Estimating Kidney Function in Chronic Kidney Disease

Listen in as our expert panel untangles the latest recommendations for using equations to estimate kidney function. You’ll hear their insights on when and how to use creatinine, cystatin C, or both to help safely adjust medication doses in kidney disease.

Special guests:

• Erin F. Barreto, PharmD, PhD, FCCM, FASN, BCCCP
  • Associate Professor of Medicine and Pharmacy
  • Mayo Clinic
• Tracy Anderson-Haag, PharmD, BCPS, BCTXP
  • Clinical Pharmacy Specialist-Transplantation
  • Residency Program Director, PGY-2 Solid Organ Transplant
  • Hennepin Healthcare

None of the speakers have anything to disclose. 

This podcast is an excerpt from one of TRC’s monthly live CE webinars, the full webinar originally aired in June 2026.

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TRC Healthcare offers CE credit for this podcast. Log in to your Pharmacist’s Letter, Pharmacy Technician’s Letter,or Prescriber Insights account and look for the title of this podcast in the list of available CE courses.

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The clinical resources related to this podcast are part of a subscription to Pharmacist’s Letter, Pharmacy Technician’s Letter, and Prescriber Insights: 

• Chart: Medications and Kidney Function
• Chart: Lab Monitoring for Common Medications
• Website: National Kidney Foundation eGFR Calculator
• Chart: Lab Monitoring for Common Medications: Condensed Version

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Transcript

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00:00:07 Tracy Anderson-Haag

So Cockcroft-Gault validated an equation to be able to estimate creatinine clearance without actually doing a measured collection of urine.

00:00:17 Tracy Anderson-Haag

Unfortunately, this was done in only 249 patients and they were all white males from Canada.

00:00:24 Tracy Anderson-Haag

So a very homogenous, limited, non-diverse group of patients.

00:00:29 Tracy Anderson-Haag

This was also done over 50 years ago during a time when creatinine was not standardized in the lab.

00:00:38 Erin F. Barreto

90% of the drug dose choices you're going to make are going to be the same because of the point that was raised, which is we're not trying to dial in 2 mils per minute for making medication decisions.

00:00:49 Erin F. Barreto

We're trying to dial in a category which is 20, 30, 40 mils per minute wide.

00:00:55 Erin F. Barreto

I think perfection sometimes in this is the enemy of good.

00:00:58 Erin F. Barreto

I think in general, make the move to eGFR creatinine, most of your decisions are not going to be affected, and those that are probably going to get better and more accurate with this change.

00:01:13 Narrator

Welcome to Medication Talk, an official podcast of TRC Healthcare, home of Pharmacist's Letter, Prescriber Insights, and the most trusted clinical resources.

00:01:21 Narrator

On this episode, listen in as our expert panel untangles the latest recommendations for using equations to estimate kidney function.

00:01:30 Narrator

You'll hear their insights on when and how to use creatinine, cystatin C, or both to help safely adjust medication doses in kidney disease.

00:01:39 Narrator

Our guests today are Dr. Erin Barreto, an associate professor of medicine and pharmacy at Mayo Clinic.

00:01:46 Narrator

and Dr. Tracy Anderson-Haag, a transplantation clinical pharmacy specialist at Hennepin Healthcare.

00:01:53 Narrator

This podcast is an excerpt from one of TRC's monthly live CE webinars.

00:01:57 Narrator

Each month, experts and frontline providers discuss and debate challenges in practice, evidence-based practice recommendations, and other topics relevant to our subscribers.

00:02:07 CE Narrator

And now, the CE information.

00:02:11 Narrator

This podcast offers continuing education credit for pharmacists, pharmacy technicians, physicians, and nurses.

00:02:18 Narrator

Please log in to your Pharmacist's Letter, Pharmacy Technician's Letter, or Prescriber Insights account, and look for the title of this podcast in the list of available CE courses.

00:02:28 Narrator

None of the speakers have anything to disclose.

00:02:33 Narrator

Now, let's join TRC editors and clinical pharmacists, Drs. Stephen Small and Sara Klockars, and start our discussion.

00:02:42 Steve Small

Tracy, can you start us off here by generally telling us about chronic kidney disease?

00:02:47 Tracy Anderson-Haag

Chronic kidney disease is generally an issue where we have a problem both structurally and functionally with kidney function.

00:02:55 Tracy Anderson-Haag

And as pharmacists, we oftentimes think about that as the ability to filter things, filter medications that go through the kidney.

