Anemia of chronic disease - Kidney Transplantation: Ask Dr. Matthew Cooper

Anemia of chronic disease




- [Voiceover] So anemia of
chronic disease is the second
most common cause of anemia
in hospitalized patients
and it's a type of microcytic anemia,
microcytic anemia.
So, that tells us that
anemia of chronic disease
is somehow due to a problem,
a problem in producing hemoglobin
because we know that
all microcytic anemia's
result from a problem
in producing hemoglobin.
The second thing that's really
important about this disease
is that it's always, always,
always, always related
to some inflammatory condition.
So that's to say that
there must be some source
of inflammation in the body
for this disease to result.
Now, anemia of chronic disease
has absolutely everything
to do with the molecule, hepcidin
which is a polypeptide,
is just a fancy term
for a chain of amino acids
that's produced by the liver
that serves as the bodies
major iron regulator.
And by regulator, I mean that when
the serum iron levels are low,
when the bodies iron
levels are running low,
there's a low production of hepcidin.
But, when the bodies iron
storage are running high
or when there is excessive
amount of iron in the body,
the liver increases
it's hepcidin production
and it does this because the hepcidin
then turns around and
it decreases serum iron,
decreases serum iron.
And it does this, it decreases serum iron
in a couple of different ways.
And to understand how it decreases it,
I guess we'd have to go
back for a couple seconds
to understand iron physiology.
So, we talked about how iron
is absorbed it the duodenum,
but something we didn't mention is that
at the base of these cells in duodenum
is this channel called ferroportin
and ferroportin is what allows the iron
to go across these cells in the duodenum
and be absorbed into the bloodstream.
Now hepcidin comes in and it blocks
the ferroportin channels and by doing so,
it inhibits the absorption
of the iron from the gut.
So, that's the first way
in which hepcidin acts
to decrease serum iron levels.
Now, I'm going to scroll down,
scroll down just a little,
okay, so secondly, let's
take a look at the liver,
and here's a blood vessel
that has blood in it
and we know that blood has
lots of red blood cells in it.
And every 120 days or so, each
one of these red blood cells
is taken out of commision, it's retired
and it's degraded by cells in
the liver called macrophages.
So, these red blood
cells are broken down by
the macrophages and
inside the red blood cells
we know we have lots of hemoglobin
and the hemoglobin has iron in its center,
and the iron that is
released from the degradation
of the red blood cells
isn't just thrown away,
instead it's saved and it's recycled
to be used later on to
make new red blood cells.
So, what hepcidin does in this scenario
is it comes in and it
inhibits the degradation,
it prevents a degradation
of these red blood cells,
and it does so to prevent this iron
from being saved and
being recycled later on.
So this is the second
way in which hepcidin
acts to decrease serum iron.
So, moving to the side just a little,
so just to quickly
summarize what hepcidin does
is it decreases serum iron by decreasing
the absorption of iron from the gut
and decreasing recycling by inhibiting
the degradation of red blood cells.
And, in normal people,
hepcidin is released
in response to an increase
in serum iron, right?
So it's essentially the
bodies compensatory mechanism
to deal with too much iron.
Now, in the case of
anemia of chronic disease,
hepcidin is released in response to
any inflammatory condition,
so any condition in which
there's inflammation.
So firstly, what do I mean
by inflammatory condition?
Well, I mean things such as infection,
because we know our body
mounts an inflammatory response
to protect us from infections.
Now I also mean things like cancer,
who's malignancies a pretty
inflammatory condition
and also autoimmune diseases,
autoimmune diseases,
and usually what comes to
mind with autoimmune diseases
is things like rheumatoid
arthritis or lupus
but really any autoimmune condition
can do the same thing.
So these are just three
of the most common causes
of inflammation but really
there's several other disorders
that could lead to the same response.
Now, when there's any source
of inflammation in the body,
the body releases cytokines
or small signalling molecules.
And these cytokines cause
an increase in hepcidin production.
