Speaker 1 00:00 Alex, welcome to HelixTalk, a podcast presented by the Rosalind Franklin University, College of Pharmacy. We're hoping that our real life clinical pearls and discussions will help you stay up to date and improve your pharmacy knowledge. This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - Dr. Abel 00:29 And now on to the show. Dr. Sean Kane 00:31 Welcome to HelixTalk. Episode 37 I'm your co host, Dr. Kane, and I'm Dr. Patel. Unfortunately, we don't have Dr. Schuman here today, but he'll be with us with a future episode today, Speaker 2 00:41 we're going to talk about a very controversial topic, and something that should be a mastery of pharmacist, and that is calculating creatinine clearance, or how should we estimate the renal function in general? Dr. Sean Kane 00:54 And we'll talk more about this. But creatinine clearance is one of those things that pharmacists do all the time for drug dosing purposes. And what we mean by that is that when we want to analyze someone's renal function, we can estimate it using something called creatinine clearance. And obviously, if a drug uses the kidney to be eliminated from the body, if your kidneys don't work as well, then we have to make adjustments for that. So if you have a really low creatinine clearance, it means that you have a low renal function. Maybe you don't need as much of a medication because that medication is going to stick around longer. Speaker 2 01:24 And so you were saying, Dr. Kane, that the reason we teach students all the pharmacokinetic and dynamic of medications and want them to know those parameter is because it is ultimately resulting into the drug response based on how well the kidney function is correct Exactly. Dr. Sean Kane 01:41 So if we think about creatinine clearance, we kind of have to step back a little bit and talk about what the kidney does and how it works. So really, when we think about creatinine clearance, we're actually talking about glomerular filtration rate or GFR. But we use creatinine clearance as a convenient surrogate, because it's really difficult to measure true glomerular filtration rate. Speaker 2 02:01 And so when we talk about this process, you know, we have blood goes under a pressurized glomerulus, and basically the tubule system that's attached thereafter collects all the waste, and that waste product is what we call urine, yeah. Dr. Sean Kane 02:16 And so that post glomerulus area, which is are the tubules you have, the loop of Henle and the proximal and distal tubule and things like that. The job of that tubule system is to reabsorb things that got filtered out during glomerular filtration. So as an example, your body loves sodium, so lots of sodium ends up in the tubule system, but the body will actually reabsorb something like 98% of the sodium in the tubules back into your blood, and Speaker 2 02:41 there are a lot of pumps and receptors located in the tubule to finish this function. And there are few substances. They're completely actively secreted in these tubules from the blood. One of the example is creatinine. Dr. Sean Kane 02:56 And this is one of those kind of minute details that really doesn't matter, except on a textbook in that because we actively secrete creatinine into the tubule system, it's not an accurate measure 100% in terms of your glomerular filtration rate, it actually overestimates your GFR by about 10% because of this active secretion into the tubule system. But for drug dosing purposes, that 10% really is not that relevant, and it gets us close enough to what a true GFR is. Speaker 2 03:24 And so when you talk about GFR, Dr. Kane, you mentioned that you're using it for the drug dosing purposes. So can you break it down and explain, you know, if I had a patient who had a high GFR versus a patient who had low GFR, how would a drug react? Sure. Dr. Sean Kane 03:40 So let's pretend that we had a drug, that 100% of the drug left the body in your urine. So your kidney gets rid of 100% of the drug. If your GFR is like 120 mls per minute, we measure GFR in mls per minute, which is basically how much blood is cleared or cleaned in a given unit of time. So if your GFR is 120 if your GFR suddenly went from 120 to 60, you've effectively halved the GFR, the amount of filtered blood that you have per unit of time. So in other words, if you're at 120 and you go to 60, that also means that you're going to get rid of half as much drug in the same period of time. We have to account for that by giving you less drug, because your kidneys Speaker 2 04:21 aren't working as well. That's where this drug dose adjustment comes in play, exactly. Dr. Sean Kane 04:25 And this is a huge role for pharmacists, because this is one of those really, really important details for especially for drugs that have a narrow therapeutic window where the balance between toxicity and efficacy is really small. It's hard to hit that target. This is where pharmacists really shine in identifying patients that do need renal adjustments and making appropriate recommendations based on the renal function. Speaker 2 04:47 And like we mentioned, the Creatinine clearance that is used in replacement of the GFR is based off of the Creatinine calculation. And we mentioned creatinine is one of the substance that active. Is secreted into the tubule. So like you mentioned, Dr. Kane, I repeat it again. It basically overestimates the GFR by about 10% Exactly. Dr. Sean