Assessing Kidney Function: Glomerular Filtration Rate (GFR) with Case

00:01 We've just talked about defining chronic kidney disease.

00:04 But how do we assess kidney function? There's a couple of different ways that we can do that in order to get an estimate of what our GFR is or glomerular filtration rate.

00:13 One of these is looking just at serum creatinine.

00:16 So serum creatinine is derived from the metabolism of creatine in skeletal muscle and from dietary meat intake.

00:23 It's released into the circulation at a constant rate.

00:26 So we'll have a stable plasma concentration.

00:29 It's freely filtered across the glomerulus and it's neither reabsorbed nor metabolized that's important because we can use that to assess kidney function.

00:38 However, you have to keep in mind.

00:40 It's inversely proportional to the GFR meaning that if I have a very high creatinine my GFR is quite low.

00:48 And a little caveat we can only use this with stable kidney function.

00:52 We can't use this with things like acute kidney injury.

00:56 So some of the other limitations with using creatine as a GFR measurement is that it's not accurate in patients with little muscle mass.

01:05 We just said that this is based on creatine from skeletal muscle.

01:09 So in patients who have things like liver disease where they're very malnourished or other malnourished states or perhaps somebody who has congenital dwarfism where they have very little muscle mass that definitely will impact their creatinine and give them a lower creatinine.

01:23 So that won't necessarily correlate with their renal function.

01:28 Another thing to think about is that creatinine is also secreted by the organic secretory pathway in the proximal tubule.

01:35 Now that becomes important because there are certain medications that can inhibit the secretion of creatinine and therefore increased that serum creatinine despite no change in GFR.

01:46 An example would be trimethoprim or cimetidine these drugs bind to that organic secretory pathway.

01:52 They will inhibit the secretion of creatinine, therefore you have an elevation in the serum, but renal function is the same so it's not accurate and that's the circumstance.

02:01 And finally one of the biggest issues with using serum creatinine is it doesn't detect early changes in GFR and that's important because you really want to target that population who's really at the initial cusp of having chronic kidney disease.

02:15 So again, I'm going to underscore that an initial small rise in serum creatinine will reflect a market change in GFR.

02:23 And it's interesting because a market rise in serum creatinine with advanced disease actually reflects only a small absolute reduction in GFR.

02:32 Here's a graphical representation that's illustrating my point.

02:35 If you see on the y-axis serum creatinine is located there in milligrams per deciliter and on the x-axis, it's GFR in mils per minute.

02:45 So for example, if I have a patient who has a serum creatinine of 0.7 that then increases to 1.1 milligrams per deciliter.

02:53 It can reflect nearly a 40 mil per minute loss in GFR.

02:58 Whereas a serum creatinine that increases from four milligrams per deciliter to 5 milligrams per deciliter may only reflect a loss of four to five mils per minute.

03:07 So it really makes creatinine as a biomarker for renal function a difficult one to use.

03:14 So what else do we have in our armamentarium to look at renal function? How about creatinine clearance? So clearance is really the rate at which a substance is removed or cleared from the body by the kidneys.

03:26 So we use our formula UV/P where U is going to stand for our urinary concentration of a substance in this case creatinine.

03:35 V is our volume of urine percept period of time in most circumstances will use 24 hours and P is the plasma concentration of a substance.

03:44 This is going to be creatinine.

03:46 So because creatinine is filtered and not reabsorbed by the tubule, we can really use that as a measurement for the clearance of creatinine in order to obtain the measurement of GFR.

03:59 But once again, there are limitations that we have to consider.

04:03 Now remember we just talked about a few slides ago that creatinine is also secreted into the tubule by that organic secretory pathway.

04:11 So the urinary creatinine concentration will actually be higher than what's actually filtered.

04:16 So therefore using a creatinine clearance.

04:19 It's going to overestimate or exceed the true GFR maybe by about twenty, ten to twenty percent.

04:26 The other problem is that if any of you have ever had to do a 24-hour urine collection, you will understand that it's very difficult for patients to do.

04:35 They notoriously will either over or under collect and it's actually quite an undertaking.

04:40 People have to store their urine in the refrigerator.

04:43 They oftentimes have to be at home so they can't be at work during this time period, So it's just not feasible to do all of the time.

04:51 So because of those limitations that I've outlined above creatinine clearance really is no longer the recommended is no longer routinely recommended for assessing GFR.

05:02 Okay, so that brings us to one of our newer advents, which is the modifications of diet and renal disease estimated GFR or eGFR, the MDRD equation.

05:11 You probably have heard of this quite a bit if you're in the clinical working environment.

05:16 So this is a formula that estimates GFR by incorporating known demographic and clinical variables as observed surrogates for these unmeasured factors other than GFR that affect our serum creatinine.

