine octreotide since it has less side effects. 

Dr. Shreya Trivedi: Thats fair and important point. So to summarize pearl 1, the goal is to raise the MAP by 10-15 mmHg. And, Noah, lets summarize the VC in the reverse order. To cement it a different way.

Dr. Noah Markewitz: Midodrine octreotide is the least effective but has the least side effects. So if you aren’t entirely sure if it is HRS you can start here. If you are seeing a rise in MAP with midodrine octreotide alone, you should continue it. But if you’re worried its not working, then you need to escalate.

Dr. Shreya Trivedi: And what do you escalate to and that might be terlipressin or NE depending on where the patient physically is. For terlipressin, was CONFIRM trial that put terlipressin on the MAP with more reversal of HRS and less need for dialysis. There are contraindications to terlipressin though and those are Cr over 5, if they have ACLF grade 3, signs of volume overload that would risk respiratory compromise, or any signs of active ischemia.  

Pearl 2 Albumin: What role does albumin have in treating HRS?

Dr. Shreya Trivedi: Okay I think I have a handle on the vasoconstrictors. What about albumin? Sometimes we give albumin with one of the 3 vasoconstrictors, sometimes we don’t?

Dr. Nikhilesh Mazumder: I only give albumin to achieve euvolemia on day one or two or however many days you think. And then if there’s some other reason to use albumin, I will like they’re getting paracentesis or if we think they have SBP, we kind of go with that normal protocol unless there’s some contraindication as far as the respiratory volume status. But otherwise I don’t. And in fact, if you look at CONFIRM trial, that was one of the big criticisms was that they kept giving patients albumin over and over again. And that may have contributed to some of the respiratory failure outcomes as well. 

Dr. Noah Markewitz: In the CONFIRM trial 14 percent of patients in the terlipressin + albumin group had respiratory failure vs. 5 percent in the albumin only group. 

Dr. Shreya Trivedi: That is wild to think about – in terms of the amount of respiratory failure with the combo terlipressin + albumin, 

Dr. Noah Markewitz: Yeah and 17 patients in the terlipressin group died of respiratory failure vs. only 1 in the albumin alone group. I think what really came up in the journal clubs was terlipressin really the problem or was it that they were continuing to give albumin with the terlipressin and that was what pushed patients over the edge in terms of their volume status.  

Dr. Shreya Trivedi: Or was it that in the trial they just giving albumin with 1 g/kg on day 1 with a maximum dose of 100g and 20-40g/day thereafter. Not kind of defining an end point.

Dr. Noah Markewitz: I think it is important to say that technically all the trials and guidelines would recommend vasoconstrictor plus albumin, but the conversation is becoming more nuanced. We saw that using terlipressin + albumin literally killed people through respiratory distress, so we need to be careful and not just blindly give every patient albumin.

Dr. Shreya Trivedi: Yeah and it sounds like different people have different practices. Dr. Mazumder’s practice is not always give albumin and only give it to get that patient to euvolemia. In terms of how much albumin to give to reach “euvolemia” obviously there are so many practice patterns but for some its 1g/kg/day up to 100g day. Alright Noah why don’t you summarize what you want people to takeaway when it comes to giving albumin in HRS.

Dr. Noah Markewitz: Yeah its small but important takeaway, in HRS, just give albumin only use it to achieve euvolemia and then stop!

PEARL 3: How do you incorporate diuretics into HRS management?

Dr. Shreya Trivedi: Alright, now lets talk about volume management. Really this is the stuff we are humming and hazing about on rounds. And the stakes are high and sometimes the answer isn’t clear cut and I really appreciating having space to pick the discussants brain on their practices and some of their rules of thumb.

Dr. Noah Markewitz: First thing I wanted to gauge from our discussants was if and how they give lasix for HRS patients that are grossly volume overloaded. 

Dr. Juan Carlos Q. Velez: Many of these patients arrive hypervolemic if you give them diuretics before the vasoconstrictor, some diuretics just don’t work. Why? Because remember that no BP, no pee pee, if you don’t have good hemodynamics, your diuretics are not going to kick in. So once you restore the hemodynamics, not only you are treating HRS, you are going to enable successful diuresis. But of course there was this concern, wait a second, you give diuresis, you’re going to throw the patient back into HRS. So what we decided to do is to look at those patients. What was the observation? We have about 20 plus patients in this cohort. Very small cohort of course, but it was a very specific observation that we were targeting. And first of all, addition of intravenous furosemide high doses like 160 q12, something like that, to norepinephrine led to a substantial rate, a rise in urine output from somewhere in between 800 mLs a day all the way to over two liters a day. So it worked in terms of a diuretic effect. Fine. The next step is what happened with the trajectory of the creatinine? Well, the trajectory of creatinine remained unchanged. In other words, whatever was happening with the creatinine prior to the diuretic continue to happen with the diuretic. So we’re not claiming that diuretics improved kidney function, help their recovery, nothing of that nature. But what we observe is that the diuretics did not have a negative impact in the course of AKI. So it doesn’t put you back into HRS. That’s kind of the observation. So I think we have to move a little bit away from this albumin albumin approach, and then we start thinking to a more balanced where yes, some patients should be treated with albumin aggressively, some patients don’t need any of the albumin, nothing at all. And some patients may actually need to be diuresed. 