Kane 05:09 And if you look up in any drug reference where they have renal adjustments, you'll quickly see that that 10% usually isn't going to make a big difference in terms of how you actually adjust the drug dose. So clinically, we're okay with this 10% variation, because creatinine clearance is close enough to GFR that it gives us a good estimate. And that's really important. It's an estimate of your GFR, your glomerular filtration rate. Speaker 2 05:33 It's not a true representation of GFR Exactly. And so curiosity would be where this creatinine is coming from. So creatinine, basically comes from a substance called creatinine, and then, from what I know, a creatinine, creatinine goes to the liver and it gets converted into the Creatinine. Dr. Sean Kane 05:52 Yeah, so muscles make creatine that gets converted to creatinine in the liver, and then that gets eliminated by your kidney. So the reason that that matters is that if you have a lot of muscle you're going to make more creatine to get converted to creatinine. If your liver doesn't work very well, then you're not going to make much of that conversion. And if you're really deconditioned, so if you're an elderly patient in a nursing home and you're bed bound, you're not going to have a lot of muscle mass to be able to produce this creatine that gets converted to creatinine. Speaker 2 06:20 So that's a background on GFR and creatinine clearance. Now let's talk about how there are some the methods we can use to calculate this creatinine clearance. The first one that comes to mind is Cockcroft-Gault equation. That's like the gold standard. Every we ask every students to memorize this equation, and we've used it for drug dosing because in the clinical trials, the manufacturers have used the same parameters, and so we're using it in the clinical practice as well, exactly. Dr. Sean Kane 06:47 And what's really interesting about Cockcroft-Gault is that it was published in 1976 so it's a pretty old method in terms of when it was published, and it only included about 250 men, so there were no women in the trial, and the kinds of people that they included were people that were close to their normal or ideal body weight, so they didn't have a lot of fat mass to them, and also they had very stable renal function. So these weren't critically ill patients. These were people that had very rock solid, stable renal function, in the sense of their their serum creatinine was not changing very much. Speaker 2 07:20 So you're saying that ideally we should use this equation just in men who are non obese and have stable renal function. Dr. Sean Kane 07:27 That would be great if we only had those kinds of patients in clinical practice. But unfortunately, we have obese patients. We have women that we actually have to dose drugs in. So we've actually extrapolated this Cockcroft-Gault equation to all of these other populations. And one of the problems that we've had is that over the decades, from 1976 onward, because these other populations weren't extensively studied, many people have kind of branched off and done different things to this Cockcroft-Gault equation to try to make it appropriate for these different patient groups. Speaker 2 07:57 And so what do they do to make this equation applicable to, let's say, your female population. Dr. Sean Kane 08:02 Yeah, so if you actually read the Cockcroft-Gault paper, it's pretty funny that they say, No, we didn't include any women in our trial. But women have about 15% less muscle mass, so 15% less creatinine that they produce, therefore we should just reduce them by 15% or multiply their creatinine clearance by point eight five, and that would give you that 15% reduction. And that Speaker 2 08:23 is why the equation is a little bit different when we are using it for our female patient versus our male Dr. Sean Kane 08:27 patient, exactly. And interestingly, they were actually pretty accurate. So decades after Cockcroft-Gault was published, they did look at whether this 15% reduction was appropriate or not. It depends on the paper you look at, but roughly speaking, about 15% does appear to be appropriate and does fairly accurately estimate the difference between men and women. Speaker 2 08:47 So this was a dart that was thrown in dark, but it hit the mark exactly close enough that we're okay with it for drug dosing. Gotcha. So what about then the patients who do not have stable renal function, Dr. Sean Kane 08:58 so for those that have rapidly changing creatinine values. Cockcroft-Gault doesn't do a very good job in estimating what their creatinine clearance is. A great example of this is Dr. Patel, if you opened up my belly and took out my kidneys right now, if my creatinine is one right now, in a couple hours, it might just be 1.2 or 1.3 but I actually have no GFR at all because I have no kidneys Right, right? So there's some lag in the production of creatine from the muscle that gets converted to creatinine, getting to steady state of serum creatinine, and the worse your acute kidney injury is, the longer it takes for you to see the end result, or the steady state value of the serum creatinine. Speaker 2 09:35 So you're saying that creatinine is freely filtered from the kidney. If the kidneys are not working, then the Creatinine will back up in the serum, and we will see higher serum creatinine value Exactly. Dr. Sean Kane 09:47 But it takes time for that to