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.