Cardiorenal Considerations: 5 Pearls Segment

Core IM Podcast

Time Stamps

• 02:05 Pearl 1: Make sure the renal dysfunction is not from something else
• 08:47 Pearl 2: Practical tidbits on loop diuretics
• 18:08 Pearl 3: Assessing diuretic response
• 27:35 Pearl 4: Approaching diuretic resistance
• 35:08 Pearl 5: Don’t be afraid of medical therapy because of CKD

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Show Notes

Pearl 1: Make sure the renal dysfunction is actually all cardiorenal!

• How do you define cardiorenal physiology?
  • Classic Definition:
    • Kidney dysfunction that is related to either a (1) low-flow state and/or (2) renal venous congestion
      • BOTH can independently lead to decreased intrarenal blood flow
      • BOTH can lead to neurohormonal activation → Increased renin-angiotensin-aldosterone system (RAAS) activity
        • These are compensatory mechanisms that initially preserve renal function but can become detrimental when kidney autoregulation can no longer compensate.
      • NOTE: Renal venous congestion is thought to be a larger contributor to kidney dysfunction than low-flow states in most cases of cardiorenal syndrome.
• How should you think about the differential for a kidney injury in someone with heart failure?
  • Be broad! Multiple processes can happen at the same time
    • Urinalysis findings:
      • Pure cardiorenal syndrome
        • “Bland” with no protein, blood, granular or other cell casts
          • May have hyaline casts
          • No signs of intrinsic injury!
    • NOTE: Screen for proteinuria in heart failure patients!
      • • Urine protein to creatinine ratio (UPCR) or
        • Urine albumin to creatinine ratio (UACR)
      • Dilute urine can falsely lower proteinuria on a urine dipstick!

Pearl 2: Practical Tidbits on Loop Diuretics

• What is the “go-to” loop diuretic for someone who is hospitalized for volume overload?
  • Intravenous therapy!
    • Because gut edema may interfere with oral absorption
  • Dosing:
    • 2.5 times their equivalent daily oral home dose of diuretic
      • Benefits of this dosing:
        • Better decongestion at 72 hours
          • By weight and symptom improvement
        • Faster transition back to oral diuretics
          
          • Compared to lower IV doses
    • Continuous vs. Bolus dosing?
      • No difference in outcomes!
        • NOTE: Patients being treated with bolus may require more escalations in dosing during their hospitalization
• What are the differences between loop diuretics?
  • IV formulations:
    • Furosemide vs. Bumetanide
      • No difference in outcomes demonstrated
        • But not largely studied!
      • Bumetanide Considerations:
        • More potent
          • Practitioners may be more comfortable with using higher equivalent doses since bumetanide doses are in the single digits
        • Severe myalgias with IV bumetanide as a continuous infusion
          • Especially with higher doses
          • Unclear if unique to bumetanide or if purely dose-related given furosemide is not typically used at equally high equivalent doses
  • PO formulations:
    • Furosemide vs. Torsemide vs. Bumetanide
      • Conversions (PO): Furosemide 40 mg = torsemide 20 mg = bumetanide 1 mg
    • Considerations when choosing PO:
      • Bioavailability
        • Furosemide
          • Extremely variable bioavailability (10-100%)
        • Torsemide & Bumetanide
          • More consistent bioavailability (80-100%)
      • Duration of action
        • Torsemide (6-16 hours) > furosemide (6-8 hours) > bumetanide (4-6 hours)
          • NOTE:
            • Torsemide can be dosed once daily, whereas
            • Bumetanide should be dosed at least twice daily!
    • Torsemide is preferred over furosemide since it is more predictable!
      • Caveat: The TRANSFORM-HF trial did not show significant difference in outcomes between torsemide and furosemide
        • However, there are many criticisms of the trial!
          • Significant crossover
          • Use of mortality as the primary outcome rather than other metrics

Pearl 3: Assessing Diuretic Response and Renal Function

• How to assess diuretic response?
  • Traditional assessment:
    • • Weights
      • Exam findings
      • Urine output
    • Challenges with relying on these:
      • Inaccurate documentation and/or
      • Delay in diuretic titration
        • In case of inadequate response
  • Alternative assessment:
    • Spot urine sodium (UNa) level
      • Measures diuretic responsiveness
      • Quick assessment 1-2 hours after administering loop diuretic
      • Interpretation:
        • UNa < 50-100 mEq/L → poor response to the current dose of loop diuretic
        • GOAL: >70 mEq/L
          • For an appropriate response
        • Causes of falsely high spot UNa:
          • Low volume of urine
          • Metabolic alkalosis
          • Medications (ex. piperacillin-tazobactam)
        • Causes of falsely low spot UNa:
          • Cirrhosis
          • High volume of urine
      • NOTE: Using a spot urine sodium AND 6-hour urine output-guided protocol to escalate loop diuretic dosing was feasible
        • Resulted in:
          • Significantly higher diuresis at 2 days
          • Shorter length of stay!
• What do you do if the response to diuretic is not adequate?
  • Double your loop diuretic dose
  • Start a drip (if at maximum dose)
  • Reassess initial diagnosis or if new insult!
• What happens to creatinine during diuresis?
  • Generally safe to see up to 30% rise in from baseline levels with active decongestion
    • Known as “rise in serum creatinine” (RSC) or”worsening renal function” (WRF)
      • Usually does NOT reflect true renal tubular injury
        • Even though this threshold is how acute kidney injury (AKI) is defined
      • Rise is a result of:
        • Hemodynamic or functional change in glomerular filtration
        • Hemoconcentration of creatinine
          • In patients who are being adequately decongested!
      • Alone, should NOT be a reason to stop diuresing a volume overload patient
        • NOTE: Mortality actually worse for patient’s whose serum creatinine “improved” from baseline compared to those who had “worsening” levels.
      • The rise has no predictive value for rehospitalization or mortality unless patients also had other signs of congestion at discharge
  • Still, always still do the due diligence each day!
    • Volume assessment
    • Urine output monitoring
    • Consider need to evaluate for another cause of rising serum creatinine
    • Consider more sophisticated and/or invasive measures of volume status
      • Point-of-care ultrasound (POCUS)
      • Venous Excess Ultrasound (VExUS)
      • Right heart catheterization

