Transplant Digest - Fall 2010, Issue No. 9 - St. Michael's Hospital

edside.
Fall , I sue No.
•
infection
(con’t on page 3)
Transplant
Digest
Fa l , Issue No.
Regula readers the Transplant Digest, wi l notice that
we now have an exciting new layout an design. This
change is part of the ro l out of renewed St. Michael’s
brand.
St. Michael’s new image captures its reputation for
compassion caring along with its reality as a
modern, sophisticated, innovative organization.
Our new tagline “ Inspired Care. Inspiring Science.”
emphasizes equa ly our three roles – as hospital
providing compa sionate care and a teaching
and research organization mitted to moving
knowledge an discovery from the cla sr om and the lab to bedside.
Dr. Samuel Silver, Resident in Internal Medicine
New Image of Transplant Digest
Heart Disease after Kidney Transplantation -
Are the Risk Factors the same as the General Population
Cardiovascular disease (CVD), involving such conditions In fact, researc ha shown tha the FRS underestimates
as heart a tacks and bypa surgery, is known to decrease CVD kidney transplant patients, especia ly those
dramatica ly after kidney transplantation. However, CVD patients a the highest risk for developing CVD. This
is more prevalent in kidney patients than the is likely because kidney transplant patients have other
general population. Even young transplant recipients important risk factors to consider. These include:
experience close to 10-fold increase CVD. Therefore,
Pre-transplant cardiac and chronic kidney disease
CVD is clearly significant barrier to staying healthy
post-transplantation.
Post-transplant exposure to cardiac risk factors
In order to prevent CVD, doctors a temp to predict •
which patients are most for developing CVD i munosu sant medications, acute rejection, and
using the Framingham Risk Score (FRS). The is the infection
most mon tool used determine a patient`s CVD At St. Michael`s Hospital (SMH), we are using
risk. It combines traditional cardiac factors (age, information on our transplant patients improve the
sex, total cholesterol, high density lipoprotein, smoking
identify cardiac risk factors that are specific
status, diabetes, and bl od sure) to identify high risk to kidney transplant patients. We are now studying
patients who would benefit fro medications protect traditional, novel, and transplant-specific risk factors their heart, such as aspirin, bl od pressure drugs, and determine which factors are most important in kidney
cholesterol-lowering drugs. Unfortunately, the FRS may transplant patients. Novel risk factors such as C-reactive
not be an a curate indicator of risk kidney protein, microalbuminuria, uric acid, vitamin D, and
patients.
TRANSPLANT DIGEST
Fa l 2010
(con’t on page 3)
New Image of Transplant Digest
Heart Disease After Kidney
Transplantation
From the Editor’s Desk
Contact Information
Regeneration
Post-Transplant Chat
Smoking and Kidney
Transplantation
Coping With Chronic Renal
A lograft Failure
An Introduction to Diabetes and
Kidney Transplant
ADVAgraf: Once Daily
Alternative to PROgraf
In this i sue ...
TRANSPLANT DIGEST
Fa l 2010
Coping With Chronic Renal
A lograft Failure
An Introduction to Diabetes and
Kidney Transplant
ADV A graf: A Once Daily
Alternative to PROgraf
In this i sue ..
Transplant
Digest
Fall 2010, Issue No. 9
New Image of Transplant Digest
Regular readers of the Transplant Digest, will notice that
we now have an exciting new layout and design. This
change is part of the roll out of renewed St. Michael’s
brand.
St. Michael’s new image captures its reputation for
compassion and caring along with its reality as a
modern, sophisticated, and innovative organization.
Fall , Issue No.
Our new tagline “ Inspired Care. Inspiring Science.”
emphasizes equally our three roles – as a hospital
providing compassionate care and a teaching
and research organization committed to moving
knowledge and discovery from the classroom and the lab to the
bedside.
Transplant
Digest
New Image of Transplant Digest
Regula readers of the Transplant Digest, will notice that
we now have an exciting new layout and design. This
change is part of the roll out of renewed St. Michael’s
brand.
St. Michael’s new image captures its reputation for
compassion and caring along with its reality as a
modern, sophisticated, and innovative organization.
Our new tagline “ Inspired Care. Inspiring Science.”
emphasizes equally our three roles – as a hospital
providing compassionate care and a teaching
and research organization committed to moving
knowledge and discovery from the classroom and the lab to the
bedside.
Heart Disease after Kidney Transplantation -
Are the Risk Factors the same as the General Population
Dr. Samuel Silver, Resident in Internal Medicine
Cardiovascular disease (CVD), involving such conditions
as heart attacks and bypass surgery, is known to decrease
dramatically after kidney transplantation. However, CVD
is more prevalent in kidney transplant patients than the
general population. Even young transplant recipients
experience close to a 10-fold increase in CVD. Therefore,
CVD is clearly a significant barrier to staying healthy
post-transplantation.
In order to prevent CVD, doctors attempt to predict
which patients are most at risk for developing CVD
using the Framingham Risk Score (FRS). The FRS is the
most common tool used to determine a patient`s CVD
risk. It combines traditional cardiac risk factors (age,
sex, total cholesterol, high density lipoprotein, smoking
status, diabetes, and blood pressure) to identify high risk
patients who would benefit from medications to protect
their heart, such as aspirin, blood pressure drugs, and
cholesterol-lowering drugs. Unfortunately, the FRS may
not be an accurate indicator of risk in kidney transplant
patients.