00:03:02 Tracy Anderson-Haag

But it also has to do with the ability to handle proteins, and there are a lot of neurohormonal effects that can happen with kidney dysfunction as well, impacting other issues like bone and mineral disease and anemia.

00:03:15 Tracy Anderson-Haag

Usually this needs to be present for at least three months documented in the medical record, and it's generally measured both through lab testing through the blood and also lab testing through the urine.

00:03:26 Steve Small

And I'm glad you mentioned the complications with CKD since there are many.

00:03:32 Steve Small

If kidney function is severe enough, patients may need dialysis to filter waste from their blood, and some may need a kidney transplant if they're eligible.

00:03:40 Steve Small

And certain factors can increase a patient's risk for CKD, things such as diabetes, heart failure, and hypertension, which is why proper management for these conditions is key to protect kidney health.

00:03:53 Steve Small

Plus, if patients develop CKD, we can determine the severity by the glomerular filtration rate, or GFR.

00:03:59 Steve Small

And as Tracy mentioned, GFR affects medications that are cleared through our kidneys.

00:04:04 Steve Small

And we usually rely on estimated GFR or eGFR using equations that we'll talk about today.

00:04:10 Steve Small

And I'm sure a big question a lot of our audience is asking right now is the history behind the Cockcroft-Gault equation and using it for drug dosing, because that kind of sets the stage for what we'll talk about with new equations.

00:04:23 Steve Small

But Tracy, could you give us some of that history to help out our audience?

00:04:28 Tracy Anderson-Haag

Yes. So over 50 years ago, when we did not have the science to be able to accurately or correctly measure glomerular filtration rate, which is the best measure of kidney function

00:04:40 Tracy Anderson-Haag

We used a proxy, which was creatinine clearance, or basically creatinine that was cleared in the urine, recognizing that that's an overestimate because we know serum creatinine is not only filtered, it also undergoes tubular secretion.

00:04:55 Tracy Anderson-Haag

So creatinine clearance will overestimate our glomerular filtration rate.

00:05:00 Tracy Anderson-Haag

But this is what we had available.

00:05:02 Tracy Anderson-Haag

And so Cockcroft-Gault validated an equation to be able to estimate creatinine clearance without actually doing a measured collection of urine.

00:05:11 Tracy Anderson-Haag

Unfortunately, this was done in only 249 patients and they were all white males from Canada.

00:05:18 Tracy Anderson-Haag

So a very homogenous, limited, non-diverse group of patients.

00:05:24 Tracy Anderson-Haag

This was also done over 50 years ago during a time when creatinine was not standardized in the lab.

00:05:31 Tracy Anderson-Haag

And so the creatinine values back in that time were higher than they are now by about 12%.

00:05:38 Tracy Anderson-Haag

And so we still don't have those samples.

00:05:41 Tracy Anderson-Haag

We can't go back and validate any of this data with current lab use or a more diverse patient population.

00:05:48 Tracy Anderson-Haag

And so because all we had was Cockcroft-Gault, this has been used for drug dosing for now

00:05:53 Tracy Anderson-Haag

50 years, and we are recognizing the significant limitations that have come about over the course of time and the importance of using new science and newer technology and newer estimates to be able to better estimate our kidney function for medication-related drug dosing.

00:06:09 Tracy Anderson-Haag

Another big issue is the weight that you choose to use for Cockcroft-Gault.

00:06:13 Tracy Anderson-Haag

Because it's not related to body surface area adjustment, you have to select whether you're going to use an actual body weight, an ideal body weight, a lean body weight, an adjusted body weight, a total body weight.

00:06:22 Tracy Anderson-Haag

And how that is applied is not consistent across pharmacy practice, even across two pharmacists within the same practice necessarily.

00:06:30 Tracy Anderson-Haag

And that can make a huge difference in your result when you have a weight, your weight on the numerator.

00:06:36 Tracy Anderson-Haag

And if somebody's using an ideal body weight of 50 kg,

00:06:39 Tracy Anderson-Haag

and the patient is actually 100 kilos, which is very possible, you are going to get twice the number for an EGFR, which probably has nothing to do with their actual kidney function.

00:06:50 Tracy Anderson-Haag

There are still some practices that artificially inflate that serum creatinine number if it's lower than a certain threshold.

00:06:56 Tracy Anderson-Haag

That used to be one when I first started practicing when we had the old non-standardized creatinine.

00:07:02 Tracy Anderson-Haag

And now oftentimes if it's less than 0.8, there'll be rounding that takes place and there's no scientific basis for that and it's not applied consistently across practices either.