The hepcidin then decreases
the absorption and recycling
of iron to lead to a
decrease in serum iron.
That much we've already established.
Now this decrease in serum iron
then leads to a decrease
in hemoglobin production,
and that decrease in hemoglobin production
is what leads to the anemia.
And that's how an inflammatory condition
or a chronic disease leads to anemia.
Now, I guess something that we
haven't really addressed very well,
is why would you want
there to be a decrease
in serum iron in response to
an inflammatory condition,
why does this pathway even occur?
And the response to that
is really important.
So, in conditions such as, for example,
such as infection, bacteria
thrive off of iron.
They use it as an
essential nutrient to grow.
So really what the body
does is quite smart,
it essentially plays
keep-away with the iron.
So it releases hepcidin
to keep away the iron
so that the bacteria can't use it to grow.
And really, this same thing occurs
in cancer and in autoimmune condition
in which these cells use iron
as an essential nutrient.
So that is essentially the background
and the pathophysiology of
anemia of chronic disease.

https://www.youtube.com/watch?v=EkFUb3L040E


Kidney Transplantation: Ask Dr. Matthew Cooper




I'm Dr. Matthew Cooper, I'm the director of
the Kidney and Pancreas Transplant Program
here at the
MedStar Georgetown Transplant Institute
which is a component of the
MedStar Georgetown University Hospital.
I have the privilege of overseeing
the Kidney and Pancreas Programs
for Georgetown Hospital and for
Washington Hospital Center.
I've been involved in transplantation now
for over 12 years,
having trained at the
Georgetown University Medical School
and then completing residency
in the Midwest in Milwaukee
in my fellowship at Johns Hopkins.
I have the privilege of seeing patients
who I think unfortunately
are becoming more and more
of a health epidemic,
those that have end-stage kidney disease
from real common problems
like hypertension and diabetes.
We look to try and offer them
a better answer than being on dialysis
because as I tell our patients,
really dialysis robs people
of years of life.
So my job as a transplant surgeon
is to provide them the gift of life
through transplantation
of an organ either through
a deceased owner or a living donor.
In terms of pancreas transplant
for people that have type 1 diabetes
or insulin-dependant diabetes,
we're really able to give these people
new lives as well, to be able to avoid
checking blood sugars every 4-5 times a day.
We can even look into combining
both of those transplants,
receiving both a kidney and
a pancreas transplant, so really
the ability to enjoy both
of those successes
in kidney and pancreas transplantations.
I tell people I have the greatest job in
the world and its not an understatement.
The pleasure of forming our relationship
with our patients that last decades
into the future, well beyond our initial
meeting with them,
in terms of a surgical specialty,
we cure disease by putting something
in someone rather than
taking something out.
We also speak for the donors
and the donors' families,
making sure that everybody
who has the joy
to receive that gift of life recognizes
what a tremendous opportunity
the gift that they've received.
What comes back to us
is a transplant team and an enormous
responsibility is that stewards
are a very valuable resource.
But again,
I come to work every day
with a new enthusiasm
and invigoration for what I do.
I get to meet some wonderful people
who really look to me for opportunities
better than what they have right now,
I like to think that we embrace that
and try and work closely with
a very large team here at the MedStar
Georgetown Transplant Institute
which is something again that attracts me
to this job as I get to meet
and work with very committed,
very dedicated people who are
all in this together to make
a better life for somebody else.
The MedStar Georgetown
Transplant Institute
is primarily concerned about outcomes
and safety
and being certain that we're always
looking for a way
to move transplantation forward.
I was fortunate to be offered
this position to come to Georgetown
and for me it was one of those things
that was the opportunity
to come to an institution that I know
that places outcomes and safety
above everything else. There are many
transplant programs
in many institutions that are perhaps
unfortunately looking at
the wrong statistic, which is the numbers
of transplants that are completed.