Transplant
Digest
New Image of Transplant Digest
Regula readers of the Transplant Digest, will notice that
we now have an exciting new layout an design. This
change is part of the ro l out of renewed St. Michael’s
brand.
St. Michael’s new image captures its reputation for
compassion and caring along with its reality as a
modern, sophisticated, and innovative organization.
Our new tagline “ Inspired Care. Inspiring Science.”
emphasizes equa ly our three roles – as a hospital
providing compa sionate care and a teaching
and research organization commi ted to moving
knowledge an discovery from the cla sroom and the lab to the
Heart Disease after Kidney Transplantation -
Are the Risk Factors the same as the General Population
Dr. Samuel Silver, Resident in Internal Medicine
Cardiovascular disease (CVD), involving such conditions
as heart a tacks and bypa surgery, is known to decrease
dramatically after kidney transplantation. However, CVD
is more prevalent in kidney transplant patients than the
general population. Even young recipients
experience close to 10-fold increase CVD. Therefore,
CVD is clearly a significant ba rier to staying healthy
post-transplantation.
In order to prevent CVD, doctors a temp to predict
which patients are most at risk for developing CVD
using the Framingham Risk Score (FRS). The FRS is the
most co mon t ol used to determine a patient`s CVD
risk. It combines traditional cardiac risk factors (age,
sex, total cholesterol, high density lipoprotein, smoking
status, diabetes, and pressure) to identify high risk
patients who would benefit fro medications to protect
their heart, such as aspirin, blood pre sure drugs, and
cholesterol-lowering drugs. Unfortunately, the FRS may
not be an a curate indicator of risk in kidney transplant
patients.
In fact, researc ha shown that the FRS underestimates
CVD in kidney transplant patients, especia ly those
patients a the highest risk for developing CVD. This
is likely because kidney transplant patients have other
important risk factors consider. These include:
Pre-transplant cardiac and chronic kidney disease
• Post-transplant exposure to cardiac risk factors
i munosuppre sant medications, acute rejection, and
At St. Michael`s Hospital (SMH), we are using
information on our transplant patients improve the
FRS and identify cardiac risk factors that are specific
to kidney transplant patients. We are now studying
traditional, novel, and transplant-specific risk factors determine which factors are most important in kidney
transplant patients. Novel risk factors such as C-reactive
protein, microalbuminuria, uric acid, vitamin D, and
In this issue ...
New Image of Transplant Digest
Heart Disease After Kidney
Transplantation
From the Editor’s Desk
Contact Information
Kidney Regeneration
Post-Transplant Chat
Smoking and Kidney
Transplantation
Coping With Chronic Renal
Allograft Failure
An Introduction to Diabetes and
Kidney Transplant
ADVAgraf: A Once Daily
Alternative to PROgraf
In fact, research has shown tha the FRS underestimates
CVD in kidney transplant patients, especially those
patients at the highest risk for developing CVD. This
is likely because kidney transplant patients have other
important risk factors to consider. These include:
• Pre-transplant cardiac and chronic kidney disease
• Post-transplant exposure to cardiac risk factors
•
immunosuppressant medications, acute rejection, and
infection
At St. Michael`s Hospital (SMH), we are using
information on our transplant patients to improve the
FRS and identify cardiac risk factors that are specific
to kidney transplant patients. We are now studying
traditional, novel, and transplant-specific risk factors to
determine which factors are most important in kidney
transplant patients. Novel risk factor such as C- reactive
protein, microalbuminuria, uric acid, vitamin D, and
(con’t on page 3)
New Image of Transplant Digest
Heart Disease After Kidney
Transplantation
From the Editor’s Desk
Contact Information
Kidney Regeneration
Post-Transplant Chat
Smoking and Kidney
Transplantation
TRANSPLANT DIGEST
Fa l 2010, Issue No. 9
In this issue ...
New Image of Transplant Digest
Heart Disease After Kidney
Transplantation
From the Editor’s Desk
Contact Information
Kidney Regeneration
Post-Transplant Chat
Smoking and Kidney
Transplantation
Coping With Chronic Renal
Allograft Failure
An Introduction to Diabetes and
Kidney Transplant
Heart Disease after Kidney Transplantation -
Are the Risk Factors the same as the General Population
Dr. Samuel Silver, Resident in Internal Medicine
Cardiovascular disease (CVD), involving such conditions
as heart attacks and bypass surgery, is known to decrease
dramatically after kidney transplantation. However, CVD
is more prevalent in kidney transplant patients than the
general population. Even young transplant recipients
experience close to a 10-fold increase in CVD. Therefore,
CVD is clearly a significant barrier to staying healthy
post-transplantation.
In order to prevent CVD, doctors attempt to predict
which patients are most at risk for developing CVD
using the Framingham Risk Score (FRS). The FRS is the
most common tool used to determine a patient`s CVD
risk. It combines traditional cardiac risk factors (age,
sex, total cholesterol, high density lipoprotein, smoking
status, diabetes, and blood pressure) to identify high risk
patients who would benefit from medications to protect
their heart, such as aspirin, blood pressure drugs, and
cholesterol-lowering drugs. Unfortunately, the FRS may
not be an accurate indicator of risk in kidney transplant
patients.