Dr. Shreya Trivedi: Okay, wow so much to unpack there. I really appreciate all the nuance. When I step back, when it comes to HRS we really need to understand the person in front of us in HRS and figure two big Qs: what we are going to give to raise their MAP by 10-15 mm Hg and then in addition is albumin right or diuresis right or neither?

Dr. Noah Markewitz: Classic to come up on rounds. And just I felt relieved to know that once you  successfully raised the MAP by 10-15 then there is evidence that it is safe to give diuretics if the patient needs it.

Dr. Shreya Trivedi: I think it was also helpful to hear if you give diuretics too early, it won’t cause any harm, but the kidney just doesn’t have the BP to successfully make urine. So try and get that BP up first or as the cool kids, or as the nephrologists say, get the BP up before you can get some pee pee. 

Dr. Noah Markewitz: I am glad someone thinks the nephrologists are the cool kids!

Dr. Nikhilesh Mazumder: I think the most common hesitancy, which is real is the creatinine number. But it’s not as important as the patient’s status. And so the physical exam and volume exam I think is one of the most important things that distinguishes an internal medicine doctor from other physicians and medical providers. And I think that treating patients, as you alluded to based on diuresing them if they’re volume overloaded or providing fluids if they’re not sure otherwise, I think is one of the most counterintuitive parts when the creatinine is rising. And I wouldn’t jump to diuresis unless the patient really needed it, but I wouldn’t hold it if the patient did need it because the creatinine was elevated. We see this often in the outpatient regimen area where we start them on some diuretics and their creatinine goes up by 0.2 or 0.3 or something, but the ascites is totally under control. They’re not requiring paracentesis. But if you’re crimping down on the kidneys a bit and the creatinine’s going up and it’s benefiting the patient from a clinical perspective, I think that’s one of the biggest things I’ve learned in fellowship and going into being an attending is that 0.2, 0.3 of creatinine might be worth it if it’s providing some clinical benefit to your patient. And so it may not be worth it if they’re still getting paracentesis every week and you’re not really changing anything. But in those patients who can kind of move the needle on their quality of life or the bad things that are happening to them, I think that’s one of the most common areas in which I help is I am comfortable just saying, no, we’re just going to keep on diuretics. 

Dr. Shreya Trivedi:  So this is giving me flash backs to our cardiorenal syndrome episodes. It is okay for permissive hypercreatininemia if the patient is clinically improving. Noah do you wanna try to summarize volume mgmt in HRS which of course is nuanced and very different case by case?

Dr. Noah Markewitz: I will take a stab at it! The first thing to do is raise the MAP. You aren’t going to get good diuresis without BP. And once you have successfully raised the MAP we do have some data that we won’t put the kidneys back into HRS with diuresis. We might have to be okay with some permissive hyper-creatinemia and prioritize clinical volume status if the patient needs it.  But as we have been saying. This is really hard an nuanced and we need to just do the best with what we think the patients volume status is.

Pearl 4 Transplant: How should you think through dialysis and transplant in HRS?

Dr. Shreya Trivedi: So we talked about treatment now, lets talk  about when things aren’t going as well as we’d want with treatment. And brings to mind that high mortality rate and I think First and foremost, to be on the same why the mortality in HRS so high?

Dr. Marina Serper: Why is mortality so high in a great, I actually really love that question. So because we have the portal hypertension physiology, so we know we have a very hard liver for the most part we have portal hypertension and that comes with all of this bacterial translocation predisposition to infections. And so that’s one part of it is that your liver portal hypertension plus synthetic dysfunction plus the other thing is what triggers HRS is the company it keeps so to speak. So sepsis, organ failure, severe bleeding. So that’s why the mortality is high.

Dr. Shreya Trivedi: Let’s continue with the dark side of things, what if the vasoconstrictors we choose do not work? Or we try other things and its not working?

Dr. Noah Markewitz: So we tried to prevent renal failure in hepatorenal syndrome but the Cr is still rising,  potassium is 6 despite potassium binders, the patient has not peed in 2 days. The next thing to ask yourself about is is patient a liver transplant candidate. And because the “vasoconstrictors not working in hepatorenal syndrome” means we likely hit one or two of the AEIOU indications for dialysis, and now we have to think about is can we use dialysis as a bridge to transplant?

