a United States Army Medical Department Continuing
education program
diagnosis of rejection
with john D.
Welcome Lieutenant Colonel U.S.
Air Force Medical Corps Chief transplant
unit Wilford Hall U.S.
Air Force Medical Center.
Lackland Air Force base.
Despite almost 20 years of experience in renal
transplantation.
Now the early diagnoses of graft
rejection prior to significant insult to the
graft remains one of the most difficult and
complex ng problems in clinical transplantation.
Can we have the first slide please
from one thinks of rejection.
He thinks of it in a path a physiological
consequences.
These consequences can divided into three areas,
can be divided into three areas The
immunological nature of rejection,
the path of physiological alterations and
the pathological sequence.
The ecological nature has been discussed earlier this
morning and experts in the field will also discuss
the pathological sequence.
So we will devote our remarks
towards the path of physiological alterations.
These in my mind are extremely important because
frequently this is the only information the clinician may
have to make the diagnosis of rejection.
The path of physiological alterations can be
classified as chemo,
dynamic,
glamorous,
tabular and urinary
as stated before.
A knowledge of this data is very
important as it is upon this data that the
physician must depend to make his
diagnoses very frequently.
It may be the only data that he has.
The classification of rejection in general use
today is divided into
hyper cute,
acute and chronic hyper
acute rejection is a rapidly
progressive destructive process that
usually occurs within minutes to hours following the
transplant today,
we really have no successful method of dealing with this type of
rejection.
Therefore,
I'm not going to discuss it any further
is usually not a dubious problem that you're
dealing with.
When this occurs,
acute rejection is a process that
occurs between days and even
two up two years.
Post transplant,
it has been discussed in some detail today.
The sailor changes etcetera.
Since this is a reversible lesion and the one that we
usually have the most success with this will
probably this will be the topic of my discussion.
Chronic rejection is a rather insidious
process is characterized by slow
deterioration and final loss of graph graph
function at the present state of the art.
We really aren't able to control this and have no successful
means of treating it over a prolonged period of time.
The earliest alteration in acute rejection,
there's a disturbance in the hemo dynamics.
These changes are present prior to the clinical evidence
of deterioration in renal function
and is initially results of the shunning of
blood away from the cortex to the medulla
with a corresponding decline in gomorrah and
tabular function.
The shunning that we see is probably due to vessel spasm
and associated a demon that results from immunological
reaction.
As the process continues.
The cortical blood flow further decreases,
resulting in decreased camera function,
which results in a decreased sodium delivery to the distal
tubules.
T bills is reflected in a loss or decrease of
sodium excretion as the process
continues the total blood flow to the graph
deteriorates in the face of an increasing resistance
from vessel spasm vessel and
epithelial swelling micro thrown by an
increasing interstitial edema resulting from the
gemological vascular injury and adama.
Unfortunately,
these changes lead to further damage,
creating a rather vicious cycle that will ultimately
result in death of the graph unless they are altered.
The decrease in gomorrah filtration and tubular
function can initially be detected by a decrease in
heparin clearance.
This is followed in 24 hours by detectable decrease in the
creatinine clearance and in 24-48 hours
by rising serum creatinine.
This chemical and immunological damage in the
primarily membrane results in an increased
permeability of that membrane.
This is characterized by a loss of excessive amounts
of protein in the field.
Trade as a damage to the membrane increases during the
rejection and ischemic episodes
larger and larger molecular eight membranes
become present in the urine.
A variety of tubular d arrangements in the
handling of sodium bicarbonate,
phosphate,
chloride and hydrogen irons are seen during
rejection.
Renal tubular acidosis,
hyper chlorine,
mia,
glucose,
urea amino acid urea and foss materia may
occur several days prior to the clinical evidence
of rejection,
such as arising Bunn correct name
due to the ischemic changes in the tubular cells,
there is a compensatory shift from anaerobic
too,
from aerobic to anaerobic metabolism and
enzymes such as likely D hydrogenated alkaline
phosphates and listen,
enzymes may appear in the urine urinary
firebrand split products and increased numbers
of Lucas sites,
neutrophils and red blood cells may also appear
fever,
malaise anorexia and a general feeling of poor
health are frequently associated with the early stages of
rejection.
