00:01
So moving again in our tubular
interstitial disease process,
we're gonna be talking and
focusing on acute tubular obstruction
When our patients have acute tubular obstruction, it's
essentially precipitation of substances in the tubules
and there's a couple of different
categories that we really need to think about.
00:18
We can have protein from immunoglobulins,
this would be in the case of cast nephropathy
which we'll talk about in a minute.
00:25
This can be urate as in tumor lysis
syndrome just like our patient had.
00:30
We can have calcium phosphate
precipitate in the tubules
and that oftentimes can occur after receiving
a phosphorous-containing enema or laxative
And finally, giving medications can
cause intratubular crystal precipitations.
00:47
What's important is that when patient
develops intertubular obstruction,
it almost always occurs in the setting
of volume depletion and acidic urine.
00:56
So let's go over our first situation.
00:59
Our patient might develop acute tubular
obstruction from having cast nephropathy
This is going to typically occur when patients have plasma
cell dyscrasia or malignancies like multiple myeloma.
01:10
Remember in multiple myeloma, our patients essentially
have an overproduction of immunoglobulin light chains,
that are monoclonally restricted and so they're
produce in such a quantity that it burdens the kidney.
01:22
The kidney normally can reabsorb those
immunoglobulins in the proximal tubule
but they're so much and
there's such an incredible amount
that it actually starts to
glob up those tubules.
01:32
And again, combining that
with a Tamm-Horsfall protein,
then causes that to essentially
obstruct that outflow of urine.
01:41
We can also see acute tubular obstruction with
tumor lysis syndrome just like our patient had.
01:47
So this can occur following chemotherapy
where somebody has a very very high grade tumor,
And we can also see in this situation
that that tumor essentially liquefies,
we see this intracellular release of
uric acid, phosphate and potassium.
02:03
And that's what is most
indicative in our patient population.
02:08
Phosphorous-containing enemas are also a
problem and that actually wasn't discovered
until really probably around the
early part of the century around 2002.
02:17
So this includes a bowel
prep for colonoscopy.
02:22
So where we used to see this scenario is that our
patients will be undergoing potentially a sigmoidoscopy
and our gastroenterology colleagues might be giving
something like a sodium phosphorous enema or a laxative.
02:34
And in that setting of volume
depletion, they can precipitate
calcium phosphorous in
their tubules and interstitium.
02:41
Again, you can see that when that deposits,
it's associated with interstitial inflammation.
02:47
The highest risk is in our patients
with underlying chronic kidney disease.
02:52
And this is a very significant situation,
again you have to be a very good detective
but we have transplanted
patients over this situation.
03:00
So it's very important to be cognizant
of these phosphorous-containing enemas.
03:05
Medications are also important.
03:07
And then again, this is being a good detective
in understanding what your patients are getting
but we can see this with
intravenous acyclovir.
03:13
So a patient perhaps who's
coming in with HSV encephalitis,
with intravenous methotrexate which we
use in our chemotherapy armamentarium,
and things like sulfonamide antibiotics.
03:27
So, how do we diagnose our patients and how do
we work them up in order to clinch that diagnosis?
Once again, as we've been talking
about, we're gonna be good detectives
and we're really going to scour that chart, and
really take a very good history in our patients.
03:40
Sometimes, it's relatively easier if we know that our
patient perhaps has a history already of multiple myeloma.
03:47
We might be thinking about precipitation of those
immunoglobulin light chains causing cast nephropathy.
03:52
If our patient has a known malignancy and
they recently had chemotherapy administered,
then we think about things
like tumor-lysis syndrome
Have our patients recently used a fleet
enema or an oral sodium-phosphorous laxative?
That's also very important and what I
really want you to focus on as well is that
that really does take
good detective qualities.
04:14
So remember patients who are coming in
perhaps from a skilled nursing facility.
04:18
It's not uncommon for nursing facilities to automatically
place enemas on their patients in order to keep
from constipation and having issues like that.
04:29
And in that situation, those patients
absolutely can be administered
a fleet enema or a sodium-phosphorous enema
or laxative that can precipitate this phenomena.
04:39
So not just looking at their current
medications that they're receiving in the hospital
but really being that good detective in
talking to their nursing facility or other sources
where the patient may
receive this type of medication.
04:52
And then you want to do a
thorough medication review.
04:55
So looking at that medication
administration record - the AMR,
Have our patients received IV acyclovir?
Again, coming in with HSV encephalitis, that would
be a common scenario where we see this happen.
05:08
Do they have IV methotrexate for a
malignancy, or a sulfonamide antibiotics?
Laboratory evaluation can also be very helpful in
our diagnostic workup in clinching that diagnosis.
05:23
So for cast nephropathy, what we're really looking for are
those elevated free immunoglobulin light chains in the serum.
05:29
So specifically, we may want to order a serum protein
electrophoresis or SPEP with serum immunofixation.
05:37
We also can look at serum free
light chains and if these are elevated,
this can really lead us to the
diagnosis that perhaps cast nephropathy
is what's causing this
acute tubular obstruction.
05:48
For tumor lysis syndrome, we're
going to see things like high uric acid,
high phosphorous, high potassium levels just
as in the case of our patient at the beginning.
05:58
For phosphate nephropathy, we tend to see
very high phosphorouses and very low calciums.
06:03
Why is that?
Because remember what's happening, you have acute
calcium phosphate deposition in those tubules.
06:13
So for medications, what we oftentimes
can do is we can look at the urinary sediments
and we may see crystals from our precipitated
medications that can really lead us to that diagnosis.
06:27
So, what can we do to treat our patients
who have acute tubular obstruction?
So in cast nephropathy,
remember what's happening
and we have those immunoglobulin
light chains that are precipitating.
06:37
So we can actually administer
chemotherapeutic agents like
dexamethasone, proteasomal
inhibitor-based regimens
that are aimed at actually shutting
down that immunoglobulin production.
06:48
In cases of tumor lysis syndrome, we are really
going to aim at preventing that from happening.
06:54
So that means we are going to administer our chemotherapy
with high amounts of isotonic fluids like saline.
07:01
And uric acid lowering agents
like allopurinol and rasburicase
to prevent or shutdown production of uric
acid so that doesn't obstruct the tubules.
07:10
Acute phosphorous-nephropathy, unfortunately when we
give those phosphate-containing enemas or laxatives,
there's nothing we can do after that
situation other than offer supportive care.
07:20
But certainly there's something
that we can do at preventing that
and that's really just ensuring that our
patients never receive these types of medications
particularly our patients who have
underlying chronic kidney disease
because they are the ones that are so vulnerable
to developing acute phosphate nephropathy
And finally, for medication
induced crystalline nephropathies,
it's most important at the time that it's
occurring to remove the offending drug.
07:44
Now let's go back to that case
again of that HSV encephalitis patient.
07:48
A drug like acyclovir is critical
for them in order to get better.
07:53
So I can't keep that drug off completely, but
what I can do is I can administer a lot of volume
in the form of isotonic saline
and then again retry that drug
once that patient's
volume status is optimized.