00:07:11 Tracy Anderson-Haag

And so I think the variability that you can get with Cockcroft-Gault is grossly expanded compared to what you see with newer eGFR equations that are

00:07:20 Tracy Anderson-Haag

body surface area BSA adjusted using a total body weight and actual patient size, a weight and height at the current time or very recently.

00:07:30 Tracy Anderson-Haag

And so I think that also makes the variability of the answers that you're going to get between two different pharmacists with Cockcroft-Gault much different than you should be getting the exact same number if you're using an eGFR estimator BSA adjusted.

00:07:44 Steve Small

Great. And I feel this is a good spot to do a deeper dive into considerations about creatinine since it's used in our eGFR equations.

00:07:51 Steve Small

So what are some of creatinine's limitations for estimating kidney function?

00:07:57 Erin F. Barreto

Yeah, there's many.

00:07:59 Erin F. Barreto

So first, this is an endogenous substrate, meaning it has factors that affect it other than kidney function.

00:08:06 Erin F. Barreto

So it's the terminal byproduct of skeletal muscle catabolism.

00:08:09 Erin F. Barreto

So anything that affects skeletal muscle mass,

00:08:11 Erin F. Barreto

to grow skeletal muscle mass because you're bulking up in bodybuilding or more commonly in our sick patients to lose skeletal muscle mass through cachexia or inflammation or chronic disease.

00:08:22 Erin F. Barreto

You can alter your serum creatinine independent of your underlying kidney function.

00:08:26 Erin F. Barreto

But there are many other factors that can affect serum creatinine, including dietary intake, competing medications at the level of tubular secretion, unstable kidney function that changes the proportion of filtration in kidney and tubular secretion.

00:08:40 Erin F. Barreto

So there's many, many factors that affect Cockcroft-Gault that can make it hard to interpret when it comes to especially using it for drug dosing.

00:08:50 Tracy Anderson-Haag

Yeah, I think the biggest issue with Cockcroft-Gault, I agree with all you said, but serum creatinine is used in our newer estimating equations that we think are better as well.

00:08:59 Tracy Anderson-Haag

And so that limitation of the validity of serum creatinine is still a problem with any estimating equation that's using creatinine as a variable.

00:09:09 Tracy Anderson-Haag

And so Cockcroft-Gault also has creatinine, so it's impacted by that.

00:09:12 Tracy Anderson-Haag

But the fact that it hasn't been validated in a broad patient population and that it was studied and developed,

00:09:20 Tracy Anderson-Haag

in a time when serum creatinines were 12% higher than they are now, the answers that we're getting from that number are really not relevant in the current lab environment with the current serum creatinine that we're getting.

00:09:33 Tracy Anderson-Haag

And so I think just the inability to validate that in a broader population can limit it.

00:09:40 Steve Small

And with that in mind, why are new CKD-EPI equations recommended to estimate GFR?

00:09:45 Steve Small

What are their benefits here?

00:09:48 Tracy Anderson-Haag

So because our, so the NKF, several organizations have come out and said that we need to use race-free, race-agnostic estimating equations for both medication-related decision-making and staging of chronic kidney disease.

00:10:05 Tracy Anderson-Haag

And so they have given us three equations that meet those criteria and have been validated in the most broad and diverse patient population.

00:10:14 Tracy Anderson-Haag

And that would be the CKD-EPI 2021 creatinine based estimate, the CKD-EPI 2021 CKD-EPI creatinine cystatin C or the 2012.

00:10:27 Tracy Anderson-Haag

CKD-EPI cystatin C, which has never included a race variable.

00:10:31 Tracy Anderson-Haag

And so we have 3 equations to choose from that meet that race agnostic criteria.

00:10:36 Tracy Anderson-Haag

Those are going to generally be reported in medical records, and they are generally going to be reported in a standardized format of mL/min per 1.73 meters squared.

00:10:45 Tracy Anderson-Haag

And we know that very few people are 1.73 meters squared.

00:10:50 Tracy Anderson-Haag

I certainly am not at 5'0".

00:10:52 Tracy Anderson-Haag

And so we know that if somebody is 1.73 meters squared, that in fact is their GFR in mL/min.

00:10:59 Tracy Anderson-Haag

But if they're not, their GFR will be higher if they're larger than 1.73 and lower if they're lower than 1.73.

00:11:06 Tracy Anderson-Haag

And medications don't clear by standardized forms.

00:11:10 Tracy Anderson-Haag

They clear by body size.

00:11:11 Tracy Anderson-Haag

And so when we want to use these for medication related decision making, we're going to convert them into mL/min using a BSA adjustment.