manifest. So the serum creatinine value is going to lag behind your actual glomerular filtration rate until you get at steady state of where your renal function is going to be at. As we've always said, this is. An estimate, and we use creatinine as a way of estimating renal function, but it's not perfect, and these acute kidney injury patients are a great example of when it's not perfect. So what we do for those people is we can still use Cockcroft-Gault, but we have to understand that it's only a snapshot, and then we have to clinically evaluate kind of the velocity of change. So if my creatinine today is one and tomorrow is two. That's a pretty impressive bump in creatinine over a very short period of time. I'm going to dramatically reduce whatever Cockcroft-Gault tells me as my renal function. Conversely, if I am at two today and I go to one of a serum creatinine tomorrow, I'm going to dramatically increase what Cockcroft-Gault says because my serum creatinine is dramatically improving. Speaker 2 10:41 And how does that reflect to a dosing of a medication? If you can give us a couple example, Dr. Sean Kane 10:46 yeah, so you know, we see acute kidney injury extremely commonly in the ICU. We also use antibiotics very commonly in the ICU. So if I'm giving a patient vancomycin, and on day one, their creatinine is two, and then day two, it goes down to one, I'm definitely going to increase their vancomycin dose, even if their Cockcroft-Gault doesn't really justify that dose increase yet. Speaker 2 11:06 Okay, well, that kind of gives us an idea of what you just talked about in terms of how certain creatinine and creatinine clearance doesn't really match right away, there is a little bit lag and so third patient population that was not part of the original Cockcroft-Gault study was the obese patient. So I do know that there is all this term that being thrown around. You know, ideal body weight, actual body weight, adjusted body weight. And people are really confused as to what weight to use, so let's kind of break it down for them. Dr. Sean Kane 11:35 Yeah. So one key thing to think about is that fat tissue doesn't make creatine. So you don't produce creatinine from fat body mass. Speaker 2 11:44 So you're trying to say that, let's say, if we have an obese patients, we have to separate their fat and then just look at the lean mass, the muscle mass, and based off their renal functions, on that Dr. Sean Kane 11:55 mass Exactly. And if we could kind of do that, you know, physically, it would be great, but we can't. So then we have to use equations to estimate what amount of their body mass is fat mass, and then we actually give them kind of a bump in presumed muscle mass, because they have to move around all this adipose or fat tissue, Speaker 2 12:12 okay, and what kind of things or tools we would utilize to calculate that lean body mass. So the Dr. Sean Kane 12:19 ideal or lean body mass is based on your height and your gender, and there's equations for this. And then once you figure that out, there's something called an adjusted body weight, where you kind of take part of their lean body mass, or their ideal body weight, and then you add that to a portion of the rest of their body mass. And again, there's an equation for an adjusted body weight that I'd encourage the listeners to take a look at, but this is one of the best ways that we can semi accurately estimate what is the patient's creatinine producing mass. Gotcha. Speaker 2 12:49 So it's going to be different in terms of who we call an obese patient, right? So we're trying to ideally use the ideal body mass. But then in obese patients, I've heard their actual weight should not be used, because you mentioned there's a lot of adipose tissues there, and sometimes there are issues with using ideal body weight in those obese patient too. So what do we do for them? Dr. Sean Kane 13:13 As you said, Neither actual or ideal weight are appropriate if you're a very obese patient. So we do use an adjusted body weight equation, and we plug that one into Cockcroft-Gault. And there's been other equations that have been developed specifically for obese patients. The Salazar equation from the 1980s is a very popular equation, but it turns out that if we just use adjusted body weight with the Cockcroft-Gault formula, that's the most accurate way to estimate renal function in these very obese patients. Speaker 2 13:40 So we just need to tweak the calculation a little bit, and no need to go to a different whole, nother, different calculation or equation to measure proper creatinine clearance Exactly. Dr. Sean Kane 13:48 And we have good evidence to support this practice of adjusted body weight as opposed to ideal or actual or using some other equation that's been developed. Speaker 2 13:56 Okay, so if I gathered all that information correctly, I'm gonna say if the patients who are below their ideal body weight, we're going to go ahead and use their actual body weight. For patients who are in their ideal to up to 20 or 30% of their ideal body weight, we're going to go ahead and use the ideal weight. If they're above 30% than their ideal body weight, then we're going to use the adjusted body weight? Do I have it correct? Dr. Sean Kane 14:23 You've got it perfectly correct. So a great example is that if you're a very, very underweight patient, it wouldn't make sense to use your ideal body weight, because we're