Time Stamps

CME-MOC

Show Notes

1. Referral for urgent management of hyperkalemia

  • Current guidelines from kidney international suggest that the following outpatients should be referred for urgent management:
    • K+ > 6.0 mEq/L with OR without ECG changes
    • Anyone with hyperkalemia and documented EKG changes 
  • However, there is no consensus on these recommendations and many clinicians manage hyperkalemia in the outpatient setting differently (especially with hyperkalemia < 6.0 mEq/L)

2. Hyperkalemia and ECG changes

  • A retrospective chart review of 90 patients admitted with severe hyperkalemia (K+ > 6 mEq/L) showed only 52% met criteria of having any ECG changes. 
    • The study authors concluded that the ECG was insensitive for diagnosing hyperkalemia
  • Recent retrospective study from 2019 compared ECG findings of 3 groups and found no significant difference in the frequency of ECG changes between the normokalemia (K+ < 5.1 mEq/L) and moderate hyperkalemia (K+ between 6 and 7 mEq/L) groups.
    • For every patient including those in the severe hyperkalemia group (K+ > 7.0 mEq/L) more than half did NOT have any ECG changes.  
    • Take-home point: ECGs are not sensitive in the detection of hyperkalemia.  The absence OR presence of EKG changes does not predict the presence of hyperkalemia.
  • A Case report from Japan discusses a patient with an initial potassium of 8.5 mEq/L and a normal ECG. It was not until after the patient’s potassium was corrected and then their hyperkalemia acutely recurred that they developed a sine wave pattern on ECG.
    • There is no consensus or solid data on what “chronic” hyperkalemia means, with respect to how high or how long a patient needs to have it.
    • Take-home point: The abrupt change from normokalemia to severe hyperkalemia, not necessarily the K+ level itself, is most worrisome and needs to be treated.

3. Pseudo-hyperkalemia

  • Conditions that lead to pseudo-hyperkalemia, the in vitro release of intracellular K+
    • Excessive tourniquet use
    • Fist clenching
    • Vein trauma from multiple phlebotomy attempts 
    • PICC/central line draws
    • Use of serum separator tube (clot activators) – commonly used to measure the “basic metabolic panel” 
  • Sending a whole blood sample, sent to the lab in an anticoagulated tube, is the most reliable way to get an accurate potassium reading

4. K+ restricted diets

  • Lots of foods high in potassium are part of a healthy diet such as fruits like; oranges, mangoes, avocadoes, melon, prunes, raisins, and dates.
  • Avoid generalization like, “restrict all plant based foods”.
    • Some studies suggest that potassium from plant foods (perhaps due to their cell walls) have limited bioavailability and therefore, are poorly absorbed.
  • Plant based foods, although potassium rich, have high amounts of fiber and alkali, which can counteract the metabolic acidosis of CKD. 
  • High potassium diets have been linked to better blood pressure control and improved cardiovascular mortality in patients with hypertension. 
  • Low potassium diets have been shown to increase sodium reabsorption, and worsen blood pressure control, and can even lead to progression of CKD.   
  • Pro-tips to avoid Nutritional Confusion:
    • Individualize dietary counseling, take a detailed dietary history. 
    • Salt substitutes are often Potassium Chloride (KCl), and should be avoided. 
    • Juices and sauces can be high in potassium and do not have significant dietary benefits. 
    • Constipation and fasting can lead to elevated potassium levels. 
    • For potato lovers, leaching your potatoes is a great way to reduce their potassium levels.
  • Take-home point: Complete elimination of K+ from the diet is not advisable.  High K+ foods should be consumed in moderation, as they provide significant cardiovascular health benefits, especially for those with CKD.