Pearl 4: How to approach diuretic resistance

• What is diuretic resistance?
  • Failure to achieve therapeutically desired congestion relief despite using appropriate or escalating doses of diuretics.
• Consider…Is something else going on?
  • Diuretics cannot work if they are not reaching the kidney!
  • Some factors to consider:
    • Shock
    • Low-flow state
    • Elevated intra-abdominal pressure (ascites)
• How can you augment your diuresis?
  • Sequential nephron blockade!
    • Thiazide or Thiazide-Like Diuretics:
      • PO Metolazone vs. IV Chlorothiazide (or Diuril)
        • Metolazone
          • Less expensive
          • Metolazone has a much longer half-life and duration of action compared to chlorothiazide
        • Chlorothiazide
          • More expensive (cost is starting to come down)
          • NOTE: Many clinicians anecdotally prefer chlorothiazide because of faster onset and IV administration
        • Effect:
          • No significant difference between two in terms of urine output measured at 24-48 hours.
      • Alternative adjusts:
        • Hydrochlorothiazide or Chlorthalidone
          • Reasonable options though more in outpatient setting
          • • Commonly used as antihypertensives
        • Acetazolamide
          • Achieves successful decongestion and shortening length of stay
            • Without any differences in safety outcomes!
          • In practice: Considered especially in cases of worsening metabolic alkalosis or in COPD
            • Caution when using if there is acidosis or serum bicarbonate is low!
        • Acute SGLT2i
          • Not well-established adjunct
          • (though beneficial in general and may be safe to add during heart failure hospitalizations post-AKI)
        • Hypertonic saline
          • Not well-established adjunct
• What should be monitored during diuresis?
  • Electrolytes, particularly hypokalemia
    • More common with augmentation
    • Hypokalemia is an independent risk factor for development of diuretic resistance
      • Add potassium-sparing diuretics early!
        • Long-term benefit
  • Rapid Volume Depletion
• What about ultrafiltration (UF)?
  • CARRESS-HF Trial
    • Stepped diuretic algorithm was superior to starting with ultrafiltration
      • Preserved renal function
      • Lower rates of adverse events
    • Criticisms:
      • May not be realistic (diuresis was not attempted in UF group)
      • Unclear if ideal rate of UF was used
  • In practice: UF only after a failing maximal medical therapy
    • Due to concerns about future renal function when starting HD and dialysis access complications

Pearl 5: Don’t be afraid of medical therapy because of CKD

• Guideline-directed medical therapy (GDMT) for heart failure
  • Also are key medical therapies that slow progression of CKD!
    • Benefit of medications seen in patients with:
      • Proteinuric CKD (estimated albuminuria > 300 mg/day) with or without diabetes
    • GDMT meds are heavily underutilized in patients with concomitant heart failure and CKD
      • Despite worse outcomes!
        • Percent of patients of GDMT (RAAS inhibition, MRA, beta blocker) by eGFR at discharge
          • eGFR 30-45 → only 15% of patients!
          • eGFR < 30 → only 5% of patients!
        • NOTE: Data from 2014-2019 heart failure registry
          • Before SGLT2 inhibitors became an established pillar in heart failure and CKD
• How should you start GDMT in advanced CKD?
  • Expect an initial decline in eGFR based on creatinine
    • • When starting RAAS inhibitors and/or SGLT2 inhibitors
        • But don’t panic!
    • Decline is usually reflective of:
      • Glomerular hemodynamic changes
      • Reduction of pathologic hyperfiltration
    • Decline is associated with:
      • Better outcomes
      • Slower annual eGFR decline afterwards
        • SGLT2i studies
    • General Advice: Tolerate up to a 30% reduction in eGFR after initiation as declines in eGFR larger than 30% are unusual with these agents!
  • RAAS Inhibitors
    • Tips & Tricks
      • RAAS inhibitors should NOT be stopped solely because of declining eGFR
        • STOP-ACE Trial – no significant difference in trajectory of GFR decline or number of patients started on RRT when stopping vs. continuing RAS inhibitors at eGFR < 30
          • Signal towards worse cardiovascular outcomes, however, when these agents are stopped.
      • Hyperkalemia IS more of a reason to pause – but consider trying to treat the potassium first!
        • SGLT2 inhibitors are also protective against hyperkalemia – even more reason to have them on board if not already!
        • Consider adding potassium binders (see our episode on hyperkalemia in CKD).
  • SGLT2 Inhibitors
    • Tips & Tricks
      • Currently approved for initiation at eGFR > 20
        • EMPA-CKD Trial
        • Subgroup analyses of DAPA-CKD Trial
        • There are ongoing trials where people are being safely continued on these agents even through dialysis!
          • SGLT2 inhibitors can likely be continued safely even if eGFR eventually declines to < 20!
  • Mineralocorticoid Receptor Antagonists (MRA)
    • Tips & Tricks
      • All MRAs:
        • Improved cardiovascular outcomes and mortality
        • At least observational data that they may improve renal outcomes over the long-term
      • NOTE: It is still extremely important to closely monitor for dangerous potassium issues and kidney function especially when initiating any MRA!
      • Finerenone:
        • • New agent on the block!
        • Slows CKD progression in patients with type 2 diabetes and proteinuric CKD in randomized setting (FIDELIO-DKD)
        • Non-steroidal mineralocorticoid receptor antagonist
          • More selective for the mineralocorticoid receptor
            • Compared to more familiar agents like spironolactone or eplerenone (which are steroidal MRAs)
          • Reduced rates of hyperkalemia
            • Compared with steroidal MRAs
        • Also improves cardiovascular outcomes like the other MRAs (primarily by reduced heart failure hospitalizations)

Transcript

Dr. Nayan Arora: That’s why we created a separate cardiorenal service at our hospital, is because these patients are hard. They’re complicated, they’re difficult. They still scare me, and I’ve been doing this for years now.

Dr. Shreya Trivedi: That was Dr. Nayan Arora, a nephrologist at the University of Washington. We were so excited to have him as one of our discussants to help us through what can be a scary topic for most, cardiorenal syndrome. Welcome to Core IM 5 Pearls Podcast, bringing you high-yield, evidence based pearls. This is Dr. Shreya Trivedi. And I’m joined by.

Dr. Andrew Ling: And this is Dr. Andrew Ling, a second-year Internal Medicine resident at BIDMC.

Dr. Shreya Trivedi: Yeah, so let’s get into what we’ll be covering today. Test yourself by pausing after each of the 5 questions. Remember, the more you test yourself, the deeper your learning gains.

Dr. Andrew Ling: Pearl 1 – Make sure the renal dysfunction is not from something else.

Dr. Shreya Trivedi: What are you expecting to see in the urinalysis in a patient with AKI from purely cardiorenal syndrome?

Dr. Andrew Ling: Pearl 2 – Practical tidbits on loop diuretics.