giving you muscle mass in the equation that you don't actually have, right? So if you're 30 kilograms and you're six feet tall, we're going to treat you as if you have 30 kilograms of mass. And conversely, if you're a very, very large patient, we're going to use that adjusted body weight, because the fat tissue isn't making creatinine. And if you're somewhere in between those two, then we're going to use your ideal body weight, which would be appropriate and the best estimate of your renal function. Speaker 2 14:52 That makes a whole lot of sense. Now, just like we have convergence for the ideal body weight, like you mentioned, this ideal body weight calculation, u to. Realize this patient's height, patient's weight and the gender you mentioned. Sometimes we have patients who are not five feet tall, because that's what's used in the equation, and it's depending on the institution I work for, Aurora healthcare, and what they do is, every inch they are shorter than five feet, they will subtract 2.3 kilograms out of their ideal body weight, and that's the equation that they use. Sometimes, some clinicians would use 1.2 kilogram reduction per each inch that patient is below than five feet. Dr. Sean Kane 15:36 Yeah. And unfortunately, this is one of those things that we don't have great data of what to do, but it does make sense to reduce some value for those who are vertically challenged, but in terms of what is the most appropriate metric to use, we don't really know. And for those of you who don't know, the terminology of ideal body weight is a bit of a misnomer. So when we say ideal to me, it sounds like something that you should strive towards, but really lean body mass is probably a more appropriate term. So the idea of ideal body weight comes from insurance tables that really weren't intended for estimating lean body mass and really weren't intended for drug dosing purposes. But it just happened that over time, we kind of developed these equations from these insurance databases into what we use today, and it turns out that they're close enough, again, to estimate, as opposed to be super accurate in renal function. And if you're really interested, I'd encourage anyone that wants to know more about the ideal body weight equation to take a look at an article called The origin of the ideal body weight equations. This was published in Annals of Pharmacotherapy in the year 2000 and it's a great historical perspective of where this equation came from and how we've kind of repurposed it for a lot of things that it really wasn't intended for in the first place. Speaker 2 16:49 That is very neat history that's there behind so Dr. Kane, we talked about using the Cockcroft-Gault equation for female patients, for patients who have unstable renal function, patients who have, you know more adipose tissue distribution than your normal patient. What about old patient? I know that their muscle mass over the time as they age decreases, and how, how realistic would be for us to use Cockcroft-Gault equation in our geriatric patient? Dr. Sean Kane 17:18 What a great question, and this comes up so often when we're trying to dose antibiotics for older patients, or, you know, dose any medication that's really eliminated again, back in 1976 when the Cockcroft-Gault came out, this wasn't a big emphasis in terms of analyzing these 85 year old nursing home patients. You know, that wasn't the patient population study. So over the decades, pharmacists primarily, have come up with different ways to kind of get around the fact that elderly patients have less muscle mass and try to account for that. One of the most common scenarios done is to round a creatinine value to one. So if a patient who's elderly has a creatinine of point five, you assume that it's artificially low and not representative of their GFR. So you just round that point five Speaker 2 18:03 to one, does this mean? Then you're decreasing their creatinine clearance by 50% by, you know, increasing this from creatinine, Dr. Sean Kane 18:10 and then exactly, so you basically give them a handicap for their age. But the problem comes when you're actually doing this rounding. If you round a point five to one, that's a 50% change, right, right? So if you do a point seven to one, that's a 30% change. So you haven't treated those two patients equally, right? What do you do when the patient's creatinine is 1.2 you don't round down to one, you don't increase it by 30 to 50% and that's really where the weakness of this method comes in, is that it doesn't treat patients equally. It just takes those with low creatinine values, brings them to one, whether it's a dramatic shift in their creatinine value or just a very small change. Speaker 2 18:46 That is very interesting, because from where my residency training was, we were told, you know, point seven, you can run it up to one. Anything that's below point seven, you use the actual value. And again, this was based off of not a whole lot of literature that's out there. Dr. Sean Kane 19:02 Yeah, but in all fairness to anyone that does round creatinine values, we just don't have good data of what to do. Some of the best data that we do have says that a 30% handicap, or multiplying by point seven and those cachectic, very old patients is probably a reasonable way to account for this. And this would be the equivalent of rounding a point seven to one, which would be a 30% change. And