Advagraf: A Once Daily
Alternative to Prograf
In fact, research has shown that the FRS underestimates
CVD in kidney transplant patients, especially those
patients at the highest risk for developing CVD. This
is likely because kidney transplant patients have other
important risk factors to consider. These include:
• Pre-transplant cardiac and chronic kidney disease
• Post-transplant exposure to cardiac risk factors
• Transplant-specific risk factors related to
immunosuppressant medications, acute rejection, and
infection
At St. Michael`s Hospital (SMH), we are using
information on our transplant patients to improve the
FRS and identify cardiac risk factors that are specific
to kidney transplant patients. We are now studying
traditional, novel, and transplant-specific risk factors to
determine which factors are most important in kidney
transplant patients. Novel risk factors such as C-reactive
protein, microalbuminuria, uric acid, vitamin D, and
(con’t on page 3)
TRANSPLANT DIGEST
Fall 2010, Issue No. 9

From the Editor’s Desk
An important goal of Transplant
Digest is to impart kidney
transplant-related information
to both patients and health
care providers in a readable,
understandable form that will not
become outdated anytime soon.
To this end, we have strived to
cover the spectrum of important
problems that transplant
recipients may come across over
a number of Digest issues, meant
therefore to be kept together in
one place. In keeping with this
quest for originality, this edition
carries new articles on a broad
variety of topics, a few of which
will interest everybody, and all of
which will interest many.
Our medical trainees, the
doctors of tomorrow, obliged our
request to provide you with their
insights in to the risks for heart
disease after transplantation,
particularly smoking. For the
smokers among our patients,
may be these articles will finally
convince you to quit. We also get
many questions about growing
new kidneys in a test tube as
an alternative to transplant,
for which we have provided an
article written just for you by
one of our senior trainees. We
have a detailed explanation about
tacrolimus formulations from our
pharmacist, and an article about
coping with transplant failure
from social work. References
are provided for many articles
for those desiring further
information. Our nurses’ everpopular
post-transplant chat
covers the all-pervading problem
of anemia. All the authors and
staff will find your comments and
suggestions about Transplant
Digest to be most welcome.
Dr. Ramesh Prasad,
Editor
Contact Information
Dr. Ramesh Prasad – Editor
Meriam Jayoma-Austria, RN, CNeph(C) – Newsletter Coordinator
St. Michael’s Hospital
Renal Transplant Program
(across the hospital)
61 Queen Street 9th Floor
Toronto, Ontario, M5C 2T2
Phone: (416) 867-3665
Please send your comments or suggestions
of topics for future publication to:
jayomam@smh.ca
Disclaimer Note:
Views presented in this newsletter are
those of the writers and do not necessarily
reflect those of St. Michael’s Hospital or the
University of Toronto. Subject matter should
not be construed as specific medical advice
and may not be relevant to individual patient
circumstances. For all questions related to
your own health please contact your health
care provider.
Thank You Josie! All the best!
Jozenine Mislang covered Meriam’s one year maternity leave.
2

(con’t from page 1)
parathyroid hormone are of particular significance, as
they have gathered increased attention in the general
population, but have not been studied extensively in
kidney transplant patients. By routinely measuring
these values in kidney transplant patients at SMH,
we are in an excellent position to determine
if novel risk factors can help improve our
ability to predict CVD.
Thus far, we have found that the traditional
risk factors, especially diabetes and
smoking, which partly make up the FRS
remain important in kidney transplant
patients. Other important cardiac risk
factors include:
• Pre-transplant CVD
• South Asian ethnicity
• Acute rejection
• Delayed graft function
• Estimated glomerular filtration rate (eGFR)
We are currently trying to determine if any of
the above risk factors can improve
the FRS. Our hope is that one day
we might have a tool for kidney
transplant patients to accurately
predict which patients are at low
risk, moderate risk, and high risk of
developing CVD.
We would like to thank all kidney
transplant recipients who participated in
research at SMH in order to help current and
future patients.
Kidney Regeneration: A New Approach to Chronic Kidney Disease
Darren Yuen, MD FRCPC
Kidney regeneration has been a goal
nephrologists have been striving for
over many years. Recent advances in
bioengineering techniques and our
understanding of stem cells has brought
this goal closer to reality.
Bioengineering a scaffold for a new
organ
One of the critical challenges for
regeneration of any organ has been how
to organize the many different types
of cells that make up an organ into a
functioning system. Organs such as the
kidney are complex networks of various
cell types that interact with one another
in very specific ways. While researchers
have for years been able to grow different
kidney cells in culture dishes, they have
had difficulty organizing these cells into
functioning kidneys. Recently, however,
researchers in the United States have
reported the ability to create “scaffolds”
that help organize cells into proper
locations by removing the cells from
organs supplied by animal or deceased
human donors. Using the heart 1 , liver 2 ,
and lung 3 as examples, these researchers
were able to remove all the original
donor cells, and then seed the leftover
protein skeleton with new cells from
potential recipients. The new organs
were able to perform basic functions.
The importance of this advance is that
it allows doctors to potentially generate
organs that are made up of cells from
the proposed recipient, meaning that
theoretically we will not need to use
immune suppressing drugs to prevent
organ rejection. Interestingly, the first
such tissue-engineered transplantation
occurred in Spain in 2008, where a woman
received a new airway seeded with her
own cells. 4 While this technique has yet
to be applied to the kidney, the above
reports suggest that bioengineering
kidneys is likely something to expect in
the not too distant future.
Stem cells: a new source of kidney cells
Another major challenge has been
generating sufficient kidney cells to
regenerate kidney tissue (or to form
an entire new kidney). Classically, it
has been thought that most adult cells,
including many in the kidney, are not
able to grow and regenerate new cells
in large numbers. As we understand
biology better, we now recognize that
there are populations of adult stem cells
that possess the ability to regenerate
cells in the kidney and other organs.