00:11:20 Tracy Anderson-Haag

And so those equations have been shown.

00:11:24 Tracy Anderson-Haag

There have been pharmacokinetic studies that have demonstrated with several medications that are cleared primarily by the kidney with narrow therapeutic indexes that these equations outperform as far as accuracy and precision, Cockcroft-Gault or other previous iterations of these CKD-EPI or MDRD or other equations that have not been chosen as our most reliable equations.

00:11:48 Tracy Anderson-Haag

So we have more accurate measures and that generally is compared again to our gold standard of measured GFR.

00:11:55 Tracy Anderson-Haag

So these three equations, body surface area adjusted, are closer estimates with accuracy to measured GFR.

00:12:05 Steve Small

And as we talk about biomarkers, let's talk about Cystatin C, another biomarker we mentioned earlier.

00:12:11 Steve Small

Erin, can you tell us more about Cystatin C and how it's different from creatinine?

00:12:18 Erin F. Barreto

Sure. So cystatin C is a low molecular weight protein produced by all nucleated cells.

00:12:23 Erin F. Barreto

So it's a little bit different in its origin story than creatinine in the sense that it's not coming from muscle mass, as it were.

00:12:31 Erin F. Barreto

It is eliminated primarily by glomerular filtration, and then it's reabsorbed into the proximal convoluted tubule and catabolized.

00:12:37 Erin F. Barreto

So there isn't any systemic reabsorption, nor is there meaningful tubular secretion.

00:12:41 Erin F. Barreto

So that improves upon one of the known limitations of creatinine, which is the 15%-ish

00:12:47 Erin F. Barreto

tubular secretion that we tend to see with it leading to the GFR overestimation.

00:12:51 Erin F. Barreto

So cystatin C is not a new biomarker, but it might be new to some of the listeners.

00:12:55 Erin F. Barreto

So it kind of emerged on the scene for GFR analysis in the 80s.

00:13:01 Erin F. Barreto

But then in 2012, it made its splashy debut in the CKD guidelines as a confirmatory test for CKD.

00:13:08 Erin F. Barreto

And then since then, it's been heralded as a way to kind of further understand kidney health, particularly when creatinine is less accurate.

00:13:19 Erin F. Barreto

When we think about the key points about cystatin C that make it similar or different to creatinine, so it can be used for GFR assessment, but it also is biologically active.

00:13:29 Erin F. Barreto

And so there are factors other than kidney function that affect the serum concentration of cystatin C.

00:13:36 Erin F. Barreto

So we think of things that affect cell turnover, right?

00:13:38 Erin F. Barreto

Like I said, that this is related to nucleated cells.

00:13:41 Erin F. Barreto

So if you have somebody who has uncontrolled, rapidly proliferating malignancy and their cells are lysing and rapidly turning over, for example, lymphoma, brand new diagnosis of lymphoma, you're going to have a serum concentration of cystatin C that's going to be very high relative to what your actual underlying GFR would be.

00:14:00 Erin F. Barreto

And it would be not reflective of your GFR.

00:14:03 Erin F. Barreto

People with uncontrolled hyperthyroidism.

00:14:05 Erin F. Barreto

It also has a relationship to the inflammatory cascade, so things that cause widespread inflammation

00:14:11 Erin F. Barreto

for example, uncontrolled opportunistic infections would be a case, or AIDS, it would be a case where you really would have to worry that the cystatin C concentration might be very high, disproportionate to what your underlying true GFR is.

00:14:23 Erin F. Barreto

There's also a relationship with corticosteroid exposure, where exposure to corticosteroids, particularly high doses of corticosteroids, can lead to increases in cystatin C that have nothing to do with your kidney function.

00:14:36 Erin F. Barreto

It's not that you can't use it in those circumstances.

00:14:38 Erin F. Barreto

And in fact, especially if you combine it with creatinine in the combined equation that Dr. Anderson-Haag mentioned, it still probably adds value relative to using either biomarker alone.

00:14:50 Erin F. Barreto

But you do need to have an understanding of those issues when you contextualize.

00:14:54 Erin F. Barreto

Obesity, for example, is another factor.

00:14:55 Erin F. Barreto

There's a higher concentration of cystatin C in adipose tissue.

00:14:59 Erin F. Barreto

And so that independently can increase it.

00:15:02 Erin F. Barreto

The other thing to be aware of about cystatin C, so when we think about creatinine, one of the things that we think about is the lag.