Dr. Shreya Trivedi: That makes sense and as a connection from episode 1, we learned that most of the time in HRS the actual kidney is fine so the dialysis here is temporary, right? Once a patient gets a liver and the good blood flow is restored to the kidney, the kidney will get back up and do its thing like the olden days. 

Dr. Noah Markewitz: So I am fascinating by the ethics of liver transplants but thats a whole other episode but we have to remember that its really the MELD that determines a liver transplant priority.

Dr. Marina Serper: So the new MELD score is the MELD 3.0, which is your total bilirubin, your INR, your creatinine sodium, and now albumin and also sex because women were disadvantaged because women have a lower muscle mass, they have lower creatinine for GFR and there were some other issues. So that’s the MELD 3.0. So creatinine has a pretty hefty weight in the MELD 3.0 and the MELD score to remind everyone prioritizes people on the liver, for the liver transplant wait list based on likelihood of mortality. So it’s urgency based prioritization. So the worse your AKI, the higher your creatinine, the higher your liver transplant priority, and that’s because your mortality is high. But there’s a paradox here that if we get your kidney function better, your MELD score will improve and then you were very ill at one point, but you’ve lost your MELD points, right? So this is a little bit nuanced, but in the United States, if you’re a MELD score is above 25, you have to update that MELD score every seven days. So if you imagine someone comes with an AKI creatinine of 3 and then they’re on terlipressin and then they improve and a week later their creatinine is 1.5, their MELD score went down and their priority is lower. Is it possible that some people withhold terlipressin in this setting potentially when the MELD is really high because you know that the most durable treatment for this patient is actually transplant?

Dr. Noah Markewitz: Ugh, as I just said the ethics of transplant are a thing in its own. It gets complicated so fast.

Dr. Shreya Trivedi: That makes me think, if Cr is part of the MELD score, if you are on dialysis, won’t change your Cr and effect your transplant candidate priority? 

Dr. Marina Serper: So if you’re on dialysis, it’s as if your creatinine is three. It’s the same thing. So you get the biggest benefit for kidney injury if you’re on dialysis. And even if you have extremely low muscle mass and your creatinine is only 1.5 or 2, you’re still going to get the maximum points if you’re on dialysis.

Dr. Shreya Trivedi: Okay, so dialysis gives your patient the most points when it comes to Cr. So, we’re okay there.

Dr. Noah Markewitz: I just think transplants are so cool and what’s even cooler is we have the ability to replace two organs at the same time! 

Dr. Shreya Trivedi: Two organs? Yeah two organs you mean the liver and kidney –  But why would they need a kidney? We just said kidneys are often fine in HRS?  

Dr. Noah Markewitz: Yes true but the longer HRS goes on, the more likely it is that the kidneys won’t recover. It is also important to think about patients who started off with some baseline chronic kidney disease, those scarred kidneys, probably won’t recover. You can look at our show notes for when to do a simultaneous kidney and liver transplant. 

Dr. Shreya Trivedi: What is the patient gets a liver but the kidney doesn’t recover?

Dr. Noah Markewitz: Whats nice is there is something called the safety net.  The safety net moves  the patient who only got a liver to the top of the kidney transplant list if their kidney doesn’t recover after the liver transplant surgery. 

Dr. Shreya Trivedi: I am glad they have this all in place. So lets summarize this pearl. For liver transplant we base it off the MELD which is very heavily dependent on how the kidney is doing. The big takeaway for me these patients will often need dialysis as a bridge to liver transplant. And the criteria to pull that trigger is the same with any new dialysis: AEIOU criteria. And because with a liver transplant, we expect the kidneys to recover just fine, we don’t always need to jump to a simultaneous liver kidney transplant and prioritize the liver transplant first. 

Pearl 5: How should we involve palliative care in HRS?

Dr. Shreya Trivedi: Okay lets really get to the real dark side of things, if someone isn’t a liver transplant candidate, say they have active extra-hepatic cancer or don’t have the social support to be able to come to appointments and get labs for the immunosuppressants they’ll be on after the transplant.

Dr. Marina Serper: That’s when we have to think about goals of care discussions. If the patient is not on a liver transplant list and they have rapidly progressive renal injury that requires dialysis with no ability to reverse the underlying liver physiology. This is where I strongly believe we should involve palliative care because we don’t really have dialysis as a bridge to an improvement. 

Dr. Noah Markewitz: What an impossible situation. Do we pursue dialysis for this patient, knowing that there aren’t any options to fix the liver, and they are going to die even with dialysis? 