Unfortunately,
many of these changes also occur in other conditions such as
infection,
making the diagnosis somewhat difficult.
In an attempt to define the criteria that would aid
us in uh
recognizing and initiating
treatment of rejection episodes.
Early in their course,
we attempted to establish a
protocol or at least a list of signs that we could
depend on.
To do this.
We set a criteria major and minor signs.
In order to make the diagnosis of rejection.
We have chosen to use two majors.
One major or one or two miners are four minors as
the diagnostic criteria in which we would start our immunosuppressive
protocols.
The blood studies that we have utilized are those
probably utilized in most centers,
although not always consistently
are standardized,
are rising creatinine depending upon the
degree of rise,
whether whether it be a major and minor sign the same
for the Buon chloride and the white blood
cell count.
The urine studies that we depend upon our
volume threatening clearance,
sodium excretion,
the presence of lymphocyte in the urine and
protein.
The physical findings that we have found useful
are gaining weight,
swelling of the kidney.
Our graph characteristics on physical exam,
hypertension and fever.
To augment these particular
criteria.
We have also utilized serial renal
scans.
These scans.
We first began 24 hours after the transplant
and then performed the follow up scans every
2-3 days.
A typical example of the case of a case
in which this has been most beneficial was this young
lady who received a transplant on
18 September at this
point in time,
she had a normal technique,
easy um flow study which is depicted on this
slide.
Her following studies were normal in her clinical
clinical condition appeared very stable.
And on 10 October a scan revealed at a
12-16 2nd flow
12-16 seconds into a flow study.
Some deterioration of the flow,
the technician flow at this
point in time.
All of our parameters that we normally measure for
rejection were normal.
On the 11th the following day after this scan,
her her creatinine clearance began to decrease and she
became febrile On 12
October.
Her scan showed further deterioration in the
flow and uh
immunosuppressive.
I mean rejection therapy was instigated
on 15 October.
There shows there was a slight improvement in the flow
and her clinical course
followed rapidly behind this improvement in scan
with a dropping of her sim card and an improvement in her
creatinine clearance and clearing of her fever.
The hip Iran aspect of the scam.
We also utilized to determine what is
happening on the scam.
This is the hip Iran study.
This young lady had on the 10th of
october,
which unfortunately I do not have the slide for the
18th showed slight deterioration in her handling
of hippie ran her up taking clearance
On 12 October.
There was even further deterioration again uh
strengthening our feeling that we were dealing with the rejection on the
10th and clinically dealing with rejection.
On the 11th,
on the 15th of october.
After four days of him of uh increased doses
of selenium Pedro,
she had improvement in her hip here and study the
following reno grams.
Further substantiate the findings
Showing on 18 September a very
nice renal flow rate,
a good bladder uh concentration
On the 10th,
there was some flattening of the renal flow study with
some decrease in the accumulation of a die in the bladder
on the 12th.
Further deterioration and on the 15th
some improvement
thus far in our in our series of patients,
we have not had to utilize our terry ah graffiti to
diagnose rejection.
We have utilized it in certain instances where
we have experienced acute rejection that is not that does not
appear to respond to our uh to our
rejection therapy in an attempt to decide if
a graft is salvageable or not,
to get an idea of the radiological changes.
This is a normal arteriogram that's performed in a young
man who experienced uh no urine output
shortly after surgery.
And uh we felt that he could possibly
have occlusion of his artery.
Therefore,
an arteriogram was performed fortunately.
It was only a acute tubular necrosis which
rapidly cleared here.
You can see
that the outline of the kidney is very nicely
depicted.
The small temporary cortical vessels are filling.
There's no spasm of the vessels of the vessels,
there's no beating.
In the same series of studies.
We thought we see a very nice Neffa
graham.
And another side benefit is that you
can see the renal veins.
This was what we would have to clear.
This is what the radiological libertarian.