05:29 So this was actually based on a cohort of patients that were follow prospectively over time and that they found that by using things like age, gender, ethnicity and creatinine and they plug this into a very complicated and difficult equation, of course, which you are not responsible for because most of us have calculators that will determine this for us, but it allows us to obtain the estimated GFR in our patients.

05:59 So it's nice because it it's used not only to estimate GFR but this is how you can follow your patients over time to see how their GFR is changing.

06:09 Now one caveat about the MDRD is it does become less accurate when GFR is greater than 60 mils per minute.

06:17 So we do have another estimated GFR equation called the ckd-epi formula.

06:23 This is the chronic kidney disease epidemiology collaboration equation.

06:26 And again, this was based on a cohort of patients that were followed longitudinally over time.

06:33 And what's nice about this particular formula is that it was really developed in order to gain a more accurate estimation of GFR when that GFR is greater than 60 miles per minute.

06:44 So again, it also is going to estimate GFR on these observed surrogates which include age, gender, ethnicity and creatinine.

06:54 And again, what's nice is that allows us better accuracy than the MDRD when that GFR exceeds 60 mils per minute.

07:04 So I think what's most important when you're taking care of patients clinically is you'll need to know which method your institution will use.

07:12 Most institutions will actually discuss whether or not they're using MDRD or the ckd-epi, but if you want a more accurate estimation of GFR when it exceeds 60 mils per minute, it'll be important to use the ckd-epi equation.

07:26 Okay.

07:27 So let's go to a clinical case.

07:30 We have an 82 year old woman who weighs 48 kilos and she has a creatinine of 1.2 milligrams per deciliter.

07:39 Now her 26 year old grandson who competes in bodybuilding competitions weighs 90 kilos and he is all muscle and has a creatinine of 1.2 two milligrams per deciliter.

07:50 So the question is do they have the same renal function? Let's see if we have some clues that can help answer this question.

07:59 So we've got a woman who is relatively advanced age.

08:03 She is 82 and look at how much she weighs.

08:06 She's half the amount that her grandson ways.

08:10 So her muscle mass is less and that's important because remember part of this, part of renal function is really going to be based on creatinine and creatinine is coming from muscle mass.

08:22 So the answer is no.

08:24 This really underscores the importance of using estimated GFR equations that are based on not only creatinine but these other demographic variables that we were discussing in those last two estimated GFR equations.

08:38 So this is a table that really illustrates what I'm talking about.

08:41 So just using serum creatinine versus using eGFR.

08:46 So if you look at the top we're looking at people's age their gender, their race, their serum creatinine, and their estimated GFR.

08:55 So if we have a 20 year old gentleman who is African-American and his serum creatinine is 1.3.

09:02 His estimated GFR is about 91 mils per minute.

09:06 Now, let's take that same age same gender, but now this is a Caucasian gentleman.

09:11 Same creatinine.

09:12 Look at how the GFR changes its now 75 mils per minute.

09:16 Why is that? Because traditionally Caucasian ethnicities have less muscle mass than African people of African descent.

09:25 Now we take the same exact factors, but now we're changing the gender to being female.

09:31 We have that creatinine of 1.3.

09:34 The estimated GFR is now 56 mils per minute quite a big difference because females traditionally have less muscle mass than males.

09:43 Now what happens if I now manipulate the age I have somebody now that's older.

09:49 So they're at 50 same other factors.

09:52 So still a female who is Caucasian with a creatine of 1.3 that GFR now drops by 10 mils per minute.

09:58 It's now 46 mils per minute.

10:00 Now I'm going to change my race again.

10:03 So if I have an African-American woman who is 50 years old with a serum creatinine of 1.3.

10:08 You can see that that GFR goes up to 56 miles per minute and finally manipulating that age up to 70 you can see that that GFR drops to 43 miles per minute.

10:19 So this is how you can see that using serum creatinine alone is simply inadequate to really assess renal function and is estimated GFR is although not perfect really give us a much better idea of how our patients renal function actually is doing.

10:35 So we've just talked a lot about measuring GFR.

10:39 Why is it important? So there's a couple of things that I really want you to keep in mind.

10:43 Number one.

10:44 We need a measurement of GFR because we want to evaluate patients who actually have kidney disorders and we just talked about how the definition of chronic kidney disease, one of them is a decrease in GFR over time.

10:55 So that's very important.

10:57 Another very important point is that knowing GFR is really critical in order to appropriately dose medications that are cleared by the kidney.

11:07 If I give somebody a medication that's metabolized by the kidney and I don't dose it for the renal function.

11:13 They can have toxic levels accumulate and cause further damage.

11:18 It can also help us to avoid medications and nephrotoxic exposures that are going to harm the kidney.

11:24 We talked about in the acute kidney injury lecture that using iodinated contrast in patients who have underlying chronic kidney disease can really put them In harms way.

11:34 And finally, it's very helpful to stage people who have chronic kidney disease and having this estimated GFR allows us to do that and we do that so that we can target a population at risk.