5. Key medications that can cause hyperkalemia

  • Renin-Angiotensin-Aldosterone System Inhibitors 
    • RAAS inhibitors improve mortality, but are often the first medications to be discontinued when hyperkalemia is detected.
    • It is difficult to predict how much the potassium will improve with stopping a RAAS inhibitor. 
    • Consider the factors that determine each individual patient’s potassium balance, for example diabetics have lower levels of insulin (or higher resistance) meaning less insulin surge post meal and less intracellular potassium shift. 
    • Also some patients with diabetes are in a hyporenin hypoaldosteronism state, making the kidney much less efficient at excreting potassium. Use of a RAAS inhibitor in these patients is a recipe for hyperkalemia.
  • NSAIDS
    • NSAIDs (and beta blockers) decrease renin release (and less RAAS activation), which decreases potassium excretion leading to hyperkalemia. 
  • Trimethoprim Sulfamethoxazole 
    • Antibiotics like TMP-SMX block potassium excretion in the collecting duct of the nephron leading to hyperkalemia. 

6. Treating outpatient hyperkalemia

  • Sodium polystyrene sulfonate (SPS, a.k.a Kayexalate)
    • Most of the data on SPS is retrospective, without any RCTs.
    • Retrospective cohort study of 1.8 million patients over age 66 showed SPS users had 2x higher rates vs. controls of having GI events like: intestinal ischemia, thrombosis, ulceration, perforation, resection, or ostomy creation.
    • Most patients find SPS difficult to drink, as it tastes disgusting inhibiting long term use. 
  • Patiromer
    • Gemstone trials – AMETHYST, OPAL-HK, and AMBER
      • Patiromer is effective at lowering K to more manageable levels 
      • High proportions of patients were able to stay on their RAASi 
      • Main side effects were hypomagnesemia and constipation, both reversible and manageable
  • Sodium zirconium cyclosilicate, SZC
    • Influential trials include HARMONIZE and ENERGIZE. 
    • The NEJM study in 2015 showed that 1 dose of SZC has a rapid onset, with normokalemia achieved in an average time of 2.2 hours
    • Main side effect = occasional edema (from the sodium load), without any increase in blood pressure
    • Patient tolerability is much better – easy to take and tasteless

Transcript

Jeff: Picture this scenario.  You get called or paged by the lab at 9pm with a critical lab result of an elevated potassium level.  

Larissa: Darn, those late night outpatient lab calls… 

Jeff: Yeah, so what do you do with that K in the outpatient setting?

Larissa: Usually, when I get those pages for hyperkalemia, my first instinct is to flip through the chart to see if this has ever happened before, kind of hoping I  can just do whatever the last person did to make the potassium better. 

Jeff: Yeah, but either way, if you’re calling a patient late at night about their potassium (assuming they even answer the phone), you better know what you’re gonna do about it.

Larissa: Right, that is so true!!! I can definitely remember one specific time when I got a  page about a K of 6.2 for a brand new patient with chronic kidney disease. When I called, she was actually at Faneuil Hall (a food market here in Boston). She was getting ready to have some baked potatoes with her family. It took a loooot of convincing to get her to the emergency room…and to put that potato down!

Jeff: Exactly! So let’s explore the very practical questions around hyperkalemia. 

Welcome to Mind the Gap, I’m  Jeff William, a nephrologist at the Beth Israel Deaconess Medical Center and assistant professor of medicine at Harvard Medical School.

Larissa: And I am Larissa Kruger-Gomes. Currently a  nephrologist at a private practice in RI and former fellow at BIDMC.

Jeff: So What’s on deck for today?  First, we’ll ask who needs to come into the Emergency Department for hyperkalemia? Or, simply put, how high is “too high”?

Larissa: Then we’ll get into if we should really be recommending a low potassium diet in patients with hyperkalemia?

Jeff: And finally – What are the potassium-reducing strategies we can use for our outpatients?

Larissa: Ok so say its 9pm and this K came back at 6.2. Do you call the patient tonight and recommend that they come to the ED? Or do you feel OK with them going to sleep blissfully unaware of their elevated potassium level.  Again, how high is “too high”?!

Jeff: I think we all have our own comfort levels about K.

Larissa: For sure – and probably different comfort levels depending on how many high K levels you’ve managed before. But, what do the guidelines say?

Jeff: The KDIGO guidelines acknowledge that the evidence is thin and the issues are not well studied. So the guidelines suggest we should urgently refer any outpatient that falls in one of two buckets.  The first bucket is to refer urgently for K >6.0, with or without EKG changes.  What do you think about this, Larissa?