Interestingly, the bone marrow has
recently been shown to harbour a
number of cell types that can help
protect and/or regenerate damaged
tissue in the kidney. 5 Work done at
St. Michael’s Hospital, in fact, has shown
that special cells from the bone marrow
appear to protect the injured kidney
from further damage in experimental
animal models. 6
Together, these exciting advances bring
the hope of protecting and regenerating
kidney tissue closer to reality. Research
into these areas is intensive and ongoing,
and hopefully will bear fruit in the near
future.
1. Ott, H.C., et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med 14, 213-221 (2008).
2. Uygun, B.E., et al. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med 16, 814-820.
3. Ott, H.C., et al. Regeneration and orthotopic transplantation of a bioartificial lung. Nat Med 16, 927-933.
4. Macchiarini, P., et al. Clinical transplantation of a tissue-engineered airway. Lancet 372, 2023-2030 (2008).
5. Rookmaaker, M.B., et al. Bone-marrow-derived cells contribute to glomerular endothelial repair in experimental glomerulonephritis. Am J Pathol 163, 553-562 (2003).
6. Yuen, D.A., et al. Culture-Modified Bone Marrow Cells Attenuate Cardiac and Renal Injury in a Chronic Kidney Disease Rat Model via a Novel Antifibrotic
Mechanism. PLoS ONE 5, e9543.
3

Post-Transplant Chat
Thelma Carino, RN, Jennie Huckle, RN and Fernanda Shamy, RN
POST-TRANSPLANT ANEMIA
1. What is anemia Is it bad
Anemia is defined as a hemoglobin level less than 135 g/L in men and 120 g/L in women, on the basis of blood
testing. It is not a single disease, but rather an effect from one or more of a number of processes. Anemia
is bad because it can cause fatigue and breathlessness, and can cause heart damage. Patients with major
illnesses who also have anemia tend to do worse than those without anemia.
2. How can you tell if I have anemia
You may feel very tired or weak, feel your heart beating faster, and feel breathless or cold. Your nails may
lose their natural pinkness, and your mucous membranes (especially the inner part of your lower eyelid) may
look very pale. Most commonly anemia is detected by blood testing, before and after your transplant. Usually
the compete blood count (CBC) in a lavender-top blood tube is checked regularly, but sometimes blood iron
stores, folate and vitamin B12 are also ordered.
3. Why do I have anemia
Almost all patients with chronic kidney disease have anemia, because a hormone called
erythropoietin normally made by the kidneys which tells the bone marrow to make
blood, is no longer produced. If your kidney transplant also does not make enough of
this hormone you may have anemia. Unfortunately some of your anti-rejection drugs
and blood pressure lowering drugs which you need can also contribute. You may be
deficient in essential nutrients like iron, folic acid, and vitamin B12. You could also
have an infection which makes it difficult for your body to use these nutrients properly.
Another important cause is blood loss, such as from heavy menstrual bleeding or
bleeding from your stomach or bowels. Sometimes diseases in other organs like the
liver or thyroid can also cause anemia. Rarely, you may be breaking down blood cells
in your bloodstream as a result of certain diseases or drug reactions. Routine blood
testing, even if frequent, is not usually a cause. Anemia is normal and to be expected in
pregnancy. It is usually hard to find a single explanation for anemia.
4. I used to have anemia on dialysis. Will I still have it after my transplant
Some patients continue to have anemia after their transplant due to one or more of the causes listed above.
More commonly however it corrects on its own if the transplant is working well. This may take a few
months.
5. Will fixing anemia solve all my problems
No, unless your symptoms were strictly due to anemia. This is rarely the case. Years of chronic kidney disease
take their toll on the body, so while fixing anemia may solve some aspects of your health situation, it certainly
does not solve everything.
6. Can anemia be improved by diet How about a multivitamin
It certainly helps to eat nutritious food. Your body normally absorbs about 10% of the 10-15 mg of iron present
in a normal diet, and keeps iron balance by losing and absorbing 1 mg per day. Iron rich foods include liver
4

and lean red meats, seafood, various kinds of beans including soybeans, iron-fortified whole grains including
cereals, pasta, and breads, spinach and green leafy vegetables, broccoli, asparagus, and Brussels sprouts. If you
are vegetarian, you do not have to become a meat-eater to get more iron!
Good sources of folic acid include dark green, leafy vegetables, whole wheat bread, beans, peas, nuts and
seeds, sprouts, oranges, liver and other organ meats, and fortified cereals. Vitamin B12 is richly present in
meat and seafood, cheese and eggs. Those who consume no meat or dairy products probably need to take a
supplement. Please check with the transplant clinic before taking any multivitamins.
7. Are there medications which can be used to treat anemia
Sometimes medication becomes necessary. If you are taking an iron supplement, do not stop it without
discussing this at a clinic visit, because your hemoglobin may suddenly “crash”. If you have stomach upset from
an iron tablet, check with our pharmacist who may be able to find another formulation more suited to you. Do
not take iron at the same time as calcium. Do not panic if your stool becomes black with an iron supplement.
Sometimes taking vitamin C along with iron allows it to be absorbed better. Very rarely, intravenous iron
can be given in the hospital. If you have been prescribed folate tablets or vitamin B12 injections, please do not
stop taking them on your own. Rarely, your transplant doctor may decide to change or adjust your transplant
drugs or blood pressure drugs to try to help your body correct the anemia. Finally, you may be asked to take
injections of erythropoietin or darbopoeitin.
