Transplant Digest Fall 2018/Winter 2019, Issue No. 25
Importance of the Pre Transplant Assessment Dr. Ramesh Prasad Every patient with chronic kidney disease being considered for a kidney transplant needs to have a pre-transplant assessment. If you are considering a transplant, then you will need to be seen by a nephrologist, surgeon (typically a urologist) and anesthesiologist. This whole process can be long and frustrating. It may take a few months to get these appointments. The appointments have to be scheduled around dialysis and other commitments, and sometimes even are on separate days. But why are these clinic appointments so important? The first purpose of the pre-transplant assessment is to make sure that you are an appropriate candidate both medically and surgically. It is critical to determine if the transplant will not cause you more harm than good. Conditions like cancer, severe heart disease, and chronic infections can become much worse after a transplant. The physical examination you undergo in the clinic and a review of all your test results up to that point are very important. It is also important to make sure that you are likely to take proper care of your transplant. The second reason is to provide education. The more you and your loved ones know about the transplant process, the more likely the transplant is going to be successful. A lot of information is shared, and you can bring as many people as you like to the appointment. The more people are engaged in the process, the better! The middle of the night, when you are called in for the transplant, is not the time to begin the education process.
In this issue... Importance of the Pre-Transplant Assessment From the Editor’s Desk Contact Information Chronic Antibody-Mediated Rejection Pneumocystic jirovecii Pneumonia The Molecular Revolution in the Microbiology Laboratory Cardiac Magnetic Resonance Imaging Study Completed! Post-Transplant Chat: Exercise Summer Experience at St. Michael’s Hospital Transplant Clinic International Transplant Nurse Society Conference in Germany Helping you stick to your medicines: a new pilot program at the clinic
The third reason is to outline specific risks and benefits of the transplant in your case. A particular medication strategy, or additional tests, may be required to make sure you can go on the list. Please consider the transplant listing as a “work in progress”, something to aspire towards, rather than just a simple “yes” or “no” on the appointment day. The next reason for the assessment is to improve your health. There are perhaps no other assessments in medicine that are so thorough. Sometimes new medical Continued on page 9
Transplant Digest Fall 2018/Winter 2019, Issue No.125
From the Editor’s Desk Welcome to the Fall 2018 issue of Transplant Digest. Our moods change when the days get short, the temperature gets cooler, and the leaves change color. We begin looking forward to the Holiday Season and the New Year. We may try new activities, or look at old things in our lives in new ways. An important underlying constant, however, is your transplant kidney and its health. Daily medications, regular blood testing, and clinic visits don’t change with the season. That’s why we have always had at least one Transplant Clinic every week, every year. We can never be closed for too long. We are fortunate to have some non-transplant nephrologists skilled enough in transplant medicine to help us out in this regard. In this issue of the Digest, we cover many important aspects of your health. We have in-depth articles on medication adherence, molecular diagnostics, post-transplant pneumonia, pre-transplant assessments, and antibody-mediated rejection. Our ever-popular Post-Transplant Chat WELCOME discusses the topic of exercise. We also have an FALL... article written by one of our summer students, and our Chief News Correspondent, Galo Meliton, who recently took Berlin by storm with his presentation on ABO incompatible transplantation. A Transplant Word Search will hopefully provide some entertainment while you wait for your appointment. Until next time, here’s wishing health and happiness to you and yours. Dr. Ramesh Prasad, Editor
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. For all questions related to your own health please contact your health care provider.