Now yes, that's something that absolutely
we're interested in doing,
it's providing the gift of transplantation
to as many people as we possibly can,
but ultimately, we want to be able to look
back and say that we've done
good things for good people
through a good opportunity
and a good team. And I think
that's the one thing
that transplants here at the MedStar
Georgetown Transplant Institute
has, will, and in the future always will
continue to focus on is making sure
that the outcomes... because we want
to be able to look at patients
and say that we're looking to make
your life better through transplantation.
We want to be able to look to families
of people who've donated their organs
through the deceased donations and say
that we've been
cautious and careful and considerate
in making sure that the individuals
who receive your transplant
truly appreciate that gift of life
and they're going to take care of it,
we want to make sure that we're able
to look at living donors and say
that we recognize the sacrifice
that you're making and that
we wouldn't put you in harm's way if
we didn't think that it was safe for you
and that the recipient who again
is receiving your organ
is appreciative of the tremendous
gift that you're receiving.
There's really two broad categories that
put people in need for organ transplants,
namely kidney transplants.
The most common are diabetes
and hypertension,
number 1 and 2 by far.
The trouble with both of those problems is
that unfortunately many people
either don't know they have those problems
or they unfortunately don't seek help
for treating those problems and they go
on to cause kidney disease
and ultimately end-stage kidney failure.
The other problems are more
genetic problems,
people can be born with kidney problems,
either the kidneys don't develop properly
or they grow improperly or they have
some genetic condition
which ultimately leads to failure
of those kidneys.
So we look at all of those conditions
as being very similar in that
their ultimate result of
end-stage kidney disease.
We still believe it's better treated
with transplant than dialysis.
Dialysis really should be looked upon
as a stepping stone for kidney transplant.
It's important for folks that are
on dialysis or are approaching dialysis
look for transplant centers like we have here
at MedStar Georgetown Transplant Institute
so that we can look to find a way
to avoid that stepping stone altogether,
because we can't transplant someone
before they've actually reached dialysis.
There's about 90,000 people across
the United States
that are waiting for a kidney transplant.
Takes your breath away at times.
Now the truth is that because of that
and the numbers of deceased donor organs
haven't changed to keep up with
those numbers of increases on the lists,
the time in which people wait for
a transplant unfortunately does.
So the average wait time for
a deceased donor transplant
based upon people's blood type
could be somewhere between 3-5 years
and that's the numbers that we quote here at
the MedStar Georgetown Transplant Institute
is that it can be some 3-5 years after we
initially see somebody for a transplant.
Which means again, the relationship
continues many years after
the initial visit with the transplant center,
we have to be
regularly in touch with one another
with any changes in medical health
or conditions. We know that this relationship
is something which is important
not only to the patient, but it's important
to us, it's important to the donor,
so we always have to be appreciative
of those open lines of communication
that we don't lose track
with one another.
If an individual contacts our institution
we have them come
to our transplant center
and they're seen by
what we call a multi-disciplinary team,
means many people,
everybody wearing their particular
specialty hat,
gets the opportunity to meet
that individual
and as a team we put
all that information together
as well as try and gather information
from a referring physician
or from a previous hospitalization
so that we can say
it's safe to do particularly 2 things:
1, that it's safe to have an operation,
which usually means that we have
to make sure that people
from a heart and a lung standpoint
are safe to go into the operating room,
and 2, we need to make sure
it's safe for people to have
the immunosuppressant medications,
the medications that allow
the immune system to accept
the transplant.
We have to be certain that it's safe
to give people medications
which increase the risk for things like
infections and even things like cancers.
So we do a very thorough workup
from top to bottom
to make sure that we're making people's
lives better
and certainly don't want
to make them worse
which means we take no shortcuts,
we utilize the resources
we have available both here at our
institution and with referring doctors
and always look to partner with our
referring physicians nephrologists
and endocrinologists so that we can provide
the best possible care for the patient.
There is a potential way in which
people can receive transplants
via living donor. Not everyone unfortunately
has a living donor available to them
but if we look again very carefully
at the outcomes for living donor
versus deceased donor transplants,
we know that results in terms of
how long the graft or the kidney will last
in the recipient
is about twice as long for a living donor
as compared to a deceased donor.
