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- [00:00]
A
Welcome back to Run the List, a medical education podcast in internal medicine. As a quick disclaimer, this podcast is made for educational and informational purposes only and should not be understood as medical advice under any circumstances. Before we get to the show, a quick word on the sponsors for today's episode.
- [00:16]
B
Open Evidence is the premier AI powered medical information platform for physicians and medical students. It's like ChatGPT for anyone who practices clinical medicine. Whether you have a clinical question, a question that comes up during your literature review, if you have a question that comes up when you're trying to synthesize a topic you're going to teach, you can just go to openevidence.com enter your question and it'll synthesize the answer for you while also linking to those actual articles. It's an outstanding resource. Hey everyone, welcome back to Run the List. This is your host, Walker Red, and I'm thrilled today to have Ryan Bonner as our guest on the podcast. I first had the chance to work with Ryan when we were both residents at the West Roxbury VA up in Boston and he is now an assistant professor of medicine in the Division of Nephrology and Hypertension here at the University of North Carolina. He's known around here as an innovative and outstanding educator. So I'm thrilled to have him joining us today for what's going to be a two part episode on chronic kidney disease. All right, so without any further ado, we're going to go ahead and run the list. We're going to start today with a very brief clinical vignette. Let's just imagine you're in primary care clinic and you have a new patient who's there to establish care. He is a 52 year old man named Mr. M and he's new to the area. On your review of the records prior to clinic, there really are only limited available records to look through. There is mention of chronic kidney disease and a couple other comorbidities in the chart. So Ryan, what's your general advice on how to accurately think about how we measure kidney function?
- [01:56]
C
Yeah, so thanks for having me, Walker. It's great to be here. You know, we assess kidney function or estimated glomerular filtration rate oftentimes based on serum creatinine. So serum creatinine based EGFR is what's typically reported on routine chemistries and that's suitable for most people. You know, it's easy, it's cheap, it's available, and that creatinine basically gets converted into this EGFR based off of, you know, a variety of available equations, but most commonly used now is the CKD EPI 2021 equation that doesn't include a race coefficient. And again, it's suitable for most folks, but it's less reliable at the extremes of muscle mass, which aren't uncommon. So patients with high muscle mass can overproduce creatinine and can basically show up with an elevated creatinine not related to their kidney disease. And the opposite can happen as well, where a patient with low muscle mass or disease related sarcopenia, for example, can have underproduction of creatinine, which can mask the degree of kidney disease that they have. We also know that certain medications can prevent secretion of creatinine and increase creatinine unrelated to kidney function. So the trimethoprim element of trimethoprim sulfa is a classic example. But more and more agents are falling into this category. So newer cancer agents as well as some elements of antiretroviral therapy. So to circumvent that, we also have cystatin C, which is a serum biomarker that's available to get around these issues. It has its own set of pitfalls. However, it can be included along with creatinine to best assess someone's estimated glomerular filtration rate. So for patients who have perhaps disease that places them at the extreme of muscle mass, using both statin C and creatinine can give you the best sense of what their true kidney function is like.
- [03:39]
B
Thanks so much for that update, Ryan. I remember when I was in training, just sort of like being introduced to the idea of cystatin C, not being completely familiar with it. So it's great to know that you kind of keep that in mind to and for our listeners, they can think about that, especially if they have someone who may fall into one of those populations at either end of the curve there in terms of their muscle mass. So once you have an idea of where a patient's kidney function may currently be, I know that you've taught me previously, it's important to like actually think about what is their risk of progression if they do have renal dysfunction or kidney disease. How do you sort of think about this as the clinician and then frame things for the patient?
- [04:18]
C
Yeah, I mean, it's really essential to understand that evaluation and management of chronic kidney disease isn't just about how things are right now. Right. It's not just about what the EGFR is at this moment. It's about the risk of progression because that helps guide a variety of different elements of that management. And the kidney failure risk equation has been developed as a validated way to risk stratify our patients and best understand which patients are at highest risk of progressing to end stage kidney disease. So there's kfre, which is available online. It's available as part of certain EMRs. It uses readily accessible variables so age, sex, EGFR and the urine albumin to creatinine ratio to generate a probability of a patient having advanced kidney disease to the point of needing dialysis or a transplant at two years into five years. And this can be really helpful in a variety of ways. Number one, it highlights the fact that not everybody with A creatinine of 1.5, for example, is at the same risk of progression. Right. And certainly you can have a patient with a creatinine of 2 be at lower risk of, you know, progression to end stage kidney disease requiring dialysis compared to someone who has a creatinine of, you know, 1.5, but has four times the, the albuminuria. So this can be used to identify thresholds for referral, multidisciplinary care, dialysis access creation. That's highlighted in the most recent KDIGO guidelines. It also places value on the KFRE when we think about patients who are at higher risk of progression, needing more and more aggressive treatments for their comorbidities, for example, their diabetic disease or their obesity or other things that could be contributing to their kidney disease.