00:15:08 Erin F. Barreto

So if you have a patient who has acute kidney injury or short-term kidney dysfunction over hours to days, which I know isn't the huge focus for today's presentation, but we do need to acknowledge it.

00:15:18 Erin F. Barreto

If you have a patient who has acute kidney injury, creatinine is like looking through the rear view mirror.

00:15:22 Erin F. Barreto

in that, usually it has a 24 to 48 hour lag from the onset of kidney damage.

00:15:28 Erin F. Barreto

So by the time you see the creatinine rise, you're already way behind the eight ball when it comes to trying to make drug decisions.

00:15:37 Erin F. Barreto

So cystatin C also has a lag, but it's not quite to the same degree.

00:15:41 Erin F. Barreto

So we think usually more on the 12 to 24 hour side when it comes to the kinetics of it, both on the onset of acute kidney injury and during the recovery.

00:15:50 Erin F. Barreto

And so it might have a little bit more favorability in that respect.

00:15:54 Erin F. Barreto

Dr. Anderson-Haag had drawn out the three CKD-EPI equations that have been developed to be race agnostic and really heralded as the ones that we should be choosing.

00:16:04 Erin F. Barreto

When we look at the performance data of those for measured GFR, not talking about drug dosing, what has been shown is that the combined equation with creatinine and cystatin C together has more accurate and more precise than either the eGFR creatinine or the eGFR cystatin C for prediction of measured GFR.

00:16:26 Erin F. Barreto

And that's not the same thing as trying to predict drug clearance.

00:16:31 Erin F. Barreto

That's a different outcome entirely.

00:16:33 Erin F. Barreto

But nevertheless, I think what we can say is that the combined equation at a population level is the most accurate for prediction of measured GFR.

00:16:41 Erin F. Barreto

That doesn't mean for your patient in front of you, that's the right choice, but at a population level, that is.

00:16:47 Erin F. Barreto

because it balances these non-renal factors, these non-kidney factors that affect the activity of either of these biomarkers and then kind of puts them all into one big soup together and tries to balance them out.

00:16:59 Erin F. Barreto

So it would be inaccurate to say that eGFR cystatin C is more accurate, consistently more accurate than eGFR creatinine.

00:17:06 Erin F. Barreto

That's not true. That's not evidence-based.

00:17:08 Erin F. Barreto

What can be said is that the combined equation is really where it is at at the population level.

00:17:14 Steve Small

Now, in practice, though, how do you pick which equation to use?

00:17:18 Steve Small

Are there any rules of thumb our audience should be thinking about, if there are any at all?

00:17:24 Erin F. Barreto

We're talking about this in general at the population level, and we're assuming that you don't have cystatin C available to you, which statistically speaking, the majority of places right now don't have it available to them or routinized in their practice.

00:17:38 Erin F. Barreto

The majority of people are going to have eGFR creatinine.

00:17:41 Erin F. Barreto

And so the best available choice for eGFR creatinine right now on average and is recommended is the 2021 eGFR creatinine based on CKD-EPI.

00:17:53 Erin F. Barreto

However, I think we will get to this at some point when we transfer that from CKD diagnosis, which probably isn't the main focus of your audience,

00:18:04 Erin F. Barreto

to drug dosing, it is important to include the individualized BSA into it so that it is not expressed in the native unit, which is mL/min per 1.73 meters squared, but rather expressed in mL/min, which would be more suitable for drug dosing.

00:18:20 Erin F. Barreto

So that I think is kind of the general answer.

00:18:23 Erin F. Barreto

If you have both creatinine and cystatin C available to you, then I think it's a bit of a debate as to which one you use, and it really depends on your patient factors.

00:18:35 Tracy Anderson-Haag

I agree completely that generally speaking, the vast majority of the time you're going to be using CKD-EPI 2021 creatinine body surface area adjusted.

00:18:47 Tracy Anderson-Haag

But, if there's generally a reason you're getting a cystatin C, if you're getting a cystatin C, and then depending on your patient factors, the combined equation oftentimes can make up the difference of limitations from both of those factors and be the most accurate.

00:19:02 Tracy Anderson-Haag

But in certain patient situations, I always say garbage in, garbage out.

00:19:07 Tracy Anderson-Haag

If you know your creatinine is severely limited because your patient has no muscle mass, they're completely wasted.

00:19:13 Tracy Anderson-Haag

Any equation that contains creatinine is going to be negatively impacted as far as accuracy.

00:19:18 Tracy Anderson-Haag

So in that case, the cystatin C alone may be the best estimate.