So that means that we ask people
to seriously consider that,
not only because of that information
but also because of the waiting time
for a deceased donor transplant.
Then we have to be very honest
and think of options
for living donor transplants.
It's important to appreciate
that the ultimate goal
in all living donor transplantation
is the safety of the donor
and that's something that as
an institution
here at the MedStar Georgetown
Transplant Institute
we place as the highest priority
which is the safety of the donors.
We have to be very careful
and we never want to hurt one person
trying to help someone else
so the process requires
a very large group of individuals who again
look very carefully at that donor
to say, is this safe for the person
to go forward
to have an operation or a procedure
performed that they don't need
and we find the it is not right
for everybody,
that it's not that we're trying to deny
somebody the opportunity
to help someone they care about,
but we have to always protect the safety
of that individual as well as protect
the safety of transplants.
A large number of people actually
come to our institution
and are able to move forward
as being a living donor.
It's important to appreciate that
that individual doesn't necessarily
need to be related to the recipient,
that it could be somebody
who they have again a close
relationship with but is not genetically
related to that person,
because there's many things that
we're able to do now
that allow living donation
to move forward
separate from what we call
a negative cross-match
or having the same blood type
as the donor and recipient.
So I think been very important for people
to think outside of their family tree
about who may be a living donor
and be able to bring about
that gift of life for the recipient.
So donors and recipients can really have
no relationship to each other whatsoever.
They don't need to be the same race
and if they're different blood types
that isn't important as well.
It would be untruthful to say that
there isn't any risks
but the fact is that again with
the specialties and the institution
here at the MedStar Georgetown
Transplant Institute
we have a group that is truly committed
to making sure that we eliminate
all potential risks, that we evaluate
the donor completely
and be certain that going into the
operating room we make the risk
as small as possible
and we're certainly always in communication
and open and honest
about what those risks may be
and sometimes again, we have to tell
a donor that the risks are too high
but when we look very carefully
at the outcomes across the county
and the outcomes
at our institutions
we have found that safety
has been in fact yes,
something that we've achieved
and something that we're always
going to continue to look for
as our top priority.
We never know when that phone call
or that kidney is going
to become available for the recipient
and sometimes it's important
to appreciate that there may be
a false alarm,
sometimes our efforts are to try
and get that kidney transplanted
as soon as we can because we know
the shorter the time that it takes
the transplant to happen,
typically the better the outcome
but sometimes things happen towards
the end of the process
where a transplant just isn't safe
to move forward,
that it keeps people at the same place
on the list and ultimately
they will get their transplant but
at a later time.
So many years ago when people became
interested in being a living donor
we found that they weren't either
the same or compatible blood-types
or had what we call
a positive cross-match,
meaning, when we put donor and
recipient's blood together,
they have a reaction which would
not allow the transplant to happen,
we would unfortunately have to tell
both the donor and recipient,
"I'm sorry, you have to look
for another living donor."
You know, the turn of the century and
technology and electronic communications
that we have available nowadays
really made that seem very short-sighted
and there's a lot of different things
now that we're able to do
that would allow living donation
to happen in all of those situations.
So for some donor-recipient pairs
we're able to remove the incompatibility
for the recipient, we call that a process
of desensitization
and there're some pretty exquisite
and pretty elaborate techniques,
safe, but still require the commitment
and the dedication of a number of
very dedicated staff here to allow
that living donor transplant to happen
so that we remove the incompatibility.
We also have things called
"paired exchanges", where multiple
donor-recipient pairs
who were incompatible with each other
may be compatible with other exchanges
and we allow living donor transplant
to happen for a number of different pairs
perhaps not with their intended recipient
but with another donor
that we can bring about multiple
living donor transplants
and sometimes that can occur
over the course of a couple of days
and sometimes we can allow the process
to extend over a couple of months
and we call that a chain.
They don't go on vacation.
They can't just go away
to visit a relative who may be
on the other side of the country.