We also call a normal arteriogram and a transplant
patient.
The following slide is that of a young 23 year old male
who received a living related draft
and experienced an acute the an old set of acute
rejection approximately two weeks following the transplant
prior to that time.
His function had been quite adequate.
Despite rather intensive
anti rejection therapy,
his function did not improve
approximately a week and a half,
a week and a half into his acute rejection course.
His urine output was very low and his
crafting and be um,
are continuing to climb to determine
if increasing our our continuing the
the rejection therapy was indicated.
We felt that an arteriogram might give us some information.
As you see on this arteriogram,
there is some stretching of the vessels.
There is loss of that nice cortical outline that we saw
in the normal study by loss of flow into the
Treasury temporary vessels
from the results of this arteriogram,
we thought that we still had a salvageable graft.
But unfortunately,
that did not prove to be the case.
And the young man lost his kidney several weeks later.
The next arteriogram is that of a
young 19 year old male who received a one energy match
cadaver kidney,
who experienced a rather acute
on a rather acute rejection episode
approximately one week following the transplant,
that was reversed by increasing his steroid
therapy.
Following a tapering of the drugs he immediately
rejected again.
And at that point in time we instigated,
we instituted uh again,
repeat increased steroid
uh therapy and
he failed to respond to this again,
we utilized our terry og ra fee to see if we had a graph that was
worth continuing
continuing the rejection
therapy this young man shows.
And fair,
I think you can see this beating of
the secondary vessels of his
graft,
pruning of the vessels,
but no particular arterial spasm.
Again,
we felt that this kidney might be salvageable.
But unfortunately,
he too went on to reject his kidney when
it became apparent that our immune suppressive
therapy was inadequate.
And we ceased it.
The following slide is an arteriogram of a
34 year old female who received a two energy
match cadaver graft,
who experienced a rather marked onset of
acute rejection going from apparently normal
function to complete allegory Yuria.
In two days accompanied by high spiking fevers.
An arteriogram was likewise performed on her when
our immune suppressive therapy appeared not to have
any effect and she was returned to dialysis.
In this particular study,
you can see mark spasm of the arenal
artery going into the arena to the bifurcation of the
arenal main renal artery into its branches.
This may be a very ominous sign because this young lady
rapidly lost her graph despite our efforts
of trying to save it.
An intravenous polygram can on occasions also be
very helpful in diagnosing early
rejection.
Fortunately,
we had a nice situation in which to see.
This is something that is not usually seen.
This is an ivp from a
21 year old male who received a two engine match,
living-related kidney.
As standard in our program,
we obtain an IVP on the fifth post update,
hoping to get a good study of the your it'll
anatomy or the collecting system before rejection
occurs so that we can at least rule out
or uh have
some security in the fact that we don't have a
severe anatomical problem in this
particular situation.
This particular patient,
he had a functional obstruction of the ureter
mile but probably secondary to your
eternal edema at the systematic site
resulting in a mouth hydro Euro.
To the striking thing is that all of the pelvis and the
Euro to dilated.
There's no dilatation of the calluses,
which one normally would expect to see.
But you can if I think you can pick it out on this,
there is marked edema of the remote capella
which at the time we weren't sure what this meant.
But two days later we were quite certain what it meant is he
developed a rising B.
One and creatinine where they fall in.
His creatinine clearance slides off.
Please.
Despite all of these manipulations
methods etcetera.
Making the diagnosis of rejection,
we're still depending upon rather severe changes in the
graft uh as depicted by its
function before we can make the diagnosis and
institute therapy,
there's no doubt that we're losing some
some areas of the graph that we will probably never
recover.
Therefore it is imperative that we continue to search
for better methods of detecting rejection.
And there is some probable hope in the gemological studies
that we mentioned earlier this morning
diagnosis of rejection
with john D.
Well call Lieutenant Colonel U.
S.
Air Force Medical Corps Chief transplant
unit,
Wilford Hall U.
S.
Air Force Medical Center.
Lackland Air Force Base
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United States Army Fort Sam Houston
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