Renal Clearance – Elimination Kinetics

00:01 Welcome to pharmacology by Lecturio.

00:03 Today, we're gonna talk about a topic that's really important when we're prescribing drugs and that's the concept of renal clearance.

00:11 Now, renal clearance is calculated with a formula that takes the rate of excretion in the urine divided by the plasma concentration.

00:21 When we have any kind of a drug that is polar and tends to be, excreted in the urine, we need to know what the renal clearance of that drug is so that we can figure out how often we dose it and what kind of doses that we use.

00:33 The kidneys are the main drivers of this process.

00:38 They filter out blood to the tune of 180 liters a day and they excrete urine through the ureters.

00:46 They collect in the bladder where it is held until it's appropriate to release.

00:52 Now, this is an important consideration because if you have a drug that's very highly renally excreted and you wanna treat something in the bladder, it's important that we use those drugs that are appropriate for that.

01:05 If, on the other hand, you have kidney failure, you wanna be very careful with drugs that are renally excreted.

01:11 Now, how do we calculate renal excretion? Well, let's start first with the Cockroft-Gault Formula.

01:19 Donald Cockroft and Professor Gault were a resident and professor combination who came up with this original calculation.

01:29 Now, there is a conversion factor that we use for US units and there's another conversion factor that we use if the patient is female, and you can see that here. Now, we don't really use this formula anymore.

01:43 The Cockroft-Gault formula may falsely lead to higher drug doses.

01:50 So, we don't use this.

01:51 Now, what we use is something called the 2021 chronic kidney disease epidemiology (CKD-EPI) creatinine equatio which gives you the estimated GFR or the eGFR.

02:02 This equation is recommended rather than other creatinine-based estimating equations such as the 2009 CKD-EPI equation, the Modification of Diet in Renal Disease (MDRD) study equation, or the Cockcroft-Gault equation.

02:17 Importantly, the 2021 CKD-EPI equation does not include a term for race, since the overall accuracy is reasonable for both Black and Non-Black groups.

02:29 Compared with the 2009 CKD-EPI creatinine equation, the 2021 equation slightly underestimates the estimated GFR in Black individuals and overestimates measured GFR in other individuals.

02:44 This race-neutral equation is recommended because using a Black race variable in eGFR could actually disadvantage Black patients with chronic kidney disease.

02:55 It could overestimate Black patients’ kidney function by as much as 16 percent.

03:01 It’s a problem to overestimate a patient’s kidney function because it means they could appear to be less sick on paper than they actually are, which could lead to poor management of chronic kidney disease and also make them wait longer to access waiting time for a kidney transplant —which starts when eGFR values are less than or equal to 20 mL/min.

03:22 And here is the calculation: Obviously, it's a much more difficult type of math to do but the nice thing is, is that we actually have the drug's--we actually have the patient's EGFR printed on the sheets when we get our lab results back just right under the creatinine value.

03:41 We do have a correction factors for males and females.

03:43 Now, all of these particular calculations are done post-blood work.

03:50 We don't do any of these estimations before blood work because we rely on the most recent creatinine and they can change.

03:57 Now, remember that we don't wanna use creatinine-based equations when patients have unstable creatinine concentrations.

04:04 An example of that in patients who are really muscular, a person who has a huge amount of muscle mass, say a bodybuilder, will have a very high creatinine value and therefore, their MDRD equation may falsely give you the idea that this patient has poor kidney function.

04:22 There are also changes in diet that can affect the creatinine concentration and therefore, the kidney--estimated kidney function.

04:29 Paraplegics and bodybuilders are the two categories of patients where you have to be particularly careful.

04:34 Paraplegics will have a low muscle mass, assuming that they have very little muscle mass in their legs.

04:40 Other diseases like muscle wasting diseases can alter your EGFR without actually having real world changes in your kidney function.

04:50 Vegetarians and people who are on low-meat diet may have low creatinines and give you a falsely elevated value.

04:57 People who are taking creatine dietary supplements may have changes in their creatinine levels because of it.

05:05 Finally, patients who are in the extremes of age, especially the elderly, are going to have altered creatinine-based equation values because of their advanced age.