Larissa: That’s straightforward enough! K greater than 6  equals ED for you.

Jeff: Yeah, for me too.  So the second bucket includes those with ANY degree of hyperkalemia and documented EKG changes. How about this one, Larissa? 

Larissa: This one’s a little confusing to me — let’s say  I have someone with a newly elevated K at 5.8. Am I okay to schedule a close follow up or should I send them to the ED?

Jeff: Ah yes. That is THE question!  If the patient is at home, we obviously can’t check an EKG!  The guidelines aren’t really helpful at all here with new hyperkalemia <6.

Larissa: So we’re kinda left to our clinical judgment?

Jeff: My interpretation of the guidelines is that I should get an EKG for any patient with new-onset hyperkalemia.  But... I can also tell you that lots of nephrologists and internists would probably disagree with what to do with a K less than 6.

Larissa: Jeff, We keep bringing up the EKG, so I have to mention another frustration of mine – hear me out. The main reason why we send patients to the ED is because we are worried not about the potassium, per se, but because hyperkalemia can lead to cardiac instability, right?

Jeff: Right…

Larissa: Alright, so what about  the patients you send to the ED with a K of >6 but when they get to the hospital they have absolutely no EKG changes? Did we just do a bunch of work for nothing?

Jeff: I hear you, but let’s take a couple of steps back here. The way I think about EKGs in this setting is kinda like a biopsy – you can have sampling errors! Just because you’re not seeing EKG changes right now it does not mean something would not have been present before or might be there in the very near future. 

Larissa: Ok, so Is there a potassium level cutoff that can help us predict EKG changes?

Jeff:  There was a retrospective study comparing the EKG findings of 3 different cohorts – mild hyperkalemia with K less than 5.9 mEq/L, severe hyperkalemia with K > 7.0 mEq/L, and a moderate hyperkalemia group with a K between 6 and 7.  

Larissa: So were there any differences between the 3 potassium groups?

Jeff: They found no significant difference in the frequency of EKG changes between the mild and moderate hyperkalemia groups. As a refresher that includes all patients with K < 7. 

Larissa: Whoa. Is there anything else that surprised you about the study?

Jeff:  So even when they looked at every patient in the study, including the severely hyperkalemic ones with a K > 7, more than half did NOT have any EKG changes! 

Larissa: That’s pretty much a coin toss.  

Jeff: So basically, the study authors couldn’t really pinpoint a threshold at which you would see an EKG change. But… they did note that the higher the K, the more likely it was that you’d see an EKG change. So, the takeaway here is something we’ve all experienced – the absence of EKG changes in a patient with hyperkalemia is actually really common!   

Larissa: I see, that is so weird. I was expecting more of an association between K and EKG changes. 

Jeff: Me too! And to drive this point home, check out this case report from Japan.  This 77 year old man with acute-on-chronic kidney injury comes in with a K of 8.5 mEq/L.  And his EKG was normal!  They treated him, adjusted the meds, and sent him home with a normal potassium. But then, he comes back 6 days later, and his K is back up to 8.6 mEq/L.  But this time, his EKG shows the scary-looking sine wave pattern.  

Larissa: Wow. That is a really interesting case! What I take away from this is that the absolute potassium  level alone doesn’t matter as much as how quickly you got there!

Jeff: Exactly. That change from normokalemia to a level of 8.6 was where this patient ran into trouble. For me, any abrupt change from normal to hyperkalemia is worrisome and needs to be treated.

Larissa: OK, so all of these points definitely make sense for those with new, acute hyperkalemia.  But what about those patients who ALWAYS have an elevated K+ when you check it as an outpatient??  The so-called “chronic hyperkalemia”.  What should we do for them?

Jeff: Well, the guidelines acknowledge that the higher the K, the higher the risk of cardiac instability.  But these guidelines don’t address what “chronic” really means.  There’s no consensus on how high or how long the potassium needs to be abnormal to be called chronic.

Larissa: Hmm, that is a lot of grey area! 

Jeff: Yep. That’s why it’s a Mind the Gap episode!