8. I have been told to take injections for my anemia. I am nervous about this.
If you took these injections by yourself before the transplant, it will be no different afterwards. If this is your
first time, bring the injection with you back to the transplant clinic as soon as you have filled the prescription
and one of the staff will show you how to inject under the skin. Get a family member involved if needed.
Remember, you can fill your injection only at one pharmacy because it involves special paperwork. Always
keep the syringes stored at the proper temperature so the medication does not get spoiled.
9. Why isn’t my hemoglobin coming back to normal even though I am taking medication for this
Whenever you start an injection or have the dose changed, your hemoglobin should be repeated in 2 weeks.
Often medication adjustment is all that is needed to achieve correction in a few months. Make sure that you
are taking your other medications properly, and are eating a proper diet. If the anemia persists, your doctor
may choose to refer you to another specialist, such as a hematologist or gastroenterologist. Every attempt is
made to avoid blood transfusions. Remember, with injections your target hemoglobin is only 110-120 g/L.
Overcorrecting this into what is the “normal” range for normal people may actually be very harmful.
10. I have been told that my hemoglobin is high.
This is not anemia, is it
This rare but we do see this. It is called erythrocytosis. The
hemoglobin may go up to as high as 200 g/L. No one knows
for sure why this happens but it may be related in some way
to the transplant drugs. If this is the case, you may have to
come to the clinic so that some blood can be removed (it is
useless for donation purposes). Some blood pressure drugs
like ACE inhibitors or angiotensin II receptor anatagonists,
which can sometimes contribute to anemia, may actually
be very useful in this situation.
5

Smoking and kidney transplantation: Don’t let your kidney go up in smoke!
Csaba Ambrus, M.D., Ph.D
Cigarette smoking is an addiction
that affects many people worldwide.
Unfortunately, many patients with
advanced kidney disease or already on
dialysis and awaiting kidney transplant
are smokers as well as a significant
proportion, around 20% of kidney
transplant recipients smoke regularly.
The relationships of smoking with
hypertension, cardiovascular disease and
cancer are well known in the general
population. Because of this evidence,
smoking is usually highly discouraged by
every health professional.
If you happen to be a smoker who is
awaiting a kidney transplant or already
a lucky recipient with a working graft,
or even if you are not affected but just
curious, you might want to know: Are
there any special considerations with
cigarette smoking in kidney transplant
patients
Certainly, there are. According to a study
of 4000 kidney recipients in the US,
patients who smoked cigarettes had a
51% increased relative risk of graft failure,
a 45% increased risk of mortality, and a
24% increased risk of acute rejection
compared to non-smoker recipients.
Increased risk of cardiovascular
disease and death
You might have heard about it, that if
you have severe kidney insufficiency
or are already on dialysis, your risk of
cardiovascular disease is much higher
(even 10-50-fold higher!) compared to
others without kidney disease. Although
somewhat less, your risk is still high as
a kidney transplant recipient. There is
no doubt about the association between
smoking and cardiovascular events in the
general population. This relationship is
more pronounced in kidney transplant
recipients and the already very high
risk of any cardiac or cerebral event is
amplified by smoking. A study of elderly
kidney recipients in Quebec showed that
smoking was the greatest modifiable risk
factor of death after transplantation.
These findings were later confirmed for
younger recipients as well. The likelihood
of an acute cardiac event within the
first two years after transplantation was
3.5-fold higher in smokers compared to
non-smokers. Not only cardiac events but
also peripheral vascular disease is more
common and more severe in smokers.
Increased the risk of early rejection
If you are a smoker awaiting
transplantation, unfortunately, your
risk of acute rejection early after
transplantation is higher. Smokers had
poor early transplant function and
worse graft function one year after
transplantation. The mechanism how
smoking impacts the risk of acute
rejection is not clear, but a few studies
suggest that it might directly affect the
immune system leading to rejection.
Smoking accelerates loss of graft
function
It has been shown that smoking is a risk
factor of worsening renal function in
different renal diseases, such as diabetes,
lupus, IgA nephropathy or polycystic
kidney disease. After transplantation,
smoking is a risk factor for progressive
loss of graft function regardless of your
original kidney disease. According to
an earlier study, patients who smoked
before transplantation had 2.3 fold
higher risk of losing the kidney graft
compared to non-smokers. In another
report, patients who were smokers at the
time of transplantation had inferior graft
survival rates to patients who were nonsmokers:
65% at 5 years and only 48% at
10 years had functioning graft whereas
those numbers were 78% and 62% in
non-smokers, respectively.
“patients who smoked cigarettes had a 51%
increased relative risk of graft failure, a 45%
increased risk of mortality, and a 24%
increased risk of acute rejection compared
to non-smoker recipients”
The good news is that there seems to
be a benefit to quitting, since patients
who no longer smoke at the time of
transplantation do better than current
smokers: an earlier study showed that
patients who quit smoking were not at
higher risk of transplant loss compared
to whose who never smoked. I should
mention that donors’ smoking history
also may affect graft function and
survival.
How does smoking affect the
kidney
Graft loss over the long term is a result
of chronic changes in the kidney due to
both immunological and non-immune
factors. Those processes partly lead to
changes of the blood vessels, resulting
in stiffer and narrower blood vessels in
the transplanted kidney. Similar damage
to the blood vessels is caused by smoking
and it clearly accelerates the process
and contributes to the earlier decline of
graft function. In addition, many other
structures in the kidney changes in
regular smokers.