- [05:57]
B
Yeah, I love that point, Ryan, just to, just to pick up on that for a second. It's like the idea of shifting a little bit from a little bit more on the prevention side, maybe like identifying those at high risk and being a little bit more aggressive with management based on the trajectory. Right. Is what I'm hearing from you and taking in more of these data points than just saying I'm going to look at the creatinine and feel reassured or worried by that.
- [06:17]
C
Yeah, exactly. Right. There's more to it. And that the urine albumin to creatinine ratio is so, so, so important in understanding this. And that's why the KFRE places a lot of value on that. Right. So if you take a 75 year old with a GFR of 59, but no albuminuria whatsoever, their risk of needing dialysis in five years is almost zero, based on the kfre. But you know, as a nephrologist, you still might get a referral for that patient based on EGFR alone. That being said, that patient doesn't necessarily need advanced nephrology care. The person who might need more advanced care is a person who has perhaps a higher egfr, but torrential albuminuria. That person would be at higher risk of progressing to end stage kidney disease or advanced kidney disease.
- [07:02]
B
Such a, such a critical teaching point there. I, I do know another point. Once you're sort of managing a patient and have an idea of what the risk of progression is, just be really thoughtful about what medications patients are on. So I'm curious what tips you have in terms of how you manage medications in patients who may be at risk for progression of their kidney disease. Again, with an eye towards sort of preventing further progression if possible.
- [07:24]
C
Yeah, there's been such a revolution in nephrology with regards to the options available for slowing the progression of kidney disease. Specifically when we think about diabetic kidney disease, which is obviously incredibly, incredibly common. I certainly can't say enough about the importance and value of collaborating and having team based care with the clinical pharmacist, if that is support that is available. That I think has really, really improved the care that I provide and that is delivered to the patients that I care for along with the pharmacy staff that I get to work with. I think it's really important, like you said, to take these patients who we have who are on evidence based, high value therapies like cases and ARBs, SGLT2 inhibitors, GLP1 receptor agonists, you know, non steroidal MRAs. There's a lot of really good treatments. We need to make sure we keep patients on them. Right. That's really hard. Which means, you know, we really need to be familiar with these meds, how we can address the side effect profile that can come up, how to manage the polypharmacy that can come up with these patients. Right? These patients, there's a lot of comorbidity comes along with chronic kidney disease, especially diabetic kidney disease. So making sure we keep an eye out for what can be prescribed, what can be simplified, organizational tools that can be used, et cetera. We do know that data supports in the recent STOPACE trial, right, continuing ACEs and ARBs as kidney disease progresses, rather than stopping them because that does actually slow the progression of kidney disease. I think another challenging element, right, is that there is some degree of financial strain certainly that comes along with some of the newer medications. So knowing what infrastructure is in place to navigate patient assistance programs, prior authorizations, that sort of thing is really important and becoming facile with that to make sure we can get patients the medications that they need and stay on them. And I think hyperkalemia is sort of another issue that's come up as well. I don't know if you'd like to take this opportunity to about that, but that's obviously something that we run into fairly often.
- [09:25]
B
That's another important point I want to make. I mean, it's just with the complexity of medicine ever increasing, I think our colleagues from the pharmacy side, and if you have that opportunity, multidisciplinary care is critical. But regardless, just empowering the patients to help understand. Okay, first of all, these are why you need all these meds. This is why they're important. Please let us know or your providers know if you do face some of those barriers you mentioned, because we often will do all we can to sort of address any barriers to getting the meds. And then, you know, I just know. I'm sure you see this all the time, a little bit of the fragmentation of care and making sure all clinicians on the team are sort of understanding why, even if it's slightly counterintuitive to some who may not do nephrology all the time, why these meds need to be continued, documenting clearly and just kind of communicating as a team. I think those are all great points, but I know you do have an important pearl because electrolyte management is one of those things that can become complicated with these folks. So how do you think about potassium specifically and what are some of your tricks you have up your sleeve for managing that?
- [10:26]
C
Yeah, and that's tricky, right, because ACEs and ARBs and MRAs are really key pillars of therapy when it comes to chronic kidney disease. When it comes to diabetic kidney disease, they're, you know, damn good blood pressure medications. However, Right. With advancing CKD and the issues that come up with potassium in that regard, you increase the risk of patients developing hyperkalemia as their kidney disease progresses. We also know that it's really important to keep patients on these. Right. Whether it's for ckd, diabetes, hypertension, like I said, heart failure. Right. So initially, I tend to really make sure these patients are on adequate diuretic therapy, thiazide, diuretics, loop diuretics. Right. Whatever the patient can tolerate, whatever the patient needs to address their volume, address their blood pressure. Certainly understanding that there is a potassium wasting component of these that's really, really valuable. There's a lot to be said about, you know, collaboration with our dietitian Colleagues to make sure that patients understand perhaps some elements of potassium in their diet that they may not recognize. And then there's also potassium binders that are pretty effective. So sodium zirconium salicylicate is a pretty effective binder. That's, you know, an exchange resin to remove potassium in the stool. And that can be effective in helping keep these patients on the therapies that are keeping them off dialysis or keeping them out of the hospital for heart failure, what have you. So those are all options that can be available? Certainly as far as patients getting a hold of the sodium zirconium salicylicate, there is a savings card that comes along with that based on their insurance. There's a patient assistance program, I believe as well. So there are some options for folks who again, do need a potassium binder to stay on some of these more or less life saving therapies.