Larissa: I guess, for me… in these chronic hyperK cases I still apply the same principle we discussed for acute hyperkalemia  – I look at the delta between the last potassium and the one I have now. For example,  if someone has been 5.6 for a while and now they are 5.8…that’s not a lot of change. But if someone has been 5.6 and is now 6.2, I will think about it differently. 

Jeff: Okay, so let’s recap what we discussed so far. If somebody’s potassium is greater than 6, especially if it’s an abrupt change, they should have a STAT re-check, an EKG, and prompt treatment.  But what about hyperkalemia less than 6.0?  Well, it just hasn’t been well studied, but should be taken seriously if a patient’s potassium has quickly jumped from a normal level.

Larissa:  … and the higher the K, the more likely you are to see the classic EKG changes of hyperkalemia.  But there isn’t really a potassium cutoff where you know for sure you’ll run into trouble with instability of cardiac myocytes.

Jeff: OK, so based on the guidelines, Larissa… you have sent your baked potato-loving patient with CKD and a potassium of 6.2 mEq/L to the emergency department. The EKG is checked, but doesn’t show any changes. The repeat potassium is 5.4 mEq/L, without intervention.  

Larissa: Ugh how frustrating that happens all the time.

Jeff: Yep. So she’s sent home with close outpatient follow-up.  

Larissa: Jeff, that’s a big improvement  without any intervention.  Was it magic?!  

Jeff: Hmm, probably not.  It sounds like a case of “pseudo-hyperkalemia” to me. When the lab measures and reports hyperkalemia, but the patient’s actual circulating potassium is normal.   

Larissa: But wait, wait wait! the lab did not say the sample was hemolyzed! 

Jeff: Well, just because the lab didn’t report the sample as hemolyzed, it doesn’t mean there wasn’t extra K released.  Our cells are full of potassium, right?  And if they get damaged at all during the phlebotomy process, extra potassium is released within the blood collection tube.  Even if this is below the level that the lab considers the sample to be hemolyzed

Larissa: Yeahh… whenever a patient tells me that they’re a “tough stick”, I wonder if I’ll get called about their potassium later.  There are just so many opportunities for pseudo-hyperkalemia during a difficult blood draw.  There’s fist clenching, taking the tourniquet on and off, and vein trauma from multiple phlebotomy attempts.

Jeff:  Right. And the lab routinely measures electrolytes using a serum separator tube.  When a clot forms in this tube, more potassium is actually released from the red blood cells into the serum inside that tube.

Larissa: True. That is why your best bet in those cases is to send a whole blood sample to measure your K! This way the lab will use a tube with an anticoagulant and no clot formation happens – so no potassium sneaking out.

Jeff: Getting the whole blood K is my “go-to” also.  OK…so your patient with CKD now has a K of 5.4 when she comes back to the clinic.  Are you gonna counsel her on a low potassium diet now?  

Larissa: Actually…no!  I would start by asking her to share her diet with me.  Usually I start with a 24-hr recall of what she ate recently

Jeff:  You know what?  I definitely do this, but it doesn’t always reveal one of those classic high potassium foods, like bananas.      

Larissa: True. And bananas get a bad rap for being a high potassium food. But don’t forget some other common fruits, like oranges, mangoes, avocados, melon, prunes, raisins, dates – all of those have potassium too.

Jeff: Right. So many of these potassium-rich fruits and veggies are actually an important part of a healthy diet. This is where I struggle when counseling patients. I definitely don’t want my patients to be hyperkalemic, but I feel really badly about telling them to stop eating a healthy diet! 

Let’s hear more from Dr. Shivam Joshi. He’s a nephrologist at NYU whose research focuses on in nutrition and kidney disease.

Dr. Joshi: It’s not worth going through all this to explain to them and creating all this nutritional confusion. I think this should be used strategically and not universally. 

Jeff: Nutritional confusion – I can certainly see that happening… telling patients to restrict all these foods or measure how much K is in this or in that.

Dr. Joshi: For the most part, I try to steer away from the traditional logic of just restricting all plant foods. That all plant foods have potassium, all plant foods will raise your potassium level. Thus, we should restrict plant foods in patients with kidney disease. I think that doesn’t make sense. It’s not evidence-based.