There are several other mechanisms
underlying the adverse effects of smoking
and the mechanisms are not yet fully
understood. More than 4000 chemicals
have been identified in smoke in the form
of particles or gases; many of those can
accumulate in the kidney (such as lead,
cadmium, mercury, and silica) and those
are toxic even in small quantities.
In addition, nicotine has a great effect on
the circulation increasing blood pressure
and the resistance of peripheral blood
vessels. It also has the ability to blunt the
beneficial effect of certain blood pressure
medication, even in the very short term
after smoking only one cigarette. The
blood flow inside the kidney is also
greatly impacted by nicotine, letting it
exposed to higher blood pressure and
blood flow that can be detrimental over
the long term.
Increased risk of malignancy,
infection and other consequences
Cancer is a well known complication of
transplantation, the risk of malignancy is
3-5 fold higher compared to the general
population and cancers are usually
6

more aggressive. Age, sun exposure and
smoking history are the most important
predictors of cancer development. Various
cancer types have been associated with
smoking after transplantation, especially
lung and lip cancer.
Smoking will damage lung structure
and also inhibit the natural clearance
mechanisms of the airways. As a
consequence, it puts you at greater
risk for lung infections, bronchitis and
pneumonia. Smoking also increases the
acid production in your stomach and
this will delay the healing any ulcers
you may develop. It also impairs the
ability of red cells to carry oxygen, so
less oxygen will reach the tissues in
the body and this decreases the ability
to heal. All these effects are more
severe if you take immunosuppressive
medications. Furthermore, there are
studies suggesting that smoking is also
a risk factor for development of diabetes
after transplantation.
Is it worth quitting even if someone
has been smoking for many years
We do not have much evidence about the
effect of smoking cessation on kidney
function. However, as studies showed in
the general population, the risk of any
event related to smoking will decrease
after quitting. As I earlier mentioned,
patient who quit few years before
transplantation had better graft function
and their graft last longer compared to
those who continued smoking. So it is
never late to quit!
How can I get help to quit smoking
Weaning from smoking is a difficult
process that needs the cooperation of
both patient and health personal. It
requires regular counselling and often
drug support such as nicotine patch or
other medication. Ask your doctor for
help!
I can give you few tips to help you quit:
• Avoid beverages that contain caffeine!
Caffeine, found in coffee, tea, and many
soft drinks, can stimulate your urge to
smoke again.
• Drink more liquids and eat fruits during
the first three non-smoking days,
provided your kidney function allows
you to do so (!!). Body fluids of smokers
have high concentrations of nicotine; as
these concentrations decrease nicotine
cravings increase. Extra liquid can act
as an alternative to cigarettes and help
nicotine pass out of your body.
• Use deep breathing! When the craving
to smoke strikes, you should take slow,
deep breaths. This will help you relax
long enough to consciously decide not
to smoke. It will also help supply your
brain and the rest of the body with
oxygen. Take in a deep breath with your
mouth wide open, bend at the waist,
and breathe out; repeat two or three
times. Stop if you begin to feel dizzy.
• Take your vitamins! Taking a B vitamin
may help diminish the nervousness and
mood swings that can occur when one
tries to stop smoking. Take vitamin C if
you are unable to eat fruit. Remember
to consult your doctor before taking
vitamins.
• Exercise regularly! An aerobic workout,
such as walking briskly, can improve
lung capacity and vascular tone, and
help prevent depression. Consult with
your doctor or physiotherapist before
beginning any exercise program.
• Join a smoking cessation group! These
groups can be helpful for discussing
feelings and learning from others in the
same situation. Check the Yellow Pages
or your local heart, lung, or cancer
society chapter to find a convenient
group.
It is not easy to give up smoking. You
may become anxious or irritable. You
may develop headaches, nervousness,
dizziness, muscle cramps, fatigue,
sleepiness, increased sweating, as well as
difficulty focusing your attention, a loss
of appetite, increased craving for food, or
an intense craving to smoke. However,
if you stick to your decision not to
smoke, you will be breaking a habit that
is harming your health and, in time, the
“withdrawal” symptoms will diminish
and you’ll feel better than ever before.
Your ability to choose not to smoke grows
stronger each time you repeat the choice.
Instead of thinking about how much
you want to smoke, remind yourself
of smoking’s harmful effects and the
health benefits that will be yours without
smoking.
References
1.Tips to quit smoking were taken from the homepage of the Columbia University, with minor modifications and without the author’s permission:
http://www.cumc.columbia.edu/dept/cs/pat/kidneypancreastx/life.html
2.Cosio, F. G., Falkenhain, M. E., Pesavento, T. E., Yim, S., Alamir, a., Henry, M. L., et al. (1999). Patient survival after renal transplantation: II. The impact of
smoking. Clinical transplantation, 13(4), 336-41.
3.Dantal, J., & Pohanka, E. (2007). Malignancies in renal transplantation: an unmet medical need. NDT, 22 Suppl 1, i4-10.
4.Gallagher, M. P., Kelly, P. J., Jardine, M., Perkovic, V., Cass, A., Craig, J. C., et al. (2010). Long-term cancer risk of immunosuppressive regimens after kidney
transplantation. JASN, 21(5), 852-8.