00:19:23 Tracy Anderson-Haag

Same thing if you have somebody that's extremely obese, your cystatin C is going to be significantly impacted.

00:19:29 Tracy Anderson-Haag

Any equation that contains cystatin C may also not be accurate.

00:19:33 Tracy Anderson-Haag

That said, in many stages of obesity, not severe, severe obesity, but class 1, 2, and 3 obesity, the combined equation, even with that limitation of cystatin C outperforms either of the other equations.

00:19:46 Tracy Anderson-Haag

And so I think it just population-wise, if you're thinking about the number of kidney function estimates that are done by pharmacists in the United States today, I would be willing to guess even 95% or more would be a creatinine-based estimate.

00:20:01 Tracy Anderson-Haag

We hope that would shift from Cockcroft-Gault to eGFR measures.

00:20:06 Tracy Anderson-Haag

Very few people have implemented cystatin C, and I think it's very unique situations where we're able to access cystatin C.

00:20:12 Tracy Anderson-Haag

I think that will change over time.

00:20:15 Tracy Anderson-Haag

But if you're having to select between equations for a certain patient, it really depends on what the factors are of that patient and why you're deciding to look at a cystatin C in the 1st place.

00:20:27 Erin F. Barreto

I would just add that when it comes to the combined equation for the audience, I would just indicate that

00:20:36 Erin F. Barreto

it is not mathematically exactly right.

00:20:38 Erin F. Barreto

You can think of it kind of as an average of the two.

00:20:41 Erin F. Barreto

It's not an arithmetic average, but it's kind of an average of the eGFR creatinine and the eGFR cystatin C.

00:20:47 Erin F. Barreto

So let's say you have a patient, as was pointed out, who has terrible muscular dystrophy and their creatinine is that one that never goes above 0.6.

00:20:56 Erin F. Barreto

The best available creatinine that they've got is 0.6.

00:20:59 Erin F. Barreto

And when their kidneys are torched, it's still 0.6.

00:21:03 Erin F. Barreto

In those cases, if you use the combined equation, that overestimated GFR from the creatinine is just going to draw up the GFR.

00:21:11 Erin F. Barreto

It's just going to draw the average-ish up and it's going to make it look better than it is.

00:21:16 Erin F. Barreto

That's I think why Tracy is pointing out that in those cases, those were circumstances that you would probably want to use the single biomarker equation with cystatin C.

00:21:26 Erin F. Barreto

I also would just like to point out a practical point here, which is like in the electronic health record environment that most of us have available to us, if you have one available in your environment at all to use.

00:21:39 Erin F. Barreto

Most of the time, it's important for us to kind of keep it simple.

00:21:43 Erin F. Barreto

We can't be showing people 10 different equations without context or reason and expecting them to parse, oh, I should use this one in this circumstance and this one in this circumstance and this one in this circumstance.

00:21:55 Erin F. Barreto

It's too difficult.

00:21:57 Erin F. Barreto

And obviously our EHRs are getting smarter and so they could in some contexts.

00:22:01 Erin F. Barreto

restrict or show things strategically.

00:22:05 Erin F. Barreto

But in general, you kind of have to pick one for everybody that is broadly available.

00:22:11 Erin F. Barreto

And what's broadly available is probably going to be the eGFR creatinine.

00:22:15 Erin F. Barreto

And when you have that, you probably want to use the contemporary equation and you probably want to make sure that the unit of measure that is used is context appropriate.

00:22:25 Steve Small

I'm glad we're bringing up this BSA adjusted for dosing to get the mL/min units, which is key for drug dosing.

00:22:31 Steve Small

When should I not adjust for body surface area?

00:22:34 Steve Small

Are there any circumstances, albeit rare, where that would come into play?

00:22:38 Steve Small

Or should pharmacists only be dealing with mL/min units based on these equations?

00:22:45 Tracy Anderson-Haag

If your patient is 1.73 meters squared, you do not have to adjust for body surface area.

00:22:52 Tracy Anderson-Haag

If they are not 1.73 meters squared, you should be adjusting for body surface area.

00:22:57 Tracy Anderson-Haag

I say that a little bit facetiously.

00:22:59 Tracy Anderson-Haag

If they're close to that, the difference in that adjustment is not going to be huge.

00:23:05 Tracy Anderson-Haag

So obviously the bigger impact of this is going to be people at extremes of weight or size.

00:23:11 Tracy Anderson-Haag

And so if you're limited in your time and you can only do so many calculations a day or your EHR is not able to do those calculations for you, you're going to get the most return on investment for those folks that are farthest away from their ideal body weight or their normal body size if they're like 1.73 meters squared.