Jeff: Not evidence-based indeed!

Dr. Joshi: We’re starting to get research suggesting that maybe potassium functions in the same way as phosphorus. And there’s a bioavailability aspect that not all the phosphorus or potassium going in is reflexively absorbed. People are saying that plant foods have cell walls and that because of those cell walls, potassium is contained in it, which makes it harder to digest and then ultimately be absorbed.

Jeff: OK, I see. So just because a food has a lot of potassium doesn’t mean we actually absorb all of it.  

Larissa: Yup. Actually a high potassium diet has been linked to things we love seeing in patients  like better blood pressure,  improved cardiovascular mortality and ( the dream!) decreased rates of CKD 

Jeff: To me, as a nephrologist, what I find so interesting is the mechanism behind high potassium intake and blood pressure control.  When you eat lots of potassium, there are K sensors on the renal tubular epithelial cells that will inactivate the thiazide-sensitive channel. So basically, a high potassium diet is like taking a thiazide diuretic.  You’ll pee out more volume and the blood pressure gets better!  

Larissa: So is the opposite also true – low potassium in the diet leads to worse blood pressure?

Jeff: Definitely. A low potassium diet results in increased Na+ reabsorption, and worsening blood pressure control.  In fact, a low potassium diet has been associated with progression of chronic kidney disease – the exact opposite of what we’re trying to accomplish for our patients.

Larissa: Those are great pathophys nuggets to keep in mind! My other nugget for why I am not a fan of counseling patients on low K diets is that fruits and veggies actually provide a lot of alkali!

Jeff: As Meghan Trainor once said, “you know I’m all about that BASE”.  

Larissa: She DID say that! But I’m not sure we’re talking about the same base…

Jeff: OK, maybe not, but increased alkali with fruits and veggies definitely counteracts the metabolic acidosis of CKD.  Remember we don’t like metabolic acidosis! It actually worsens hyperkalemia.

Larissa: We will link to an article in the show notes about the the pathophys and K-H channels if you want to read more.

Jeff: Yep and metabolic acidosis is also associated with worsening CKD…and higher mortality!  So I have learned NOT to underestimate a low bicarb in a patient with hyperkalemia.

Dr. Joshi: I think that gets missed a lot into the other thing is, uh, is metabolic acidosis. I can tell you the number of times I’ve been referred hyperkalemia management and renal clinic, and either by their, their average bicarb is 10 or 14, you know, we’re not correcting the bicarb.

Larissa: Yeah that is really low – but I am even giving bicarb when its 18s-20s! Alright – I hope we sold people on not going too too crazy on the low  potassium diet.  Jeff, is there anything else as far as diet that we didn’t mention and you ask your patients about?

Jeff: Yeeah I also double-check that they haven’t replaced their salt intake with a salt substitute!  Those salts are usually potassium chloride  – exactly the electrolyte we’re trying to avoid here. And I also ask about sauces,  juices, and smoothies. These are big problems too!  Think about all those fruits you need to make juice or a smoothie.  Way more than what you would actually eat! Dr. Joshi still remembers a case where juice was a player in a sudden K bump.

Dr. Joshi: I remember rounding on her and her potassium had suddenly increased. And, uh, as I entered her room, uh, there was all these juice containers here, you know one cup size that the foil on top and you peel it back and she had all of this, she loves cranberry juice and all of these containers were just thrown in the trash can. And I think it’s because she didn’t like water or there wasn’t anything else for her to drink. So the entire day before and evening before she was just drinking all this cranberry juice, that will always stick with me. 

Larissa: [that’s a good story] Here is another ding against juices vs the whole fruit —  often people are using some juicers and blenders that just take out all that healthy fiber – everyone knows that a low fiber   diet  can cause constipation and  fun fact, that can affect the potassium as well!

Dr. Joshi: There is some research to suggest that with declining kidney function, that you can get an increase in colonic secretion of potassium. This is not established or some studies that don’t show this, but if it does happen, you cannot get the benefit of it if you’re not having a bowel movement. So one of the questions I asked are they constipated. Some people think that the benefit of Kayexalate is actually just because it induce a bowel movement and it was a laxative.