5.Kasiske, B. L., & Klinger, D. (2000). Cigarette smoking in renal transplant recipients. JASN, 11(4), 753-9.
6.Nogueira, J. M., Haririan, A., Jacobs, S. C., Cooper, M., & Weir, M. R. (2010). Cigarette smoking, kidney function, and mortality after live donor kidney
transplant. AJKD, 55(5), 907-15.
7.Orth, S. R., & Hallan, S. I. (2008). Smoking: a risk factor for progression of chronic kidney disease and for cardiovascular morbidity and mortality in renal
patients--absence of evidence or evidence of absence CJASN, 3(1), 226-36.
8.Sezer, S., Bilgic, a., Uyar, M., Arat, Z., Ozdemir, F. N., Haberal, M., et al. (2006). Risk factors for development of posttransplant diabetes mellitus in renal
transplant recipients. Transplantation proceedings, 38(2), 529-32.
9.Sung, R. S., Althoen, M., Howell, T. a., Ojo, a. O., & Merion, R. M. (2001). Excess risk of renal allograft loss associated with cigarette smoking.
Transplantation, 71(12), 1752-7.
10.van Leeuwen, M. T., Grulich, A. E., McDonald, S. P., McCredie, M. R., Amin, J., Stewart, J. H., et al. (2009). Immunosuppression and other risk factors for
lip cancer after kidney transplantation. Cancer epidemiology, biomarkers & prevention, 18(2), 561-9.
11.van Walraven, C., Austin, P. C., & Knoll, G. (2010). Predicting potential survival benefit of renal transplantation in patients with chronic kidney disease.
CMAJ, 182(7), 666-72.
12.Yavuz, a., Tuncer, M., Gürkan, a., Demirbas, a., Süleymanlar, G., Ersoy, F., et al. (2004). Cigarette smoking in renal transplant recipients. Transplantation
proceedings, 36(1), 108-10.
7

Coping With Chronic Renal Allograft Failure
Carmen Morris, MSW DCCP/Nephrology
Allograft failure often causes distress for patients for
whom kidney transplant represented a source of hope.
While explanation for this distress vary from person
to person. The processes used to talk about loss,
bereavement, grief, and mourning, may be used account
for your emotional reactions to allograft failure.
Bereavement is the state where a person experiences
feelings of sadness and loneliness after having suffered
a loss that is either physical or symbolic. From this
perspective, you experience sadness not only because you
have lost the kidney, but also because of the unfulfilled
dreams and wishes you have associated with having a
successful transplant. The length of time for bereavement
varies from person to person.
Grief is the normal reaction to loss that may manifests
itself in physical, social, or emotional forms. Physical
reactions may include changes in sleep or appetite,
and tiredness. Emotional reactions may include anger,
guilt, and anxiety. Social reactions may include both
positive and negative feelings about roles in the family
or employment. As with bereavement, your grief will
depend on the situation surrounding the loss of the
allograft.
Mourning is the conscious or unconscious cultural
reaction to a loss. It is the ongoing process of incorporating
the loss into your ongoing life and is influenced by customs
and rituals and by society’s guidelines for coping with loss.
You may experience mourning in three phases, shock
and disbelief that the kidney is failing, disorganization
and sadness, and followed by reorganization.
Tips for Coping with Chronic Allograft Failure
The stage of reorganization is difficult to achieve at times.
You may find that you are still having difficulty coping
on your own; as your emotions may result in feelings
of more distress. Take steps to find coping support. You
may find ‘grief work’ helpful, by way of easing emotional
distress. Patients report that it enhances their ability to
move beyond the news of chronic graft failure.
‘Grief work’ entails a series of steps you need to finish to
enable you to overcome your loss. These steps include
the process of accepting your losses, experiencing your
pain, adjusting to your new situation, and ultimately
reinvesting your emotional energy into the process of
moving forward. Successful ‘grief work’ require you to
‘engage’ with a caring health professional, who is there to
guide you through the number of steps, and reassure you
that your emotions are natural coping reactions.
In addition, initiate talks with your medical team about
what your treatment options are for the future. The
possibility of another transplant is often a source of
hope and optimism for patients. The fact is; a failed
transplant does not necessarily preclude you from having
a successful transplant in the future.
Finally, strengthen your support system, and seek help to
access community resources. There is evidence to suggest
that you will begin to feel that you have regained control
over your life and better able to transition successfully
to possible dialysis or re-transplantation; with the right
supports in place.
Cited From:
Clara D Neyhart, The patient with progressive renal
insufficiency and a failing transplant, Nephrology
Nursing Journal (June, 2002);
Gill, Paul, Lowes, Lesley, Kidney Transplant Failure
experience: a Longitudinal Study, Nephrology Nursing
Journal, (June, 2002);
“Bereavement, Mourning, and Grief”, the National
Cancer Institute (June, 2010).
8

An Introduction to Diabetes and Kidney Transplant
Tess Montada-Atin, NP MN CDE
Approximately 1.8 million adult Canadians are living with diabetes mellitus. The Canadian Diabetes Association defines
diabetes as a metabolic disorder characterized by high blood sugar due to a problem with insulin secretion, insulin
action or both. Diabetes is associated with complications affecting various organs in the body-particularly the kidneys,
eyes, nerves, heart and blood vessels to the feet and brain.
About 50% of people with diabetes have chronic kidney disease (CKD). CKD is when the
kidneys are damaged and are unable to function properly. Diabetes is the one of the leading
causes of CKD. When kidney disease worsens, it may eventually lead to kidney failure
requiring dialysis or transplant to maintain life.