Dr. Shreya Trivedi: What are the differences in bioavailability, duration of action, and outcomes between furosemide, torsemide, and bumetanide?

Dr. Andrew Ling: Pearl 3 – Assessing diuretic response.

Dr. Shreya Trivedi: How can spot urine sodium measurements be used to assess diuretic response?

Dr. Andrew Ling: Pearl 4 – Approaching diuretic resistance.

Dr. Shreya Trivedi: What types of agents do you think about adding to loop diuretics to augment diuresis? And in what situations?

Dr. Andrew Ling: Pearl 5 – Don’t be afraid of medical therapy because of CKD.

Dr. Shreya Trivedi: Should you stop RAAS inhibitors or SGLT2 inhibitors when the creatinine reaches a certain threshold? Why or why not?

Pearl 1 – Make sure the renal dysfunction is not from something else

Dr. Andrew Ling: Alright, Shreya. Let’s get into it with a case. You have Ms. CR, a 67 year old patient who has a history of heart failure with an EF around 40% and CKD who comes into the ED with shortness of breath and weight gain. She takes torsemide 40 mg once daily at home but she has not been urinating as much as she normally does.

Dr. Shreya Trivedi: Ah! Sounds like she could use some diuresis for that volume overload!

Dr. Andrew Ling: For sure, but her creatinine is 2.5 mg/dl from a baseline of around 1.7 mg/dl. You are feeling like it’s probably cardiorenal, and you do want to diurese, but the degree of her AKI is making your team a little queasy about just pulling the trigger and how to manage her other medications.

Dr. Shreya Trivedi: Yeah, this sounds very familiar! Especially with that creatinine being up from 1.7 to the mid 2 range. I think makes anyone really nervous.

Dr. Andrew Ling: Yeah, for sure. Let’s step back for a second – what do we actually mean when we say the AKI is cardiorenal?

Dr. Nayan Arora: We’re talking mostly patients with type one cardiorenal syndrome, which is going to be your acute heart dysfunction causing acute kidney dysfunction, right? So that’s your classic type one cardiorenal syndrome patients in the hospital with decompensated heart failure and you see that their creatinine’s up.

Dr. Andrew Ling: We also sat down with Dr. Nicole Bhave, one of the cardiologists with a special interest in the cardiorenal population at the University of Michigan.

Dr. Nicole Bhave: When we say cardiorenal, most of the time we’re referring to chronic kidney disease or acute on chronic kidney disease, um, that’s related to kidney congestion and/or a low flow state.

Dr. Shreya Trivedi: So when we have this low-flow state, I think a lot of people think about low cardiac output right? I think a lot of people get that when there is a low cardiac output that causes a prerenal AKI since the heart is not pumping enough blood forward to the kidney, but, Andrew, how do get congestion without that cardiac output problem leading to that cardiorenal picture?

Dr. Andrew Ling: That’s a great question, Shreya, that I was looking into a little more. So when we talk about congestion, there is extra pressure on the venous side of the renal capillary bed, kind of where the blood is leaving the kidney. That venous congestion makes it more difficult for blood to travel through the kidney itself, and the exit for the blood on the venous side gets jammed up.

Dr. Shreya Trivedi: Okay, so in cardiorenal syndrome, even when your heart is giving you a good output and forward flow, just having backup and higher pressures on the venous side can also block how much blood is actually making it through the kidney and that may be more the driver.

Dr. Andrew Ling: Right, and I think this is an important point because at least when I learned about AKI in heart failure, back in med school, the focus was on the heart not getting enough blood forward to the kidney. But actually, the forward flow is often fine and really it’s the venous congestion that is probably more important. And our reviewers emphasized that the relationship may be bidirectional – depending on the case, it can be either the heart or the kidney, or maybe something else entirely thats effecting both organs in parallel. That be driving this cardiorenal syndrome.

Dr. Shreya Trivedi: It’s really good to get that pathophys backing. Why don’t we go back to Ms. CR, Ms. Creatinine. Her creatinine is going up, she has some cardiorenal physiology, either from venous congestion or maybe poor forward flow also contributing. Either way, how can we feel sure about this? Except for getting a good volume exam, which, bless everyone’s soul, trying to do. What else can make us feel sure?

Dr. Nayan Arora: So what you’re looking at is classic cardiorenal syndrome is going to be you get your urinalysis and it’s bland. You don’t have protein, you don’t have blood. You can have hyaline casts and that can actually help support that diagnosis, but you’re not going to have granular casts, red cell casts, other things. There’s no rule that says you can’t have two things at the same time. So you could have cardiorenal syndrome superimposed on other things. People can come in with tubular injury, maybe they’re in cardiogenic shock and they’re hypotensive and they have a hypoperfusion injury to the kidney. Maybe somebody gave them antibiotics a week or two ago and they have interstitial nephritis. Maybe they got that cardiac cath a while ago and they have atheroembolic disease.

Dr. Andrew Ling: So sounds like when we see a Cr up in someone with HF, we should ask am I dealing with just cardiorenal syndrome? Or am I dealing with an intrinsic renal process or something else entirely?

Dr. Shreya Trivedi: Right, I think it’s so easy once an AKI or a CKD label is in a one-liner to not go back and rethink other insults.

Dr. Andrew Ling: Right, and even the simplest thing that we can forget in a busy clinic day or ER visit to chart review to see if we ever got a UA on the patient before or urine albumin-to-creatinine ratio.

Dr. Nicole Bhave: One of my patients, who I’ve been taking care of for a long time has coronary disease and heart failure with mildly reduced ejection fraction. And his creatinine had been sort of creeping up over the years and it was one of these things where I went back and said, oh, I’ve taken him for five years and his creatinine was 1.5 and now it’s closer to two. And I was really kind of wondering, like, I had been, again, thinking that it was all cardiorenal and then I got a urine sample and he had, he had proteinuria and he actually, um, went on to have a biopsy and had FSGS, and now is on, now is on PD.

Dr. Shreya Trivedi: Wow, now that’s a case I’ll remember! Imagine finding FSGS kind of out of nowhere?

Dr. Andrew Ling: It is kind of wild! And I think an important reminder for us too, Shreya, is that the common chronic risk factors for heart disease – things like hypertension, diabetes, vascular disease – are also the same common risk factors for intrinsic chronic kidney disease. So there’s a lot of reasons for these patients to have something else going on.

Dr. Shreya Trivedi: So to recap, in classic cardiorenal syndrome, there will be no signs of intrinsic kidney injury aka there is going to be a bland urine. Hyaline casts are okay, but there should be no new protein, blood, or other cells in the urine if the AKI is completely cardiorenal.