Dr. Shreya Trivedi: Yeah, it seems like dialysis here would feel like a very temporary bandaid and for how long and what quality of life?

Dr. Marina Serper: And I do try to be frank, very frank from a liver standpoint and explain that this is what’s going on with your liver. This is how we would treat the liver problem. And transplant normally could be a way that we would treat this, but however, in this scenario we cannot do liver transplant for X, Y, Z reason. And then I explained, so in the case of let’s say HRS-AKI and other sepsis decompensation and the need for dialysis, let’s say, I explained that putting them on dialysis will generally not improve the sepsis, will not resolve the liver dysfunction. And so that’s not something that will help them get back to where they were. So I think it’s better to try to get on the same page. Honestly, outline expectations. And explain what medically is feasible versus not. And I know that some people like the best case scenario, worst case scenario rubric, right? Best case scenario, your infection gets treated and you get a liver transplant. That works if somebody could be a transplant candidate. And worst case the liver gets worse and transplant’s not on the table, that’s useful. But some people don’t necessarily have a scenario where the best case is returning them to prior function. So best case could be being symptom free, being with family. So you really have to be honest and upfront and it’s not always a menu of good options.

Dr. Juan Carlos Q. Velez: So if the patient is able to tolerate a session in the hospital and you can prepare them for a clinic, then you’re going to have to explain, okay, so the expectation is that we don’t do dialysis. Your survival may be days, just as an example, but if we do dialysis, your survival may be three months, six months. It’s not that we’re going to gain a two year. Unlikely, right. So you present that to the patient and sometimes that is a meaningful extension of their lives because they need to go home, they need to get their family together and they need to process that. Right? 

Dr. Shreya Trivedi: So heavy to hear but helpful. Helpful to hear that without a liver transplant in HRS, dialysis might only buy them a 3-5 months or so.

Dr. Noah Markewitz: For me, I really love the best case worst case frame work. Sometimes patients need to know that their best case even WITH dialysis may not involve being independent enough to say, take a walk in the park. Even WITH dialysis some patients’ best case may be just getting medicine to control symptoms while they are with family as long as possible until they peacefully pass away. 

Dr. Shreya Trivedi: Unfortunately, it can get even trickier when patients can’t tolerate dialysis.

Dr. Nikhilesh Mazumder: One of the tricky parts about offering everybody dialysis is that if they’re very hypotensive, because they’re kind of end stage portal hypertensive patient, often they won’t tolerate dialysis, for example, they put the catheter in, you attach into the machine and their blood pressure will be too low for them to actually get dialysis. So on paper, they’re on dialysis, but physiologically or biochemically, they’re not really getting cleaned by the machine or getting volume removed.

Dr. Shreya Trivedi: You know when he said that I was like wow why didn’t think of that earlier. These patients might not being able to tolerate dialysis. So the patients get tubes put in their body, hoping dialysis will help and get connected to these machines but cant even tolerate it.

Dr. Noah Markewitz: I agree, Shreya it is a very humbling thought. So to recap if liver transplant is not in the cards, unfortunately, the option is a few months dialysis or just comfort care for a week or two if dialysis is not within their goals. I’m really sorry to end the podcast on a very depressing note but I think really good palliative care is rewarding in itself and its really important to take ownership of this aspect of HRS too. Its also important in taking ownership for helping patients transition to their death.

Dr. Shreya Trivedi: Yes, hepatorenal syndrome is not for the faint of heart at all. Its such tough disease process with mortality that is so high and I think we did right by spending a bunch of the time on the dark side and hopefully we can help our patients sit through it if should they come to that crossroads.

Dr. Noah Markewitz: And that’s a wrap for today.

Dr. Shreya Trivedi:  And if you found this episode helpful, our ask is to share with your team and colleagues and share it with someone else because HRS can be tough! 

Dr. Noah Markewitz: Thank you to our reviewers, Dr. Tapper and Dr. Belcher. As always, opinions expressed are our own and do not represent the opinions of any affiliate institutions. Thank you and take care!

References

• Velez JCQ, Karakala N, Tayebi K, et al. Responsiveness to Vasoconstrictor Therapy in Hepatorenal Syndrome Type 1. Kidney360. 2023;4(4):e448-e456.
• Wong F, Pappas SC, Curry MP, et al. Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome. N Engl J Med. 2021;384(9):818-828.
• Velez JCQ, Wickman TJ, Tayebi K, et al. Addition of a Loop Diuretic to Norepinephrine During Treatment of Hepatorenal Syndrome Type 1. Kidney Int Rep. 2024;10(2):466-474. Published 2024 Nov 19.
• Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74(2):1014-1048.