that's probably a fair way to account for this, but realizing that in those old cachectic patients, when you're doing a Cockcroft-Gault estimate, your margin for errors can be much larger than for a normal body weight, middle aged male, where you're going to be much more accurate. Speaker 2 19:40 So all in all, when we talk about different patient population, let's talk about the accuracy of Cockcroft-Gault. I know you said there is a little bit lag between the true serum creatinine value versus the Cockcroft-Gault, but with the true grain of salt, you know, let's say I'm I have a medication, and this happens a lot to me when I'm dosing bisphosphonate. In the clinic, I have a patient whose creatinine clearance is 32 and for certain bisphosphonates, the cut off it's 30 What do I do? Do I say no to them on bisphosphonates and I call them, you know, renally handicapped, like you mentioned. Or do I go ahead and put them on and subject them to higher toxicity? Dr. Sean Kane 20:20 This happens so commonly because a creatinine clearance cut off of 30 is kind of what you'll see for most renally eliminated medications. So the manufacturers have, for a variety of reasons, picked 30 as this magical cut off for most drug dosing adjustments. The problem, though, is that when you have that creatinine clearance of 32 your margin of error is probably plus or minus five, so that creatinine clearance of 32 could be as high as 37 or as low as 28 and you're really riding the line then of whether you adjust or not, and clinically, what we should be doing for those patients is making a clinical judgment based on what would happen if you gave too much or too little of the medicine. So as an example for an antibiotic, if it's a really, really sick patient, you should probably be more aggressive. If it's a bisphosphonate, you should probably look at their fracture risk over time and how aggressive you want to be with them, what their risk of ONJ would be osteonecrosis of the jaw. So kind of a risk benefit. I think that when you ride that line, or when you're really close to the cut off, it should be a patient specific decision, as opposed to a black and white they're 32 therefore I can give it, or they're 29 therefore I cannot give it. I think that's probably the wrong approach. Speaker 2 21:28 So just simply plugging and chugging the information in the equation and using that number is not enough. We need to kind of insert our clinical knowledge patient factors into that decision making Exactly. Dr. Sean Kane 21:40 And one common scenario that I see with pharmacy students is that they'll report a creatinine clearance, as you know, something all the way out to the 100th decimal point. So 29.53 and the reason that I don't like that is, I think it really gives the impression that we have a very accurate estimate of renal function when we really don't. So for me, clinically, I'm very comfortable rounding to the nearest five, as opposed to the nearest one, or anything like that. So certain clinicians are more or less comfortable, but in the ICU, where I see so much acute kidney injury, I just know that I'm going to have a rough estimate no matter what I do. And I'm comfortable enough with that that I start thinking about these other patient specific factors as opposed to just the number itself. Speaker 2 22:21 Gotcha All right. So that was a great talk on using the Cockcroft-Gault equation, and we know some strengths and some limitations of using that equation. Are there any other equations that we can use to represent GFR? Dr. Sean Kane 22:34 Yeah, absolutely. So we've gone through a number of different patient groups that are basically poor candidates for Cockcroft-Gault, but we have to use them, because that's what the's what the manufacturers have used to describe renal adjustments. So after Cockcroft-Gault came out, one big push was called the MDRD equation, and this was published in the late 1990s and really it was intended to risk stratify chronic kidney disease patients. So if you had a creatinine clearance less than 60, this was really good at saying if you had stage one or stage two chronic kidney disease, so it wasn't really intended at the time to look at drug dosing for renal impairment, but it is more accurate than a traditional Cockcroft-Gault equation is. But what happened was, because it doesn't estimate creatinine clearance, if it's above 60, a new equation was published called the CKD-EPI equation. This was around 2009 and this is accurate, and it's also more appropriate for those with better renal functions. For creatinine clearance greater than 60. The problem, though, is that both of these equations, MDRD and then its update, CKD-EPI, really are only intended for estimating renal function for chronic kidney disease staging, as opposed to renal dosing, because manufacturers aren't using these equations to describe how to adjust a drug in someone with renal impairment. Speaker 2 23:52 So you're saying that MDRD And the CKD-EPI are used more for diagnostic and staging purpose, versus the Cockcroft-Gault that should be utilized as the dosing equation Dr. Sean Kane 24:05 exactly, but there's certainly a big push, especially from OCD pharmacists such as myself, that we know that Cockcroft-Gault isn't accurate. It would be great if drug manufacturers could start using some of these more updated, more appropriate and more accurate equations, like CKD-EPI