Dr. Andrew Ling: Right, and of course there are those people with transient proteinuria where you may want to at least repeat the urine albumin or leave it as a transitional issue for the outpatient setting. But don’t let it be something that fall off your radar! It may be a sign of some other intrinsic process going on which can really change someone’s management, especially as an outpatient.

Pearl 2 – Practical Tidbits on Loop Diuretics

Dr. Andrew Ling: Alright so let’s get back to Ms. CR. You get the urine and it’s pretty bland (and again meaning no blood, no cell casts, no protein). She seems volume overloaded on your exam but thankfully not cool or looking like a patient with really low output in cardiogenic shock.

Dr. Shreya Trivedi: Yeah, so since she is volume overloaded, we should probably give her diuresis to help her feel better and get blood moving better through those kidneys. So let’s get into practical tidbits on IV diuretics and then move onto oral diuretics after.

Dr. Andrew Ling: So, I know based on the DOSE Trial, we can feel safe with an aggressive approach of taking her home diuretic dose and give 2.5 times that amount by IV dosing per day while she is in the hospital. For Ms. CR, shes on torsemide 40 mg at home, so that would be aiming for 200 mg IV Lasix throughout the day.

Dr. Shreya Trivedi: Alright so with that 200mg IV lasix, should it be broken up into boluses or a drip. I’m curious about what our experts had to say on which one may be better?

Dr. Nayan Arora: No study has really shown a difference between the two. I have my own reasons for liking bolus dosing more. I mean, I think it gives the macula densa a bit of a break, but again, that’s personal preference.

Dr. Shreya Trivedi: Oh! I like the sound of that, giving the macula densas a break. We all need a break from time to time! I can get behind that.

Dr. Andrew Ling: Yeah! For sure, and I feel like the classic situation, here, is one attending sticks with bolusing and then the next one takes over and says alright start the drip. Good to know there’s no actual difference that’s been shown.

Dr. Shreya Trivedi: Right, a dealer’s choice from bolus or drip. Aright, what about the actual IV diuretic options. How do we think through those?

Dr. Nayan Arora: So in the hospital, pick your IV medication. So torsemide is oral, so generally you’re probably going to go with an IV option when somebody needs more acute therapy. I personally don’t think there’s any difference in IV furosemide or IV bumetanide except for that the IV bumetanide allows people to use higher doses of loop diuretics than they’re comfortable with IV furosemide.

Dr. Andrew Ling: You know, Shreya, I tried reading into why people feel more comfortable with higher equivalent doses of IV bumetanide. It wasn’t really clear to me whether it’s just that the doses that have been approved for bumetanide are in the single digits. Maybe it feels unsettling to give people doses of Lasix in the several hundreds.

Dr. Shreya Trivedi: Yeah, I think its a psychological thing! The numbers can definitely fool us but we have to remember the relative potencies which we’ll hopefully lay out in our infographic, that we’ll attach to this episode, that Dr. Rahul Maheshwari, a nephrologist created. I think one other difference we should point out between lasix and bumetanide is that the bumetanide drip can give terrible myalgias and diffuse pains.

Dr. Andrew Ling: Yeah! I remember seeing this on my heart failure patients when they’re up to 2 or 3 an hour on the drip and they’re just feeling horrible. They’re pressing their call button. Asking their nurse, can you stop this?

Dr. Shreya Trivedi: Definitely something to watch out for! Okay, so with that, why don’t we transition to the oral loop diuretics. Especially since we have to think about what does we want to discharge people on once they leave the hospital.

Dr. Nicole Bhave: A common reason for admission would be, I’m taking my furosemide, but instead of kicking in within an hour as it should, it’s taking two or three hours and I’m just not urinating that much. And I went up on, up and up on the dose, and it still wasn’t working. Particularly with furosemide being less bioavailable than bumetanide and torsemide. That’s a common issue.

Dr. Shreya Trivedi: Okay, and as a quick review, when we say bioavailability, we mean how much of the medication actually gets in your circulation and is available to the system. So when we think about IV meds, its 100% bioavailable because it’s going directly into the blood and you don’t have to worry about wonky absorption or gut issues getting in the way.

Dr. Andrew Ling: Yeah and I was really surprised reading about that oral furosemide’s bioavailability is all over the place, anywhere between 10-90 or 100%, with 50% on average?!

Dr. Shreya Trivedi: Man! That is wild, Andrew! Yeah, I did know that the bioavailability was all over the place with furosemide, but I didn’t know it could be as bad as 10%.

Dr. Nicole Bhave: Particularly if someone’s come into the hospital and they’ve been on Lasix and it hasn’t been working for them, then most of the time, I will switch to torsemide or bumetanide.

Dr. Andrew Ling: So the good news is that oral torsemide and bumetanide have a bioavailability that’s usually above 80%. I think that would make anyone feel like these are more reliable!

Dr. Nayan Arora: I love torsemide, right? I love torsemide. Again, pharmacokinetics makes a lot of sense. It has a longer duration of action. It’s more predictable in terms of its bioavailability when it comes to obviously the oral dosing, and there was a study on this, it’s called the Transform-HF trial, and I thought this was going to be a cakewalk for torsemide. I thought this was like, I don’t, Super Bowl 42, I thought this was Giants versus Patriots. Torsemide is going to blow Furosemide out of the water, but that’s why you do the studies. That’s why you play the game. And the pharmacokinetics didn’t match up, and actually there was no difference in the two.

Dr. Shreya Trivedi: Okay! That sound byte might be a sore subject for some of our colleagues in Boston. But man, what a shocker, despite the pharmacokinetics, when we studied this in the real world, there was no difference in patients who were hospitalized for decompensated heart failure and were discharged either on oral torsemide vs. oral furosemide.

Dr. Nayan Arora: I have a lot of issues with that study. They were looking at mortality outcomes, which I just don’t think you’re going to see a mortality difference when you’re looking at two agents of the same class like that. I would’ve liked to see other outcomes. That being said, there’s nothing I can show you to say that one is better than the other except for the fact that I just like torsemide better.

Dr. Andrew Ling: Our reviewers also mentioned other issues with the study including a lot of crossover between the two groups. And I’m with Dr. Arora – it feels like mortality is probably not the right thing to look at. I wonder if maybe they would have been able to show a difference in heart failure exacerbations or rehospitalizations, maybe?

Dr. Shreya Trivedi: Yeah! I hope somebody is studying it! Hopefully there is a NIH grant cooking somewhere looking into all that.