Contact Information Dr. Ramesh Prasad – Editor Meriam Jayoma-Austria, RN, BScN, CNeph(C) – Newsletter Coordinator 2
Chronic Antibody-Mediated Rejection Dr. Jeffrey Zaltzman Over the last 50 years there has been tremendous progress made in the success of kidney transplantation. In 1970 there was only a 40% chance that a patient receiving a kidney transplant would either be alive or free from dialysis at one year. Owing to improvements in the anti-rejection medications, and better treatment of infections, the current one-year kidney graft survival rate is now between 90 to 95%. However, long-term allograft ( kidney transplant) survival has not improved to the same degree. On average, a kidney from a deceased donor lasts about 10 to 12 years, while a kidney from a living donor, on average is expected to last 15 to 20 years. While there are many reasons that transplanted kidneys slowly fail over time, the single largest cause relates to an entity known as chronic antibody mediated rejection. The drugs that are used to prevent rejection also known as immunosuppressants, primarily act by suppression of a part of the immune system mediated by T lymphocytes. This is part of the immune system is an important component, and successful inhibition of T lymphocytes has resulted in the success of transplant that we see today. In general, patients are taking 1 to 3 different antirejection medications to suppress T lymphocytes. However, there are other important components of the immune system that play a role in kidney transplant rejection. B lymphocytes are the cells that produce antibodies. Antibodies are proteins that detect foreign Invaders. An example of an antibody response familiar to most is what happens after getting a vaccination. A vaccination uses a low dose, or non-infectious dose of the pathogen and when the B-lymphocytes recognize this infection, specific antibodies are made by the B-lymphocyte family of cells. If someone is exposed to the true infection, then the antibody system is revved up to prevent or reduce the consequences of the infection. The current anti-rejection medications are much less effective in dealing
with B-lymphocytes and antibodies.Unfortunately transplant recipients can produce antibodies against their new kidney. These antibodies are known as Donor Specific Antibodies or DSA. About 20% of kidney transplant recipients will develop DSA at some time after transplant. Even though the anti-rejection drugs are not very effective in treating B-lymphocytes , patients at highest risk of developing DSA are those who are not adherent to with their anti-rejection medication: Missing doses, wrong timing of dosing, or unsupervised reduction or stopping of anti-rejection drugs. These practices can lead to acute rejection (a rapid deterioration of kidney function), or a more slow process of kidney deterioration - chronic antibody mediated rejection. Often such patients will have detectable de-novo (new) DSA in their blood, and lab findings of increasing protein loss in their urine (High ACR), and increasing serum creatinine (deterioration of kidney function). Sometimes DSA and subsequent chronic antibody mediated rejection can occur in kidney transplant patients who are 100% adherent to their anti-rejection medication regime. Chronic antibody mediated rejection is the single largest reasons why kidney transplants fail. At present there is no specific therapy to deal with chronic antibody mediated rejection. The goals of slowing kidney function deterioration are to safely maximize the current immunosuppressive medications and try to achieve excellent blood pressure control, which often includes using classes of medications known as ARBs and ACE inhibitors. There are a number of experimental agents that are being examined. One such class of therapies target a protein known as IL-6. Early data suggests that these may have some efficacy in reducing the rate of kidney transplant deterioration. Over the next year, the transplant program at St. Michael’s will likely be involved in a large global trial to test the efficacy of one of the IL-6 inhibitors.
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Pneumocystic jirovecii Pneumonia Dr. Ramesh Prasad Pneumocystis jirovecii Pneumonia, or PJP, was first described in the lungs of rats in 1909 and in humans in 1942. PJP may be more familiar to some readers as Pneumocystis carinii Pneumonia, or PCP, which is its former name. PJP is an important infection in kidney transplant recipients. Therefore, all transplant programs take steps towards preventing this infection in their patients. The risk of PJP infection is highest between two and six months after the kidney transplant, because this is the time period when the immune system is most depressed. Without any preventive medication, infection can occur in up to 14% of patients. Everyone is exposed to the organism from the environment. PJP can occur through both as a result of reactivation of the organism already present inside the body, or from a new infection through person-to-person transmission. Infection by more than one strain of Pneumocystis jirovecii is possible. Immunodeficiency or immunosuppression is a required for infection. PJP is well known in patients infected with HIV, for example. However, unlike in HIV-infected patients, an acute lung infection is much more common in transplant patients. PJP is potentially quite serious. Patients who develop PJP are often admitted to the hospital, and sometimes need to be placed on a ventilator. Fortunately, PJP can usually be prevented. Trimethoprim-sulfamethoxazole (TMPSMX), or septraÂŽ is a drug first introduced in 1968. TMP-SMX reduces the risk for
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non-HIV related PJP by over 90%. Therefore, TMP-SMX is the drug of first choice to prevent PJP in the Transplant Clinic. We prescribe it as one single-strength tablet (containing 80mg trimethoprim and 400 mg sulfamethoxazole) once daily for the first year after transplantation. However, other regimens do exist, and there is no clear consensus about which method is best. Unfortunately, some patients cannot tolerate TMP-SMX. Side effects such as itching and rash, high blood potassium, high liver enzymes, and low white blood cell counts are common. In that situation, the dose of TMP-SMX is typically reduced, for example to one tablet three times per week, or even lower. Sometimes, TMP-SMX needs to be stopped altogether because of a side effect. In that case, we will try to restart it at some point, usually at a lower dose, once the patient has recovered from the side effect. The decision to restart TMPSMX is made based on the overall risk for PJP weighed against the severity of the side effect. Another approach is to start another medication instead of TMP-SMX to prevent PJP. Examples of such medications include dapsone, atovaquone, and pentamidine. Your doctor may consider these options for you, and discuss them in the Transplant Clinic as well. If you have any questions about PJP prevention, you can also discuss them with our pharmacist. PJP is an important post-transplant problem to prevent.