Blood Sugar control and Kidney Failure
It may become difficult to control blood sugars when the kidneys fail to work properly especially when taking insulin
or diabetes pills. Insulin and some diabetes pills are normally metabolized or broken down by the kidney. However,
when the kidneys are no longer working, the action of insulin is much longer because of the kidney’s inability to
properly break it down. This also happens with certain diabetes pills, which can result in higher than normal levels of
the medication in the blood. This can increase one’s risk for hypoglycemia or low blood sugar. Therefore, when kidney
failure occurs, a significant reduction in the dose of insulin or diabetes pills is often necessary to avoid low blood sugar.
As a result, sometimes people with diabetes and kidney failure can manage their blood sugars without any medication.
This can be misleading as people may believe their diabetes has been cured.
Blood Sugar control and Kidney Transplant
Controlling blood sugars after kidney transplant in someone with diabetes can also be challenging for a few reasons.
Firstly, some of the usual transplant medications raise blood sugar levels, namely, prednisone, tacrolimus, cyclosporine
and possibly sirolimus. Secondly, a healthy transplanted kidney is now able to metabolize or break down insulin and
diabetes pills normally. Therefore, the requirements of these medications to control blood sugar often are much more
than before transplant. Also, the physical stress of surgery can cause high blood sugars particularly in persons with
diabetes. Improved appetite and weight gain following kidney transplantation may also contribute to higher blood
sugars.
Diabetes Management after Kidney Transplant
Close monitoring of blood sugar is very important after kidney transplant. Blood sugar is routinely
checked with other lab tests. Also, self-monitoring of blood sugar at home is encouraged
especially if taking insulin or diabetes pills. Monitoring blood sugar informs us if changes
to the diabetes regimen are necessary. High blood sugars can lead to dehydration if not
treated appropriately. Dehydration can be stressful to the new transplanted kidney.
The targets for good blood sugar control are:
• Fasting blood sugar and before meals: 4-7 mmol/L
• Blood sugar 2 hours after a meal: 5-10 mmol/L
It is not uncommon for a person with diabetes on diabetes pills to require insulin
therapy to control blood sugars after kidney transplant, especially when receiving
high doses of prednisone. Insulin therapy may be temporary in some cases, and
sometimes is needed indefinitely to keep blood sugars well controlled.
Following a healthy diet after transplant is part of the overall management of
diabetes. A registered dietitian can help with this.
Lastly, incorporating regular exercise is important for diabetes management as it helps to lower blood sugar, promotes
weight loss and improves overall health, including heart health.
9

ADVAgraf: A Once-Daily Alternative to PROgraf
Helen Fanous Pharm.D, Rph
Pharmacist - Kidney Transplant
What is Tacrolimus Extended Release (ADVAgraf)
In April of 2008, a new drug, Tacrolimus Extended Release (ADVAgraf) became available on the market in Canada.
ADVAgraf is an anti-rejection medication that helps your body accept your transplanted kidney. ADVAgraf is used in
kidney transplant patients in combination with Mycophenolate (CellCept®/Myfortic) and steroids to protect against
kidney rejection.
What is the difference between Tacrolimus Immediate Release (PROgraf) and Tacrolimus Extended Release
(ADVAgraf)
Both PROgraf and ADVAgraf are approved as anti-rejection drugs for kidney transplant patients and contain the same
active ingredient, Tacrolimus. However, they are released in the body a different ways. PROgraf is an immediate-release
formulation to be taken every 12 hours when used for the prevention of organ rejection, whereas ADVAgraf is an
extended release formulation that is to be taken every 24 hours.
What is the advantage to giving ADVAgraf
Formulating a drug as extended release allows a once daily dosing regimen instead of the twice daily regimen required
with PROgraf for kidney transplant recipients. This can increase adherence to your transplant medications by
simplifying your medication regimen.
Are PROgraf and ADVAgraf Interchangeable
No. Both medications require careful monitoring by you transplant team. Unsupervised switching of PROgraf
and ADVAgraf can lead to kidney rejection or increased risk of toxicity and adverse side effects. Alterations in your
medication regimen should only take place under the close supervision of your transplant team.
When is the best time to take ADVAgraf
You must take ADVAgraf at the same time every day, in the morning. This ensures that the medication is absorbed
adequately and your body has the protection it needs. ADVAgraf can be taken with or without food, as long as you
stay consistent with your preference. Your dosage is to be determined by your transplant team and may change, so it is
important to always be aware of how much you are taking.
What are the side effects of ADVAgraf Are they different from PROgraf
Common side effects of ADVAgraf may include headache, increased blood pressure, tremors, and increased blood sugar.
These side effects are comparable to those experienced with PROgraf. It is important to note that side effects can vary
from person to person. If you experience any of these effects, be sure to report it to your transplant team.
Are there any drug interactions associated with ADVAgraf
ADVAgraf is associated with both food and drug interactions. Avoid grapefruit juice as this can increase the blood
levels of the drug in your body. Always discuss with the transplant team before starting any new medications - either
prescribed or over the counter.
There are several dosage strengths for ADVAgraf. Ask your pharmacist if you notice a change in appearance of your pills.
Strength
Covered by Ontario
Drug Benefit/Trillium
0.5 mg
1 mg
3 mg N/A
5 mg
10

NOTES

Funding for this publication provided by Hoffmann-La Roche Limited