00:23:31 Tracy Anderson-Haag

1.73 meters squared is not the average size of an American today.

00:23:35 Tracy Anderson-Haag

I think it's over 2 for men and about 1.8 something for women in the current era.

00:23:42 Tracy Anderson-Haag

And so generally speaking, it's going to need to happen for everyone.

00:23:46 Tracy Anderson-Haag

And really, if you're thinking about drug dosing, that should be in mL/min.

00:23:49 Tracy Anderson-Haag

We filter in mL/min, we clear in mL/min.

00:23:51 Tracy Anderson-Haag

Our kidney does not standardize for 1.73 meters squared.

00:23:58 Steve Small

And this is a good time to point out that to make calculations easier, there are online calculators available to you for these equations.

00:24:06 Steve Small

because these calculations are complex.

00:24:09 Steve Small

I personally wouldn't attempt to do the CKD-EPI equations by hand, and there are online calculators available where you can enter the patient factors such as creatinine and cystatin C labs, age, sex, and it will generate the answer for you.

00:24:24 Steve Small

And some of these calculators, such as the National Kidney Foundation version, can perform the BSA adjustment for you as well if you enter a height and weight.

00:24:33 Steve Small

But be sure to double check that the calculator you're using can do BSA adjustment before using the result for any medication-related decisions.

00:24:42 Steve Small

And if it doesn't, be prepared to do the BSA adjustment manually.

00:24:46 Steve Small

But I'm thinking here with the calculator options we have, is there anything else we should be thinking about?

00:24:53 Tracy Anderson-Haag

And I think a nice thing about the online calculators, and Erin had mentioned this too, is that usually you're going to have a creatinine and a cystatin C-based answer if you have both of those pieces of information.

00:25:04 Tracy Anderson-Haag

And then somewhere in the middle will be the combined equation.

00:25:06 Tracy Anderson-Haag

And whether or not it's higher or lower depends on what your cystatin C and creatinine are.

00:25:11 Tracy Anderson-Haag

But that will give you, if you have all of those numbers, it gives you a range.

00:25:15 Tracy Anderson-Haag

It gives you a range, sort of like my worst case scenario would be here, my best case scenario would be here, and sometimes that's the best we can do.

00:25:23 Tracy Anderson-Haag

And so I really like that those calculators, if you do have both of the variables of creatinine and cystatin C, provide all three of those answers body surface adjusted for you and can kind of give you that idea and range.

00:25:34 Tracy Anderson-Haag

And you could go ahead and also estimate a Cockcroft-Gault and see where that helps you land in the middle of this thing and somehow get at least a confident idea of 20 to 40 or 40 to 60 to find that dosing window for the medication you're working with, that clinical application.

00:25:53 Erin F. Barreto

90% of the drug dose choices you're going to make are going to be the same because of the point that was raised, which is we're not trying to dial in 2 mils per minute for making medication decisions.

00:26:04 Erin F. Barreto

We're trying to dial in a category, which is 20, 30, 40 mL/min wide.

00:26:10 Erin F. Barreto

I think perfection sometimes in this is the enemy of good.

00:26:13 Erin F. Barreto

I think in general, make the move to eGFR creatinine.

00:26:17 Erin F. Barreto

Most of your decisions are not going to be affected.

00:26:19 Erin F. Barreto

And those that are probably going to get better and more accurate with this change.

00:26:25 Sara Klockars

And how to handle medications where the labeling or like the drug reference states Cockcroft-Gault.

00:26:32 Sara Klockars

Can you just make the jump and just use the eGFR that the EHR is calculating?

00:26:39 Tracy Anderson-Haag

So the NKF work group that was representative of a very broad population of people, not just pharmacists, but all healthcare providers were represented.

00:26:50 Tracy Anderson-Haag

Compendia, the FDA, everyone, when you think about how poorly Cockcroft-Gault is actually estimating GFR, remember it's a creatinine clearance estimate, when you think about how poorly that is actually estimating GFR, and we have blindly continued to use that for 50 years, I think that it is not much of an ask to go ahead and shift over.

00:27:16 Tracy Anderson-Haag

When we have good data, there's very good published data on four narrow therapeutic index

00:27:22 Tracy Anderson-Haag

that are cleared renally that would tell us that the eGFR is calculated by CKD-EPI, the three acceptable race agnostic equations, better mirror or more accurately estimate GFR.

00:27:38 Tracy Anderson-Haag

And so we are not going to ever see drug companies redo these studies using eGFR.

