Hello and welcome to the next lecture
in your nephrology curriculum.
Today, we're gonna be talking
about acute kidney injury
which is very near and dear to my heart as a
nephrologist because it's something that I see everyday
And it's something that you're going to encounter in
your professional life as you take care of patients.
So acute kidney injury is defined by
the abrupt loss of kidney function,
retention of urea and other
nitrogenous waste products
as well as the dysregulation of
extracellular volume and electrolytes.
Before we move on though, there's some important
terms that I really want you to understand
so you can better understand the cases
that we're going to be talking about.
The first is creatinine.
Creatinine is a breakdown product
of creatine phosphate in muscle.
It's filtered completely by the
kidney and it's not metabolized
and therefore is used to estimate
kidney function and filtration.
It does have an inverse
relationship to function meaning that
the higher the creatinine is, the
lower the GFR or filtration rate is.
You will also hear the word
BUN or blood urea nitrogen.
So urea nitrogen is formed from the
protein catabolism by the liver.
It's filtered by the kidneys and it's used
as an additional measure of kidney function.
Although a high BUN generally reflects lower
filtration, there's some caveats when it comes to BUN
and it can increase independently
of kidney function.
This includes things like glucocorticoids or
steroids when our patients are on steroids,
tetracycline antibiotics or reabsorption
of blood from the GI tract.
In each of those instances, the BUN may rise and the
creatinine might be normal as well as kidney function.
So do keep that in mind as
we're talking about BUN.
Oliguria is another
important term to know.
Our patients are commonly oliguric
when they develop acute kidney injury
and this really means that our
patients are producing less urine.
Typically, it's defined as less than 500 ml
of urine output within the 24 hours
but do keep in mind there are a few
definitions that will define oliguria
as less than 400 ml in the
24-hour period of time.
Finally, there's anuria.
Anuria is defined by less than 100 ml of
urine output in the 24-hour period of time
and this is essentially one of the
worst signs of of acute kidney injury
because our patients are essentially
not producing any urine.
If you remember nothing else from this lecture, do
remember that acute kidney injury is significant.
In our critically ill
patients who develop AKI,
their mortality is increased
between 40 to 60% at 60 days
and their hospital stay is prolonged.
Part of the reason why it's been so difficult
in order to care for and treat these patients
is because it took forever to develop
criteria in order to define what AKI is
and to stage AKI in order to develop
therapeutic targets in this population.
So finally, in the early part of the 2000's, the acute
kidney injury network came up with staging criteria
and this is based on absolute creatinine, a change
in serum creatinine, and reduction in urine output.
So beginning on stage 1, this includes a
creatinine increase of greater than 0.3 mg/dL.
That's really significant
because of the fact that
if you think about a patient whose creatinine
goes to 0.7 (mg/dL) to just 1.0 (mg/dL)
that means that that
patient has developed AKI
and when you look at that particular
patient, their mortality is increased.
We also look at the urine criteria as well, so less
than 0.5 ml/kg/hr over a 6-hour period of time.
Stage 2 is an increase in creatinine
of 2 to 3 times normal and then again,
a reduction in urine output over
the 12-hour period of time.
And finally stage 3, where patient's serum
creatinine is increased 3 to 4 times that of normal
or a serum creatinine greater than 4 mg/dL with
at least an acute increase of at least 0.5 mg/dL
and these patients oftentimes are anuric.
The higher the stage, the worse the outcome.
So, it's great that we have a staging system however
there are some caveats that we need to think of.
So despite having the consensus
for defining and grading AKI,
it still is based on serum creatinine and urine
output, and these two are really imperfect biomarkers
And again, if I'm talking about a biomarker, I'm
talking about a biological marker for organ injury.
Why is this?
Because when the serum creatinine
rises or urine output decreases,
already substantial injury has
taken place to that patient.
It diminishes, if you think about
that, the ability to begin treatments
aimed at preventing
the loss of renal function.
In the low, we have had
development of novel biomarkers.
There's things like NGAL,
kidney injury molecule 1, or NAG,
they're not ready for prime time yet and we're not
using them commercially in the US at this time.
So, let's kind of think about this
in a more conceptual fashion.
If we have a patient that's coming in, but there's
something about that patient during his hospitalization
that increases their risk for acute kidney
injury, that makes them susceptible.
It might be because they
have advanced stage.
They might be hypovolemic, they might have
diabetes mellitus, or they might be on medications
like non-steroidal anti-inflammatory
drugs which impair autoregulation.
An insult occurs to that patient
that creates acute kidney injury
and this is where we should be looking at our
biomarkers to detect that something's happened.
But instead, what happens?
it actually takes a substantial
amount of time for GFR to decrease
and our patients really aren't manifesting to us as
being injured until they already have kidney failure.
So it's really when they have complications of their
chronic kidney disease are they coming to our attention.
And you can see now how having
creatinine and urine output as biomarkers
are just inadequate when it comes to
defining when kidney injury happens
so that we can actually develop therapeutic targets
to help our patients at the time that they need it
rather than just taking care
of complications from their AKI.
So, let's move on to thinking about the etiologies
of different types of acute kidney injuries
and I think from our first
year of medical school,
everybody could really think about the 3 main
categories that you've been taught since day 1.
Which are really pre-renal, this includes things like volume
depletion and a decrease in effective arterial blood volume.
Intrinsic renal disease, and then this
is separated or I'd like to separate them
by different compartments of the kidneys.
This includes the tubules and interstitium.
That includes acute tubular necrosis, acute
interstitial nephritis, acute tubular obstruction,
the vascular compartments
so any kind of vascular disease
and of course my very favorite
which is glomerular disease.
And then finally, the post-renal category
which means that there's urinary obstruction
anywhere from the
renal pelvis to the urethra.