Dr. Andrew Ling: I hope so because that would change a lot of things for a lot of patients. Just a few other things to mention about the oral diuretics. Torsemide has the longest duration of action as mentioned – anywhere from 6-16 hours so it can usually be dosed once a day. Bumetanide has the shortest duration with 4-6 hours. So multiple times a day dosing is usual for that.

Dr. Shreya Trivedi: Yeah and that’s especially good to keep in mind with bumetanide, right? Is our patient going to be compliant with multiple times a day dosing.

Dr. Andrew Ling: Right, I think its good to keep in mind for lasix too. It’s is in the middle of the two durations, but still on the shorter side in the 6-8 hour range.

Dr. Shreya Trivedi: Yeah and then last couple things to sway us towards torsemide. I didn’t know this before this episdoe, but it turns out torsemide’s absorption is less affected by food intake (unlike the other two diuretics). And then on top of that, torsemide has been shown to cause less hypokalemia than furosemide in some studies – and the thought is that because torsemide also has some aldosterone antagonist effects. Which is pretty cool!

Dr. Andrew Ling: Wow, I didn’t know either of those things! I was already on Team Torsemide, I love using it in my outpatients.

Dr. Shreya Trivedi: Yeah, nice! I love that! So while we are on the topic of oral diuretics, what dose should we discharge patients on? I feel like that’s always like a guessing game kind of.

Dr. Andrew Ling: For sure! And different people always pick different numbers. Do you just discharge the patient on the same oral dose they were on before or do you go up because maybe that home dose isn’t enough anymore?

Dr. Nicole Bhave: With that said, whenever you discharge someone from the hospital, close follow up is of course critically important because it’s very easy to overshoot. And we often find that after you kickstart someone with IV diuretics, their PO diuretic sensitivity will improve again. And it can often be a moving target as to what, what dose they need to be on.

Dr. Andrew Ling: I really appreciate hearing that and that PO diuretic sensitivity may actually improve! Which makes sense because hopefully you’ve gotten rid of the gut edema that was affecting your absorption.

Dr. Shreya Trivedi: Yeah that makes sense! I’ve certainly increased the oral lasix dose or torsemide dosing on discharge without really taking into account that PO diuretic sensitivity improving.

Dr. Andrew Ling: Well don’t beat yourself up about it, Shreya. I think everyone just picks a number. The most important thing is to see what happens after. I think this is a good reminder to think about what is bringing you patient in. Maybe if the patient’s coming in after missing some days of diuretics or because of dietary indiscretion, then sticking to their old dose might be okay. But if something else is going on, you might feel like you should increase their dose or even change diuretics entirely.

Dr. Shreya Trivedi: Yeah! And maybe the biggest takeaway, really, is to discharge them with a close follow-up and hopefully a VNA to check up on their weight, their kidney function, make sure their symptoms are in a good homeostasis with that discharge diuretic dose.

Dr. Andrew Ling: So, why don’t we summarize then. With IV diuresis – it’s dealer’s choice since there is no difference between IV furosemide and bumetanide, but bumetanide is much more potent mg per mg so it’s easier to reach for higher equivalent doses.

Dr. Shreya Trivedi: Yep! When it comes to oral dosing, furosemide has pretty big range of bioavailability of 10-100% and on average may be our patients getting around 50% of that furosemide dose. Compare that to torsemide and bumetanide where we can feel comfortable that over 80% of those diuretics will get into the circulation.

Dr. Andrew Ling: The duration of effects are also different with bumetanide and furosemide being shorter acting and torsemide being the longest acting. Usually this means oral bumetanide should be dosed twice a day while you can stick with once a day for oral torsemide.

Pearl 3 – Assessing Diuretic Response

Dr. Shreya Trivedi: Andrew, I guess the question is, how do we know if we are getting the diuretic response we want?

Dr. Nayan Arora: The classic metrics we use, which is going to be cumulative output and then weights, they unfortunately haven’t been shown to be super predictive of outcomes. I think part of the reason is that it’s hard to accurately measure those things in the hospital.

Dr. Shreya Trivedi: Oh yeah, all those times where the morning weight is up and down or the patient is charted net negative 1.5L but that’s hard to believe they only took in 200 cc, which I don’t know about that. With all that being said, I think my all around favorite clinical hack to move care forward is to use the urine sodium to know if I’m giving an effective diuretic dose.

Dr. Nayan Arora: The metric we use personally, and it is supported by data, is looking at a urine sodium, which is a spot sample one to two hours after you give them their diuretic. I personally use a threshold of 70, so urine sodium of 70. Studies have been anywhere from 50 to 100. Those studies have been, they hit the door, I give ’em a loop diuretic after they’ve emptied their bladder. I check a urine sample and it’s whatever threshold. Plus, it allows me to escalate therapy more quickly. If I do have an intervention, check your urine sodium two hours later, I can very quickly increase my meds, titrate, do whatever I need to do versus waiting, let’s say a day to see what their weight’s doing or whatever classic metric you’re using..

Dr. Andrew Ling: Yeah, one thing I also do which I do this is write in the Lasix order to have the patient empty their bladder before giving the dose and then order the urine sodium to be collected 1-2 hours later.

Dr. Shreya Trivedi: Oof, yeah I’ve def probably interpreted a urine sodium from first void after a lasix dose and it was probably just old urine that was already in the bladder and not reflective of the lasix dose. And it also just makes me think, Andrew, are there other things we should also be mindful of when we are interpreting a urine sodium?

Dr. Nayan Arora: So you have to be careful because urine sodium, again is influenced by the concentration or dilution of your urine. And so if I have somebody who’s only peeing one liter, I really don’t need a urine sodium because that patient is not responding well no matter what. And the urine sodium might be falsely reassuring just because the urine’s concentrated. Similarly, if I have somebody urinating 10 liters, I probably don’t need a urine sodium because it might be falsely lower just because it’s diluted.

Dr. Shreya Trivedi: That’s a great point I don’t think about as often. Concentrated urine can make that urine Na falsely high and give false reassurance that our diuretic dose is right, and dilute urine can make the urine sodium seem lower and we can be falsely disappointed.

Dr. Andrew Ling: Yeah! Maybe goes back to the larger hidden message in all of this which is the urine sodium is just one data point and needs to be taken into context of total output, weight, symptoms, and all. But at least it’s an objective data point that can give you some more confidence.

Dr. Shreya Trivedi: Yeah, I like reaching for the urine sodium especially when our patients are incontinent or for whatever reason, only about to get bed weights.