Larissa: In addition to making sure we’ve got good flow with whats going out by taking care of constipation, we gotta make sure enough is going in.

Dr. Joshi: I will say that fasting can also raise potassium levels because of the lack of insulin  being used with eating. So sometimes if someone’s fast, you may get a little bit of hyperkalemia with that. 

Larissa: Yeah, you can definitely notice that on AM labs in the hospital sometimes – which is yet another reason why sometimes just repeating a potassium level helps. Hey Jeff, Do you have any other good dietary tips for limiting potassium intake, but still eating a healthy diet?

Jeff: Sure. For your potato-loving patient, you can ask her to leach them. Leaching means cutting the potatoes into smaller pieces, soaking them in water, boiling them, and draining them to get out that potassium.  The leaching process will get rid of about half of the potassium content!  Hey Larissa, time for a recap?

Larissa: Yes. No one size fits all here –  Individualized counseling is the way to go – look for those culprits of high potassium foods that don’t give you dietary benefits – like juices and smoothies! Ask about constipation and fasting. 

Jeff: Alright, so what about the meds?

Larissa: So we have to talk about RAAS inhibitors here. Yes, they  can all lead to hyperkalemia…and, yes, we often instinctively stop them in the face of acute hyperkalemia.  This is probably a good thing … just like when we stop them for AKI. But when should we restart them?

Jeff: I see so many patients in clinic with CKD and diabetes who’ve been taken off their RAAS inhibitor during a recent hospital stay. The discharge summary says, “Follow-up with your doctor about restarting your lisinopril.” 

Larissa: Yup.  I’ve definitely written that in my discharge summaries as a resident!  I think we’re all trying to do the right thing here. We all know that RAAS inhibitors improve mortality and slow the progression of chronic kidney disease!  

Jeff: Absolutely. I can’t stress this enough.  This question is settled. RAAS inhibitors save lives.  But for patients with hyperkalemia, so many are on diuretics but not RAAS inhibitors. That’s just not a fair trade.  It would be like trading Pat Mahomes away for….Tom Brady. Might seem like a good idea for now, but it’s not going to help you 5-10 years from now…….What?!  Too soon?? 

Larissa: Hmm…Yeah, I’ve been in New England a few years now and I’m still not quite sure how to talk about Tom Brady. Anyway, does the K always come down when you stop the ACEi? 

Jeff: Not always!  The teaching point here is that there are different driving forces for each individual’s potassium balance. For example, patients with diabetes are more likely to develop hyperkalemia. 

Larissa: OOOH! Yes, I actually didn’t know this before my nephrology fellowship.  We definitely see this a lot! How does that work again?

Jeff:  So there are two reasons for this – the first is that diabetic patients start out with lower levels of insulin OR higher insulin resistance.  So the insulin surge these patients with diabetes get after a meal isn’t as robust. Less insulin, less intracellular potassium shift.  More potassium left circulating around.

Larissa: Also I think a lot of people don’t know that some patients with diabetes are in a hyporenin/hypoaldosterone state.  

Jeff: Ah yes. The so-called type 4 RTA.  

Larissa: Yes, those low aldosterone levels make the kidney much less efficient at excreting potassium.  So, say your patient has diabetic nephropathy, they’re on a RAAS inhibitor, and in this hypoaldo state…that’s basically a recipe for hyperkalemia.

Jeff: Long story short – we cannot predict how much the RAAS inhibitor is contributing to the potassium balance – each patient is a different story. So, Larissa – we talked a bit about RAAS inhibitors, but what else do you do in your practice with medications?

Larissa: So I try to ask about main offenders like NSAIDS 

Jeff: Ahh! NSAIDs! –  the nephrologist’s arch-enemy!  What most ppl don’t appreciate about NSAIDS is that they can actually cause hyperkalemia even without AKI.  

Larissa: Exactly! NSAIDs decrease renin release. Less renin, less aldo, less potassium excretion!  

Jeff: Sorry. I interrupted you before – NSAIDs get me a little riled up. What else were you gonna say?