00:27:48 Tracy Anderson-Haag

And so we have to start somewhere.

00:27:50 Tracy Anderson-Haag

It can't be worse than what we've been doing with Cockcroft-Gault for the last, well, at least since creatinine was standardized, which was, you know, mid 2000, 2005, at least by 2011.

00:28:04 Tracy Anderson-Haag

And so we've had 15 years of using Cockcroft-Gault with serum creatinines that were 12% lower on average and blindly went through that.

00:28:13 Tracy Anderson-Haag

And so the recommendation is that we go ahead and utilize those nomograms that are put in Compendia, whether they were developed through Cockcroft-Gault or MDRD.

00:28:24 Tracy Anderson-Haag

or CKD-EPI that used race or CKD-EPI that was race-based, whether they're reported in mL/min or mL/min per 1.73 meters squared, we should be using a BSA adjusted mL/min result and utilizing those same tables.

00:28:41 Tracy Anderson-Haag

Although we do not feel more research is needed to be able to support that practice, we certainly would welcome people being able to compare what they're getting with measured GFRs, especially with medications that we can do therapeutic drug monitoring to continue to show that the choices that we're making are correct.

00:28:59 Tracy Anderson-Haag

And as we've mentioned before, a lot of this has to also do with clinical management of the patient.

00:29:04 Tracy Anderson-Haag

You're getting these numbers, you're looking at these tables, but you have to think about the calculation that

00:29:10 Tracy Anderson-Haag

getting, how confident you are in that estimate, and what is the best for the patient if you're going to sort of round up or round down in your dosing choices, what are the pros and cons of those things?

00:29:22 Tracy Anderson-Haag

So there is never going to be a way that you can just black and white this and look at a chart and make good dosing decisions with any estimate you have.

00:29:31 Tracy Anderson-Haag

You're always going to have to think about that result and think about how you're applying it.

00:29:37 Sara Klockars 

How should we approach drug dosing in patients on dialysis?

00:29:41 Sara Klockars

Do these equations still apply, Tracy?

00:29:46 Tracy Anderson-Haag

No, they do not.

00:29:47 Tracy Anderson-Haag

So these equations are estimating your kidney function, how your kidney is clearing medications.

00:29:54 Tracy Anderson-Haag

And when we have dialysis therapy, whether that's peritoneal dialysis, hemodialysis, continuous dialysis, we have a machine that is removing our biomarker, that is lowering our creatinine, that is impacting our cystatin C.

00:30:08 Tracy Anderson-Haag

And so we cannot estimate kidney function using estimating equations if you've had dialysis.

00:30:15 Tracy Anderson-Haag

If you're on chronic dialysis, generally we would say your eGFR is less than 10.

00:30:20 Tracy Anderson-Haag

And most compendia would have a less than 10 section or a specifically hemodialysis section or a peritoneal dialysis section, continuous dialysis section.

00:30:29 Tracy Anderson-Haag

And so you're going to dose based on that.

00:30:31 Tracy Anderson-Haag

And you may need to be dosing depending on what their dialysis schedule is, depending on kinetics of different medications.

00:30:38 Tracy Anderson-Haag

If you have somebody that's having intermittent dialysis, again, that's probably an acute kidney injury situation versus a chronic kidney disease situation.

00:30:47 Tracy Anderson-Haag

And these estimating equations are assuming a stable creatinine or a stable cystatin C, a stable level of kidney function and chronic disease.

00:30:58 Tracy Anderson-Haag

And so these equations are not perfect in that setting.

00:31:02 Tracy Anderson-Haag

Do we use them? Sometimes, but you also have to be thinking about what you're putting in and what's coming out and how accurate that is.

00:31:09 Tracy Anderson-Haag

If you have a creatinine that's actively falling, you're probably going to be underestimating someone's function if you're using this.

00:31:15 Tracy Anderson-Haag

If you have a creatinine that's actively rising or no urine output, that's telling you what their kidney function is right there.

00:31:21 Tracy Anderson-Haag

So again, that clinical scenario.

00:31:22 Tracy Anderson-Haag

But generally speaking, if someone is using a dialysis machine at some point or has in the recent days, you would not be using these estimating equations.

00:31:31 Tracy Anderson-Haag

And anyone on chronic dialysis therapy, you would estimate their GFR as less than 10.

00:31:37 Tracy Anderson-Haag

There are some nuances with residual renal function.

00:31:39 Tracy Anderson-Haag

You still cannot use these estimations and safely less than 10 is an appropriate estimate for you.

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