Dr. Nayan Arora: Other things that can influence your urine sodium in general is metabolic alkalosis. You have to deliver bicarbonate distally. So with that comes sodium, so you can influence your urine sodium with bicarbonaturia. The other thing is certain medications used in the hospital, one of the biggest ones is piperacillin. So if you have somebody on piperacillin-tazobactam, the piperacillin pulls sodium with it.

Dr. Shreya Trivedi: One way to think about it is Na is like this tag along friend comes along for the ride with the piperacillin and elevated bicarb in metabolic alkalosis.

Dr. Andrew Ling: That’s a fun way to think about it. Thinking about it more too, I imagine another confounder to be mindful for the urine sodium of is in cirrhosis, where patients have some extra volume in their abdomen and legs but can also still have a low urine sodium even when you’re giving them diuresis.

Dr. Shreya Trivedi: Yeah, that’s a good throwback to the hyponatremia episode where one of our nephrologists was like yeah, in patients with cirrhosis, their RAAS system is always going to be activated because of low systemic vascular resistance. And when the RAAS system’s up, your body retains as much sodium as it can and the urine sodium’s low.

Dr. Andrew Ling: Well, I guess it was always too good to be true for the urine sodium to be completely foolproof

Dr. Shreya Trivedi: Yeah, as much as I love it.

Dr. Andrew Ling: But it sounds like it can be really helpful when you can trust it! And just to put it out there, if you look at your data (including urine sodium) and feel your patient is not responding to the current dose of diuretics, the general advice is to double your loop diuretic dose as a next step.

Dr. Shreya Trivedi: Yeah and that brings me to something else I was hoping we could touch on, which is the creatinine. I think we’re all kind of nervous to see what the creatinine is going to come back as the next day. I wonder if there is a good way to think about the creatinine fluctuations we see in cardiorenal syndrome?

Dr. Andrew Ling: Yeah, I’d definitely like to talk about that too. I know often we say “diurese through a creatinine bump,” but I’m with you, I’m really not sure how much is too much!

Dr. Nayan Arora: There’s actually studies that show you’re not better off when your creatinine gets better. So the DOSE trials showed that if your creatinine got better, you had worse mortality than if your creatinine got worse during a hospitalization for decompensated heart failure and multiple trials like that showing that.

Dr. Shreya Trivedi: Oh wow, I can’t tell you how many times I’ve heard “oh the creatinine is getting better, that’s reassuring”. It sounds like that might not always be true.

Dr. Nayan Arora: A creatinine rise of 30% or less, I barely look at, so that I kind of give them and won’t kind of pause once it gets to that. And I personally am a little braver. So 30% is what’s shown in most of the studies. You saw this bimodal distribution of outcomes in the DOSE trial. If your creatinine got worse by 50% or more, you did significantly, you started to see this worsening in hard outcomes.

Dr. Andrew Ling: 30% and even maybe up to 50% bump? That sounds like way more than what I’m usually comfortable with for a creatinine rise!

Dr. Shreya Trivedi: Yeah! And just to clarify, we’re talking about a 30% or 50% creatinine bump from their baseline. So not the creatinine they came into the hospital with.

Dr. Nayan Arora: If you have a creatinine of three and it goes to four, it’s increased by 33% basically. It scares people, right?

Dr. Shreya Trivedi: Yeah, I’m glad to hear that, because I think when the Cr number is higher say in the 2 or 3s it’s harder to appreciate what a 30% rise in Cr really is.

Dr. Nayan Arora: And what I tell people is you see this in a lot of other places in medicine that you accept, and we need to do the same thing for active decongestion. When you guys give people RAS inhibitors, the classic board question is, how much of a rise do you tolerate? It’s 30%. SGLT2 inhibitors. Everyone’s favorite medication, same thing. You get a creatinine bump. 30% is kind of the quoted tolerated amount, but that leads to better long outcomes, blood pressure control.

Dr. Andrew Ling: Yeah in these situations with RAS inhibitors and SGLT2s, the thought is you’re putting less pressure on each glomerulus to be working overtime, so it looks like your kidney is “not working as well” when that’s not really true.

Dr. Shreya Trivedi: Right, with these medications, were helping each glomerulus work less hard is actually protecting them from getting too worn out in the long-term.

Dr. Andrew Ling: Yep, so I think the key point really is that a creatinine rise – like in those situations – does not always mean nephrons are “injured”. And in the case of decongestion, another reason the creatinine might “look worse” is because you’re hemoconcentrating the creatinine in your blood if you’re diuresing well.

Dr. Nayan Arora: It’s also really easy to point to studies that say, look, if your creatinine goes up by 30%, 50%, that’s okay. But when you have that patient in front of you with all these different things they’re telling you by history, their labs are all nuts and you don’t feel confident about your volume status, it’s very different than in a trial setting. In between, I’m still doing my due diligence every day. If I’m seeing this creatinine go up at some point, maybe I need to re-spin the urine. Maybe they have another process going on. All the different things we mentioned previously for acute kidney injury can still happen, but as long as I’m not seeing any other issues, I keep going.

Dr. Shreya Trivedi: Again that’s good spaced repetition to Pearl 1. We should be constantly reassessing for other kidney insults, especially in the hospital.

Dr. Andrew Ling: Yeah! And now I’m going to be thinking about it all the time, everyday. Looking at my patients labs.

Dr. Shreya Trivedi: You’re going to be a great nephrologist, Andrew.

Dr. Andrew Ling: Let’s summarize about assessing diuretic response. Outside of our traditional weights and Is/Os, an elevated spot urine sodium taken 1-2 hours after giving diuretic is a good marker of diuretic response. Some of our experts use a urine sodium threshold of 70 mEq/L but different studies have any number between 50-100 mEq/L as the cutoff. And you should have the patient empty their bladder before giving the diuretic and then collect this sample, in an ideal world.

Dr. Shreya Trivedi: Okay, as much as I love the urine sodium, it is not foolproof! Especially, if someone is urinating a lot or very little, that urine sodium may not be as accurate. And you probably in those situations already know how the person is responding! It’s may be more helpful in more of those gray areas when combined with urine volume. And other things to look out for in interpreting it is metabolic alkalosis. Are they on certain medications (like pip-tazo) that can make the urine sodium high and falsely reassure you that your diuretic dose is effective.

Dr. Andrew Ling: And the other thing we talked about was creatinine rises during diuresis. Patients with decompensated heart failure whose creatinine initially rose up to 30% from their baseline with diuresis actually did better than those whose creatinine went down right away with diuresis. This rise is usually not because of actual kidney tubular injury.