to describe drug dosing adjustments and renal impairment. Speaker 2 24:23 Yeah, that too. And you know, I've noticed new drugs and realm of diabetes therapy that have come across, and they're using eGFR as one of the marker instead of using Cockcroft-Gault creatinine clearance. So for those though, calculation is very easy, because your complete metabolic panel, or your basic metabolic panel, it's going to yield an eGFR. So there are some drugs that are following the eGFR based titration. And just so the viewers know the eGFR at least in the clinic I work in the lab I work with different sheets between all the patients eGFR versus the African American patient's eGFR. So you kind of really have to look at the patient's race and then use the appropriate eGFR to estimate their renal function. Dr. Sean Kane 25:08 And the cool thing is that these eGFRs are using MDRD or CKD-EPI, and they do all the math for you. So if you look at CKD-EPI, the equation is actually incredibly complicated compared to Cockcroft-Gault, but it's intended to be an electronic calculation that you just don't have to worry about, and they give you a number, and that's it. And one of the advantages of something like MDRD and then later CKD-EPI is that they did implement race, and race does matter in terms of figuring out a patient's actual GFR. So not only are they looking at height, weight and age and gender, but they're also looking at race, which does matter, and that's why some of these newer equations are more accurate. Speaker 2 25:46 Well, we only wish that the manufacturers make that shift anytime soon. Dr. Sean Kane 25:50 Yeah, and we're seeing it a little bit like you said. And I mean, if you think about it, what a great disease state to focus on, like diabetes, when things like CKD are very common in that patient population, absolutely. Well, let's cover some of the big take home points from today's talk about creatinine clearance and Cockcroft-Gault and estimating renal function. Speaker 2 26:08 So for drug dosing, we use Cockcroft-Gault equation, and we get a value that's creatinine clearance. Dr. Sean Kane 26:14 And it's important to note that because we're using serum creatinine as the thing in the blood that we measure to estimate GFR. Anything that modifies creatinine unrelated to GFR is going to mess up your calculation. So if they're very, very large, very, very small, if they don't have muscle mass, or they have a lot of it, or they have hepatic impairment, that's going to change and falsely either increase or decrease your serum creatinine value, which will thereby impact and falsely elevate or decrease your creatinine clearance. Speaker 2 26:43 And same thing goes along in patients who have acute renal injury. So you kind of have to look at, not just a snapshot, and that's what your creatinine clearance or Cockcroft-Gault will provide, but you kind of have to look at, what's the velocity, or, you know, where were they baseline, and where are they now? Or where were they, you know, up high at two versus what are they now today? So it will give you a clinical judgment. Again, like you mentioned, this should be estimates, a rough estimate, and not an accurate Dr. Sean Kane 27:12 calculation Exactly. And then for those obese patients, we should be using an adjusted body weight, actual body weight, ideal body weight. Are definitely no nos for the obese patient population, and then some of the older equations, like the Salazar equation, has been shown to not be as accurate as just using the run of the mill Cockcroft-Gault in conjunction with the adjusted body weight. Speaker 2 27:31 And for our older adults, geriatric patients, you know, instead of rounding that certain creatinine to one, you rather want to decrease the creatinine clearance by 30% and that's, like you said, it's a little bit accurate representation of what their true renal Dr. Sean Kane 27:47 function is, yeah. And I think that globally for all of these patient populations, it's important to remember that this is just an estimate, and you have to use other patient factors to decide for drug dosing whether you want to be more aggressive or less aggressive. I think that that gray area, this is where that gray area of medicine comes in, where you could argue that even though the creatinine clearance is 29 I'm gonna give them the bigger dose, as if their creatinine clearance was above 30. And then finally, the last Pearl is that we do have better, more accurate estimates of renal function. So eGFR is either based on MDRD equation or CKD-EPI equation. And these are great because there's no math involved. It just comes up on your BMP. But drug manufacturers have been slow to adopt these when describing renal adjustments for their drugs. So it's something we'd love to see more of, and we probably will see more of, but it's going to take time Speaker 2 28:37 and Well, we hope that they stick to more accurate of the equations Exactly. Dr. Sean Kane 28:42 So with that, we'll go ahead and sign off. For those of you who want to visit us online, we're at HelixTalk.com we're also available on iTunes. If you search for HelixTalk, we love five star reviews. So with that, I'm Dr. Kane and I'm Dr. Patel. Unknown Speaker 28:55 As always, study hard. Narrator - Dr. Abel 28:57 Thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science. For more information about the show, please visit us at helixtalk.com you.