The Molecular Revolution in the Microbiology Laboratory clinicians will monitor closely for the presence of BK Karel Boissinot and Ramzi Fattouh When it comes to microbiology and infectious diseases, an increasing number of laboratory tests are shifting over to the realm of ‘molecular diagnostics’. But what does that actually mean and why is that happening? Read on to find out!
What are molecular diagnostics? In the broadest sense, ‘molecular diagnostics’ really just refers to a collection of test methods that seek to answer a particular question by investigating at the molecular level, e.g. proteins or DNA. In microbiology and infectious diseases, molecular testing usually involves looking for the presence of a microorganism’s genes (i.e. their DNA or RNA). The most common molecular approach used today to look for the presence of microorganisms is a procedure known as PCR (Polymerase Chain Reaction). PCR is a method that can be used to multiply a small amount of DNA into trillions of copies (or more) of DNA. Imagine trying to find a needle (i.e. a particular microorganism) in a haystack (i.e. a sample of blood), not an easy task, but if you have a method of multiplying that needle a trillion times within that same haystack, then it becomes much easier to find it. That’s the power of PCR!
Of what use are molecular tests, such as PCR, for transplant patients? For our patients with kidney transplants, one microorganism of particular concern is known as BK virus. Interestingly, this virus was first identified from the urine of a kidney transplant patient and was named after that patient’s initials B.K. BK virus infects nearly everyone by their teenage years, the infection is life-long, but BK virus rarely causes disease in people with healthy immune systems. However, immunosuppression following kidney transplantation may permit the virus to escape immune control, increasing the risk of kidney failure. This is why
post-transplantation. The most common approach used by the microbiology laboratory today to look for the presence of BK virus is a BK-specific PCR test. If BK virus is present in a sample then by using PCR the microbiology laboratory will be able to detect this from a blood sample. Importantly, amplification (or “ramping up”) of DNA by PCR requires some starting material. Just like with a photocopier, you need an ‘original’ in order to make copies. So, if BK (or any other microorganism of interest) was not present in the sample then amplification would not occur and the laboratory report would indicate that BK virus was ‘not detected’. Other viruses like CMV (Cytomegalovirus) are also of concern post-transplantation and like BK can be monitored using a PCR test.