Pearl 4 – How to approach diuretic resistance

Dr. Andrew Ling: Alright, so we follow the urine output and urine sodium for Ms. CR and unfortunately aren’t having much response. Her Lasix gets doubled, tripled, and eventually she’s on a drip and she’s urinating maybe 1L per day with a urine sodium still low in the 40-50 range. What do we do now?

Dr. Shreya Trivedi: Yeah, so let’s talk about this! Diuretic resistance – what’s our approach here?

Dr. Nayan Arora: The first step is does my patient have flow? If you don’t have appropriate renal perfusion, it doesn’t matter what you do with your diuretics.

Dr. Shreya Trivedi: Ugh! Okay, another reminder about that diagnostic timeout: if you’re just cranking up the diuretics and not making any headway. Could there be something else affecting kidney perfusion like cardiac output or ascites?

Dr. Andrew Ling: Right, Dr. Arora told us about one case where a patient had ascites causing an abdominal compartment syndrome so they continued to have “diuretic resistance” and poor urine output to increasing and increasing doses of Lasix.

Dr. Shreya Trivedi: And we’ll get to hear that crazy case and some more diuretic resistance cases next week! On next week’s episode.

Dr. Andrew Ling: Sounds good, I’ll be looking out for it! Let’s say we are confident we don’t have things like low cardiac output or ascites impacting flow to the kidneys. I feel like at this point I’ve heard different people reach for metolazone or chlorothiazide or other diuretic boosters but I don’t really have a great framework for how to think about that.

Dr. Nicole Bhave: Often times in outpatient setting with heart failure patients who are diuretic resistant, we’ll use metolazone, which has a really long half-life.

Dr. Nayan Arora: It is kind of like your glargine of diuretics. It’s your long-acting. It’s nice in that way. Versus chlorothiazide does work quicker, right? IV Chlorothiazide has a rapid onset of action, but it only lasts about two hours or so. And so there are reasons why metolazone may be actually favorable.

Dr. Shreya Trivedi: Okay and then clinically, there’s no real difference between the effect of metolazone or chlorothiazide. I think really the difference to know is that IV chlorothiazide is faster onset and another practical point, more expensive.

Dr. Andrew Ling: I hear you, Shreya. I feel like despite the data, I’ve seen a lot of attendings who stylistically prefer chlorothiazide. I think because it feels like it works faster and since it’s IV, you’re not messing with oral absorption.

Dr. Shreya Trivedi: Yeah! I get that, I get that. And you know there’s another booster that I hear people talking about or tweeting about, every now and then, or x-ing about. Acetazolamide! I guess that’s something good we can reach for, especially if that bicarb is starting to go up and they’re still volume-overloaded.

Dr. Nicole Bhave: There was a paper in the New England Journal a year or two ago that suggested that it has, you know, benefit in acute heart failure. It’s nice for people who have who are alkalotic.

Dr. Shreya Trivedi: Right, and it looks like the trial Dr. Bhave mentioned was the ADVOR trial. It was randomizing patients to loop diuretic plus acetazolamide or loop diuretic alone.

Dr. Nayan Arora: The acetazolamide arm did have increased fraction excretion of sodium. They had decreased length of stay and more patients were decongested, I believe at the 48 hour mark compared to the control group. So I love acetazolamide. I will tell you I absolutely love acetazolamide. We started using it several years ago and I think it works really well.

Dr. Andrew Ling: Sounds like acetazolamide’s really got a lot of fans! I’ll be sure to think about acetazolamide earlier next time, especially if the patient’s bicarb is up to the high 30s or near 40 (like COPD patients) and are still volume overloaded.

Dr. Shreya Trivedi: Yeah, I definitely haven’t used it much and hopefully will remember to reach for it more in these sticky situations.

Dr. Andrew Ling: Of the diuretic boosters we talked about, at least in this episode, we have metolazone, chlorothiazide, acetazolamide. What types of things should we be watching out for when we use these?

Dr. Nicole Bhave: Some people are just so sensitive to it (metolazone) that you just, volume deplete them rapidly and they develop AKI you also have to worry about electrolytes.

Dr. Nayan Arora: You want their potassium certainly greater than four. There’s actually data to show that hypokalemia is an independent risk factor for diuretic resistance. And so electrolyte monitoring and repleting these appropriately adding potassium sparing diuretics early, whatever you want to do to maintain electrolyte balance is important.

Dr. Shreya Trivedi: We’ve definitely talked about keeping that K above 4 when we’re worried about arrhythmias and things like that (we did a whole hypokalemia episode on it) but I never thought about hypokalemia actually making you respond worse to diuretics.

Dr. Nayan Arora: So particularly when we start talking about things like acetazolamide and your other diuretics, you can waste magnesium. And so that’s something you generally want to replace because your potassium’s not going to get better until you replete magnesium.

Dr. Shreya Trivedi: So it sounds like mainly be careful about those pesky electrolytes. Maybe reach for RAAS inhibitors or spironolactone as our friends here. And of course, watch the volume status especially when turning on the boosters.

Dr. Andrew Ling: After all that, let’s say you try everything and your patient is still not urinating much? And your attending is like, “find renal, this patient needs dialysis.”

Dr. Shreya Trivedi: Haha! I hope I never say “find renal!” That reminds me of those Dr. Glaucomflecken skits like with the cardiologist and nephrologist showdowns.

Dr. Andrew Ling: Yeah, I love those. And I’m just thinking of the nephrologist holding the salt bag.

Dr. Shreya Trivedi: Yeah! I’m thinking about that too.

Dr. Andrew Ling: Hopefully, the real world has more peaceful interactions!

Dr. Shreya Trivedi: Exactly! So how do we think about dialysis or ultrafiltration in the grand scheme of this? You know, I do often see as the last line when patient’s are not responding but I don’t know if there is role for it earlier?

Dr. Nayan Arora: The hesitation is it’s not a benign thing to put somebody on dialysis. You have hemodynamic issues with dialysis. It’s less common, but you can have issues with catheter placement and complications that come with that. And then again, if we borrow from other literature, it’s more likely that they’re dependent on dialysis at six months and dialysis sucks for patients. In my opinion, if I have tools to get their own kidneys to get rid of this excess fluid, I want to maximize those options before I go to dialysis. That doesn’t mean we don’t have those patients where we’ve tried everything.

Dr. Shreya Trivedi: I think that’s a great reminder about what we sometimes put our patients through.

Dr. Andrew Ling: It’s also a great reminder that dialysis is not a benign treatment and doing everything possible before turning to dialysis fits with what I’ve generally seen.