Larissa: Don’t worry, they get me riled up too. I was going to mention antibiotics that cause hyperK! like TMP-SMX. It blocks potassium excretion in the collecting duct and that builds up that K in the body. 

Jeff: So to recap, when you’re going through the meds on a patient with hyperK go ahead and stop the RAAS inhibitor, but make sure you have a plan to get it back on board! Also look out for NSAIDs and antibiotics like TMP-SMX.

Larissa: Let’s talk about the next step. What treatments can we start to get rid of the extra potassium?  

Jeff: Sure, well, everyone knows about diuretics. But we actually have to step AWAY from the kidney to focus on the other way out of the body – the GI tract.  Potassium binders work there.  

Larissa: We won’t get into mechanisms here, but they all work in slightly different places in the GI tract and use different ions in exchange for K. 

Jeff: We’re typically using K binders in people who can’t excrete their K adequately – so think, those with advancing CKD or those already on dialysis.

Larissa: Right, let’s start with the most senior of these binders: Sodium polystyrene sulfonate, or SPS. you know it as kayexalate.   

Jeff: So SPS has been around for a really long time. What’s the data on that?

Larissa: Sadly, the data on SPS is mostly retrospective. Randomized Controlled Trials?  None. 

Jeff: Yeah, there was this one retrospective cohort study that looked at 1.8 million patients over age 66 that really made people’s heads turn.  Those who took SPS had higher rates of GI events when compared to controls – almost two times higher! And we’re not talking about nausea, vomiting, or diarrhea here.  These GI events were defined as intestinal ischemia, thrombosis, ulceration, perforation, resection, or ostomy.  Serious stuff! 

Larissa: For the most part the side effects are rare – so you shouldn’t be scared to give someone kayexalate if this is what is available to you where you work. The adverse effects are much more likely to happen in patients that have risk factors, such as active GI issues or past GI surgeries. 

Jeff: We should probably also mention that patients really don’t like SPS.  It tastes really gross.  So many of them won’t even take it on a regular basis.

Larissa: Right. All of this was enough for the medical community to long for an alternative potassium binder. 

Jeff: And finally we have them!  It took about 50 years, but now there are two different binders – patiromer and sodium zirconium cyclosilicate. They are both FDA-approved and available to outpatients.  But what do we need to know about them, Larissa?

Larissa: Alright, let’s take on patiromer first. This drug has had a couple of important trials, all named after gemstones – AMETHYST, OPAL-HK, and AMBER – with slightly different designs, but all showing that patiromer is effective at lowering K to normal levels.

Jeff: Key point here!  A significant number of patients who received patiromer in these gemstone trials were able to STAY on their ACEi’s, ARBs, and MRAs-  again, the medications that actually provide mortality and morbidity benefits!

Larissa: The main reported side effects of patiromer were hypomagnesemia and constipation – but, they are not super common and are definitely reversible/manageable.

Jeff: OK. And then there’s sodium zirconium cyclosilicate, or SZC.  These trial names have a more “inspirational” vibe, like HARMONIZE and ENERGIZE. This binder acts really fast. The data show that even after 1 dose, the potassium returned to the normal range in an average time of 2.2 hours!  

Larissa: The main side effect with sodium zirconium cyclosilicate is in its name – sodium.  Since it is delivered with sodium, SZC can cause edema, but this only happened in about about 6-14% of patients getting the higher doses of the medication.  

Jeff: But what makes the nephrologist happy is that this sodium doesn’t lead to increased blood pressure in those with edema. And, when I ask my patients about the medication itself, they tell me SZC isn’t hard to take and it’s pretty much tasteless.

Larissa: The way you see these meds used in the real world might vary a lot – dialysis patients might require it only on non dialysis days, versus your CKD patients who might be using it more frequently. 

Jeff: And you can adjust the medication dosing every few weeks until the K is within the normal range.

Larissa: These 2 new options for potassium binding, patiromer and SZC,  actually seem pretty great, especially compared to SPS.  But they are the new kids on the block, so… let me guess.  Are they really expensive? 