What are the advantages of molecular tests? Previous tests that were used to detect BK virus were laborious to perform and often took weeks to complete. In contrast, molecular tests such as PCR can provide definitive results in as little as one working day. In addition, PCR is very sensitive and is able to detect the virus even when only a few copies are present. Furthermore, with the development of standardized controls, the laboratory is not only able to detect the presence of BK but also tell how much virus is present, thus informing whether levels of the virus are changing over time in response to changes in immunosuppression. As the molecular revolution continues and DNA-sequencing methods come online, even more information will become available, such as factors making the virus more virulent and causing drug resistance. These advances may further improve patient care following organ transplantation. 5
Cardiac Magnetic Resonance Imaging Study Completed! Dr. Ramesh Prasad Thank you to all those kidney transplant candidates and recipients who participated in the Cardiac Magnetic Resonance Imaging (CMR) study. This study was funded by the Heart and Stroke Foundation of Canada, and was performed at St. Michael’s in collaboration with University Health Network and the London Health Sciences Centre. About 80 subjects took part; half of the patients had living donor transplants, and the other half were waiting for a transplant on the deceased donor transplant waiting list. All the subjects had a CMR study performed soon after enrolment, and those who had a living donor transplant had a second CMR performed 12 months after the transplant. Those waiting for a deceased donor transplant had their second CMR 12 months later, while still on dialysis. Some blood biomarkers indicating heart function and disease risk were measured at baseline, and again 3 and 12 months later. Our study found that the volume of blood inside the heart during the various parts of its beat, called the left ventricular end-systolic volume and left ventricular end-diastolic volume, improved after kidney transplantation. The blood concentrations of two
WORD SEARCH Bloodwork Gift Type Give Catheter Immunity Urine List Clinic Nurse Virus Rejection Cut Stent Wait Steroid Diarrhea Surgeon Donation Tacrolimus Drug Transplant
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hormones, adiponectin and B-natriuretic peptide, also improved (lowered) after transplantation. Furthermore, these two hormones correlated with each other only after a transplant, indicating that hormones that affect heart growth and function work properly with each other only in the presence of proper kidney function. The study was accepted for publication in the Canadian Journal of Kidney Health and Disease. Patients with kidney disease are at high risk for heart disease. This study sheds some light on the mechanism by which the risk for heart disease improves after a kidney transplant. We sincerely appreciate the effort all of our patients contributed to better understanding how kidney disease and heart disease are related to each other. With the knowledge gained from this study, and future studies, we may be able to identify patients with kidney failure who are at especially high risk for heart disease, and target them with more medication or other therapy to help reduce that risk.
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Post-Transplant Chat: Exercise Jennie Huckle, RN; Fernanda Shamy, RN, Galo Meliton, RN; Kevin Bradley, RN; Kathryn Salvatore and Sarah Mattok, RN 1. I’ve been told exercise is good for you. Is this true for kidney transplant recipients? Exercise is good for everyone including kidney transplant recipients. Exercise has positive effects in helping to fight many diseases and can actually extend life. 2. I have a fresh wound from the transplant. Can I still exercise? Yes, you can. Exercise is possible even on the first day after your surgery, when you get up out of the bed and into a chair for the first time. You were/will be encouraged to walk, with assistance of course, for a short distance on the ward. You will be asked to continue to walk daily, and increase your walking distance each day. You will also be asked to increase your overall exercise and activity each time. 3. What kind of exercise is safe in the first three months after the transplant? How about after this? There are many simple exercises you can do every day as you continue to recover. Walking, simple stretching, climbing stairs, and simple squats are examples of some exercises you can do. Please ask about these at your Transplant Clinic visit. We may even be able to demonstrate some of these for you. However, you should NOT lift more than 10 pounds at a time in the first three months. 4. I feel too weak to exercise. What could be the reasons? Chronic kidney disease, plus the stress of surgery may have tired you out. Your energy should increase as time passes, and you will be ready to start simple exercises. Medical causes for extended weakness include anemia, poor kidney transplant function, and infections. If you did not exercise regularly before the transplant, you may find it harder after the transplant because you are deconditioned. 5. I don’t feel like exercising even though the clinic says I should. Do I still have to exercise? What are the benefits? Yes, you still have to exercise! Your circulation will improve so your whole body receives more oxygen. You will feel less short of breath as your lung capacity improves. Your endurance increases, Your blood pressure will be lower. Your muscle tone, strength, balance, and flexibility all improve. Your bones will be stronger. Your body fat reduces and you will reach and maintain a healthy weight. Sleep will be better. Your diabetes control will improve, or you may even avoid diabetes. Best of all, your self-image and self-esteem will improve! 6. When can I use an exercise bike? How about a treadmill? About 4-6 weeks after the transplant, once your stent is out and your incision is completely healed, and you can walk normally, you can then start an exercise bike. At that time, you can also walk on a treadmill at a basic level, and increase the time as you gain confidence. 7. Can I play contact sports? It is best you do not play contact sports, due to the kidney being in front and superficial, and therefore prone to injury. If you feel you must play contact sports, please speak about your wish in the Transplant Clinic. 8. How much weight can I safely lift? Am I allowed to build muscle? Do not lift over 10 pounds in the first three months. This is equivalent to a gallon of milk, a holiday ham or turkey, filled large garbage bag or a laundry basket filled with towels or jeans. After three months, based on your progress, you can lift more. Please ask in the Transplant Clinic for more specific guidance in this regard. 9. Are there any benefits to the kidney transplant itself from exercise? Kidney transplant recipients who exercise will live better and live longer than those who do not exercise. A healthy body supports a healthy transplant, just as a healthy transplant promotes health in the rest of the body. It’s as simple as that! Do not be skeptical. 10. Can you recommend any specific exercise programs for me? The best exercise is one you enjoy and can do regularly. Any physical activity that uses energy counts as exercise. Your local gym can direct you to specific programs available in your area.