- [12:08]
B
Right, Absolutely. I wanted to ask you if there's some common pitfalls you see specifically, are there some medications that we need to think about dosing differently or avoiding altogether in patients who have renal dysfunction? I'll be the first to admit during residency and even now when I'm mainly practicing gi, there's sometimes where I will think about an indication for a medicine, not forget the ckd, but have it in the back of my mind for a moment and then have to remind myself or look it up and be thoughtful about whether the patient can be on it or whether it needs to be dosed much more intentionally than I would otherwise. So I'm sure you've seen some things go awry. So what are some, some common meds you want folks to keep in mind?
- [12:48]
C
Yeah, well, you know, with, with you being in GI and me being in nephrology. Right. The NSAIDs are typically off limits either way.
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B
So we're on the same page there.
- [12:55]
C
Exactly, exactly. And that, you know, that's the first one I'll talk about. I. The main concern with NSAIDs from my standpoint, is that it does impair your kidney's ability to autoregulate its perfusion. So patients who are taking a lot of NSAIDS around the clock and become volume depleted can't necessarily adjust in the same way and are at more risk of injury from that same insult when they might not have been at risk of that injury otherwise. And that gets amplified certainly in patients who are on angiotensin receptor blockers or ACE inhibitors. So, you know, NSAIDs really need to be carefully used, especially with worsening kidney function in patients who are on those meds or are at risk of volume depletion. That doesn't include all the other, you know, risks that come along with it. They also, you know, can drive some hyperkalemia elements that can lead to salt retention, you know, diuretic resistance. There's a whole bunch of stuff that fall into the category of why NSAIDs aren't a great option in kidney disease. There are, right, medications that can sort of aggravate the sequelae of ckd, right. Promote some hyperkalemia. So trimethoprim sulfamethoxazole is one. In patients with ckd, especially those who are on angiotensin receptor blockers or ACE inhibitors, that is not an optimal choice and can really lead to some pretty serious hyperkalemia. Again, NSAIDs are in that category as well. There's certainly medicines where, especially for, you know, analgesia or sedation, that can be problematic in chronic kidney disease as well, with higher risk, certainly for adverse consequences. So tramadol morphine is in that category. Gabapentin needs to be dosed really carefully as well. Baclofen is really quite challenging and can be really, really unsafe, especially in advanced kidney disease. And that's even at therapeutic doses. You can develop baclofen toxicity with chronic kidney disease, even at what otherwise would be a well tolerated dose in someone who does not have kidney disease. So baclofen is a. No, no. Certainly in patients with advanced kidney dysfunction.
- [14:52]
B
Baclofen is actually the one that a couple times I've been reaching for it and realized it's just not safe even with, not even that advanced of kidney disease. And so just to recap what you just gave there, you gave NSAIDs, some antibiotics, some common things to do in the outpatient setting, like gabapentin, but also need to be thoughtful sort of on the inpatient side with sedation or analgesia. As well. Taking all this into consideration, I think if we fast forward in time, we've done a nice job managing our patient. We were able to meet him in clinic, ascertain an idea of not only what his current kidney function is, but what his risk of progression was, make sure that he was on guideline directed medical therapies, avoid any medicines that would have risked his progression of kidney disease, and he's done quite well. Before we wrap up, we always ask our guests just to give a couple of last pearls or takeaways you want our listeners to remember for managing patients with ckd.
- [15:43]
C
Yeah, absolutely. I think the first is identifying or optimally characterizing your patient's chronic kidney disease, even irrespective of the driver, which itself is important by having an accurate assessment of their kidney function and obtaining a urine albumin to creatinine ratio so you really understand what their risk of progression is. I think my second takeaway is that we have really good medicines for chronic kidney disease, especially that related to diabetes, and it's important to get people on those medications and certainly keep them on once we get people started. Lastly, you know, whenever you're starting a patient who has CKD on a particular medication, always making sure that you're dosing that medication appropriately and keeping a close eye out for side effects that may not present themselves in someone who has normal kidney function.
- [16:29]
B
Amazing. Ryan, thanks so much for those summary takeaways and thank you so much for being here as a guest. We so appreciate it. With that, we'll go ahead and wrap up this episode and we will see you all back here for CKD Part 2.
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A
Some content from this episode was generated with the assistance of artificial intelligence.