Jeff: They are expensive if they’re not covered by insurance.  But surprisingly, I am finding that more insurance companies are covering them. I do sometimes have to jump through hoops to get it covered.  BUT my big issue is this. Patients with significant hyperkalemia need the medication NOW…not like 1-2 days from now after the prior authorization finally comes through.

Larissa: Yeah that is definitely frustrating – but then I also try to remember how costly and stressful those ED visits for high K can be.

Jeff: Ugh.  True.

Larissa: Alright, let’s bring our discussion of K binders home. For SPS – they get a bad rap because their efficacy is not really clear but their GI side effects ARE. However, keep in mind this is a cheap medication that might also be the only one available to you when you are in a bind!

Jeff: On the other hand, the newer K binders, patiromer and SZC, look really promising.  They really do work, with minimal side effects. I’m using them more and more…especially for my patients who haven’t tolerated RAASi because of hyperkalemia. I can start back their ACEi and let them eat a healthy diet again!

Larissa: What are the cons? New drugs come with high cost and insurance coverage issues. It might not be  on the formulary at many hospitals at this point, but you can prescribe them as outpatient. 

Jeff: OK, Larissa. I think that just about covers it.  Shall we review?

Larissa: Let’s do it.  

Oh wait….hold up.  My pager is going off.  

Jeff: Really?!  Now?  

Larissa: Anyway, it’s the lab.  K+ is 6.5 in the patient with diabetes and hypertension that we saw in clinic today.  It was 4.8 on her last check a few months ago. They say it’s not hemolyzed.  I better call her…

Jeff: Wait!  This is perfect!  Let’s troubleshoot this hyperkalemia with our listeners!  

Larissa: Haha ok lets do it.

Jeff: Question #1 – Does she need to come into the Emergency Department?  Is her potassium level “too high”?

Larissa: I would say yes, based on our guidelines her K >6.0 is “too high” and she needs to go to the ED and be assessed. 

Jeff: In the ED, they can check a whole blood sample for the best accuracy. 

Larissa: And even if the potassium is STILL high, we may not see EKG changes – and that’s okay – the EKG is not a sensitive tool for detecting hyperkalemia  

Jeff: OK – Question #2 – Should you call her and tell her all about a low potassium diet? Let’s ask our discussant Dr. Joshi to weigh in.

Dr. Joshi: The renal diet that we have come to know and is taught and is recommended, and you can order at any sort of health institution is wrong. And that is not evidence-based. It is frankly dangerous. And I think ultimately contributes to confusion and worsening of complications like phosphate levels, acidosis, hyperfiltration all of these things. So in the end, I think we should feel more comfortable letting our patients eat some of these healthy foods that are good for their kidneys, eating more plant foods, um, being comfortable in counseling our patients, and then only really going into the weeds and telling people to cut back or make changes in their diet if they’re starting to run into problems and if we are not contributing to those problem.

Jeff: Yep.  I agree.  I’m not a big fan of a dietary potassium restriction.  But I do try to get a good dietary history.  We should stress portion control and moderation of higher potassium foods, especially sauces, juices, and smoothies. And if she is eating a whole lot of one of these foods, she should cut that down.  

Larissa: Nice. And finally, question #3 – What are our potassium-reducing strategies for her as an outpatient?

Jeff:  This is challenging, but we urge you to resist the temptation to stop those RAAS inhibitors long-term.  Reach for one of the new potassium binders instead, if available.  Even though SPS might be less expensive, the GI side effects and the disgusting taste of the medication make it a less desirable choice.  The data just isn’t there to support the widespread use of SPS anymore.  Patiromer and SZC have been rigorously studied and are much more effective in reducing potassium.  In her case, SZC might be the better choice now because of its rapid onset of action. That is, if you can get it covered through insurance quickly.

Larissa: And with close follow-up, hopefully we can maintain her RAAS inhibition.  If you do have to stop any of the RAAS inhibitors while getting the potassium binder started, make sure you’re prepared to start it back again soon!

Jeff: OK, now I think you’re ready to call your patient. Good luck!

Larissa; Thanks.  Oh hey!  Before we go, I have a potassium joke for you.  Wanna hear it?

Jeff: Na.

Larissa: K. 

References

 

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