Dr. Shreya Trivedi: Yeah! So let’s put it all together with our framework for how we manage diuretic resistance. First and foremost, we should ask ourselves, if there enough kidney perfusion? Because diuretics won’t work if they’re not reaching the kidney! Right?Some more common things to think about are low-flow states like cardiogenic shock and increased intra-abdominal pressure from ascites.

Dr. Andrew Ling: Alright! Once you’re confident kidney perfusion is not an issue, there are three more common boosters you can reach for. The thiazides are usually our first line and include metolazone or chlorothiazide. Metolazone is much longer acting and cheaper. No difference in effectiveness has really been shown in studies, but chlorothiazide is IV so some prefer it for faster action and to not risk any absorption issues.

Dr. Shreya Trivedi: And with that, acetazolamide has made its re-appearance on the scene and is a great agent to think about adding on early as well, especially if alkalosis or COPD is an issue. But remember, with all of these “boosters” you have to be really careful to watch your electrolytes, especially potassium as low levels may actually encourage more diuretic resistance.

Dr. Andrew Ling: And finally let’s talk about ultrafiltration. In practice, it’s usually used once all other options have been exhausted because of the existing studies and dialysis initiation has its own risks. That said, some people are still exploring the role of earlier UF. But there is not much that has been widely established about that.

Pearl 5 – Don’t be afraid of medical therapy because of CKD

Dr. Andrew Ling: Alright, so for Ms. CR, we’re finally able to add some metolazone and acetazolamide and thankfully she;s starting to feel better without needing dialysis. Her creatinine was starting to downtrend by discharge in the low-mid 2s, not quite back at her baseline when she’s leaving the hospital.

Dr. Shreya Trivedi: And then from here we have to really think about her CKD management! And that brings us back to a throwback to the GDMT Part 2 episode on heart failure meds in CKD.

Dr. Nayan Arora: So we completely under utilize these out of fear of people’s underlying kidney function. We need to recognize that these are the best medications we have to actually keep people off dialysis.

Dr. Shreya Trivedi: So as a refresher and throwback to our GDMT episode, in the CKD III range, you should absolutely try to get the RAAS inhibitors and SGLT2 inhibitors on board. It;s good for both heart and proteinuric kidney disease. But it can be trickier especially when that eGFR starts creeping into the CKD IV range.

Dr. Nayan Arora: And so right now, what we have is that to initiate an SGLT two inhibitor, the studies show that as long as your eGFR is above 20, that you should go ahead or it’s appropriate to initiate. The issue with that is that that doesn’t mean that starting at lower eGFRs is wrong, it just means it hasn’t been studied yet.

Dr. Shreya Trivedi: For me, the biggest teaching from that episode is that it’s probably safe to continue the SGLT2 inhibitor even if the GFR drops below 20, as long as it’s not giving the patient any issues.

Dr. Andrew Ling: Right! And it’s a similar story as CKD progresses to not stop RAS inhibitors.

Dr. Nayan Arora: We have data to show that there’s no reason to discontinue RAS inhibitors if somebody’s already on it, regardless of what their eGFR is. So even if it falls into that CKD IV, CKD V range, that was the STOP-ACE study, which showed that strategy didn’t impact hastening of dialysis. Whether it’s helpful, it’s not clear. We are left with a lot of propensity match studies, observational studies, other studies that show that there probably is cardiovascular benefit to continuing those RAS inhibitors. Unfortunately, the STOP-ACE study wasn’t empowered to look at that variable. My strategy is unless I’m dealing with potassium issues to keep them on those agents.

Dr. Shreya Trivedi: And as a throwback to another CoreIM episode we had on hyperkalemia! We can also think about using potassium binders to help balance out the potassium to try to keep the RAS inhibitor on. My go to K binder is Lokelma, sodium zirconium cyclosilicate. It’s easy to take and tasteless.

Dr. Andrew Ling: And one of my favorite things to do is to start the SGLT2 inhibitors with the RAS inhibitors and MRAs since SGLT2s can be protective against serious hyperkalemia.

Dr. Shreya Trivedi: Ah, yeah, good pro tip. And speaking of the mineralocorticoid receptor antagonists, the MRAs, I do hear about finerenone making an appearance on the scene. And I believe is more selective MRA than the non-steroidal MRA, that we know, spironolactone, and has been shown to cause less hyperkalemia. Andrew, what do you know about it?

Dr. Andrew Ling: Yeah, I’ve heard the same thing, Shreya. That potassium issue definitely makes it more appealing. Finerenone’s been shown to slow CKD progression in proteinuric diabetic kidney disease. Especially here, I’ve seen some of the nephrologists especially at our diabetes center start using finerenone as a third line if there’s still a lot of protein in the urine even after maxing out your RAS and your SGLT2.

Dr. Shreya Trivedi: Yeah! So sounds like there are more studies to come for whether finerenone has a proven role as a GDMT in heart failure. So more things to look out for!

Dr. Andrew Ling: Yes, I think it would be exciting if finerenone becomes established for heart failure on its own. Just to throw it out there, I think next things in the pipeline may be the GLP1s. Our favorite for obesity and diabetes, which may have some benefit for heart and kidney disease even outside of diabetes.

Dr. Shreya Trivedi: So many good developments in the world of CKD and heart failure, and I’m glad our patients are getting that attention and research!

Dr. Andrew Ling: So to recap all of this, with most of these heart failure GDMT meds we can and should continue RAS inhibitors, SGLT2s, and MRAs as CKD progresses since their protect both organs. The main thing to look out for is potassium issues, not the creatinine. There are some different eGFR cutoffs for initiation of these medications, but these are rapidly evolving. It’s generally safe to continue at least RAS inhibitors and SGLT2s if they’ve already been started even if the creatinine continues to get worse.

Dr. Shreya Trivedi: And on that note, that’s a wrap for today’s episode! Please share this with a colleagues or anyone who may find this helpful.

Dr. Andrew Ling: And thank you to our reviewers Dr. Nisha Bansal and Dr. Sunu Thomas from the University of Washington. This episode was made in part from the Digital Education track at BIDMC. So would like to thank Shreya, our other host here, as well as, Dr. Adam Rodman and my co-residents who are on the track. Thank you to all the mentors involved in the work!

Dr. Shreya Trivedi: Awesome, Andrew. Thank you to Daksh Bhatia for the audio editing and to Dr. Rahul Maheshwari for the infographic. Opinions expressed are our own and do not represent the opinions of any affiliated institutions.

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