They can't even disappear for days
on end if they can't get back
to the dialysis center, because again
they need the machine
not only to keep them alive
but also because without the machine
they actually feel pretty badly.
So even days when they're not on dialysis
a lot of times their body... or they're
physically just feeling
as if they need dialysis. So it is again
a pretty destructive and troublesome life
for people.
Overall, if you look again at the risks
and the benefits of transplant
versus that of dialysis if falls clearly
on the sides of benefit for transplant.
One of those risks associated with
dialysis is unfortunately
that dialysis has an increased risk
of things like heart disease,
of strokes and peripheral
vascular disease.
People who are on dialysis
can unfortunately need
things like blood transfusions which
can lead to what we call
developing antibodies in their bloodstream
so it can make it
more difficult for them to receive
a kidney transplant.
So again, if we can try to avoid dialysis
we know that those outcomes
are better not only long-term for the
survival but allow us more opportunities
through transplantation by avoiding
sensitization as we call it,
that's the word for people when
they develop antibodies.
So again, dialysis and transplant -
two ways of taking care
of end-stage renal disease.
One is clearly better than the other,
dialysis is but merely a stepping
stone to the transplant
which is why we want everybody to come
and see us as soon as possible.
We've learned more about the safety
of living donation and have
better medications to improve the outcomes
for transplantation
as well as mechanisms and ways in which
we can allow a living donation
to occur through things we call
paired exchange,
where donors and recipients who may not
be the same blood type
or may have a positive reaction
when we put their bloods together,
we can put donor and recipient pairs
together to allow recipients
to receive the benefit of living donor
transplant
from someone who may not have been their
intended donor
but yet the recipients all see the benefit
of living donor transplant
that we talk so much about.
The average kidney transplant from a
deceased donor lasts about 10 or 11 years.
From a living donor transplant it's
closer to 17 or 18 years.
We of course always want to make sure
that the first transplant is the best one
and has the best outcome,
but if we need a second transplant
we're going to think the same thing
about the second one.
But it is important to understand that
there may in fact be a need
for a repeat transplant depending upon when
someone received their first transplant.
The donor process is one which again
we take very seriously.
A donor can contact the institution here
at the MedStar Georgetown Transplant
Institute and the process begins.
We ask them to fill out a questionnaire
which gives us some
baseline information about the history
of the donor
and any significant medical history that
would allow us
to make the decision more clear.
The donor then comes to see
a group of individuals from various
specialties in the hospitals,
surgeons, nephrologists, social workers,
financial people.
Important to appreciate that the donor
does not incur expenses
for the process of being worked up
for a donor or for the hospitalization.
The recipient's insurance does pay for that,
but we do want to make sure
that the donor can afford to do things like
taking off time from work
or for child care, because those expenses
we cannot pay for.
The donor also sees somebody who has
a very important role in the institution
called an independent donor advocate
whose job is, as the name says,
to be independent from the transplant center
and to advocate on their behalf,
to make sure again that everything
is very carefully looked at
to say that it's safe for this individual
to become a donor.
The process often requires other testing
including an electrocardiogram,
a chest X-ray and then another test
which looks at the arteries and veins
of the kidney that we actually
get in our radiology department,
we call that an MRI.
Patients may then need to see
other specialists in order to work up
other conditions which we need to say
are safe to go into the operating room.
Again, sometimes this takes a couple of
weeks, it may take a couple of months
but again I'd hope that the donors
and the families will feel comfortable
knowing that we're trying to make sure
that safety is the top priority
and if it takes an extra week or so
that was initially anticipated
for the donor to be clear, it's all because
we want them to go into the operating room
feeling comfortable that they've made
the right decision to be a donor,
that they're comfortable
that they chose
the MedStar Georgetown Transplant Institute
to have their donation done
and that when it's all completed
they can look back
and say that they're very
comfortable in what they did
and that they have no regrets
having done this.

https://www.youtube.com/watch?v=Y0XfaxC9cLM