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Summer Experience at St. Michael’s Hospital Transplant Clinic Michael West I am Michael West and I am going into my third year of medical school at the Royal College of Surgeons in Ireland. I have had the privilege to be a research summer student at the transplant clinic this summer with Dr. Prasad as my principal investigator and Michelle Nash, research manager for the clinic. This has been my first opportunity to be involved in research, and I could not think of a better place than the transplant clinic at St. Michael’s Hospital to start my journey. Dr. Prasad and Michelle have given me great freedom to work on what interests me, which has made my time here all the more enjoyable. I started out the summer by entering data relevant to the study I was working on into a special computer program. As the summer progressed, I continued to do this but was also able to do some writing, which I was very happy to do, as I enjoy writing. This has included a case report, a literature review, and I hope to begin writing up a study very soon. Also, having been a part of the Keenan Research Summer Student program, I was given opportunities to hear about research projects that other summer students are taking part in. Once a week, there were poster presentations, where 2-5 students would give a short presentation on their research project, which it was always interesting to hear about. Also, I was able to attend grand rounds multiple times, which was also very rewarding. I have learned so much this summer, not only about kidney transplantation and related disciplines, but about the research process in general. This includes skills such as extracting relevant information from scientific papers and medical charts, as well as giving me a chance to practice writing in a scientific way. Also, I was able to appreciate how important research is to clinical practice. One aspect of being in the transplant clinic that surprised me was just how much work goes into conducting a study. Aside from the doctors in the clinic who conduct the studies, there are three full-time researchers in the clinic, Michelle, Lindita, and Weiqiu, who all work very hard to run the studies and make sure they go according to plan. It would be remiss of me not to mention and thank all three of them, as they have taught me so much and made my summer so enjoyable. I would also like to thank Drs. Prasad, Zaltzman, and Yuen, who have all allowed me to participate in their studies, and also allowed me to observe their clinics, which was a very valuable experience. Their hard work and dedication has shown me how demanding it is to be a clinician who conducts research, but also how rewarding it can be. I am confident that the skills and knowledge I acquired this summer will serve me well in future research, in my undergraduate studies, and beyond.
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International Transplant Nurse Society Conference in Germany
One of the Kidney Transplant Nurse Coordinators in the post- kidney transplant clinic, Galo Meliton, RN gave an oral presentation on June 29, 2018 at the European Transplant Nursing Symposium presented by the International Transplant Nurses Society (ITNS) held in Berlin, Germany. The theme of the event was Transplant Nursing in a Globalized World. It was attended by transplant nurses and Allied Health professionals from several continents focused on the care of organ transplant recipients be it heart,liver, lung or kidney transplants. Galo’s talk was on the St. Michael’s Hospital‘s experience in regard to the ABO (blood group) incompatible direct kidney transplantation, and the several initiatives this program is involved with moving the program forward. Galo received excellent verbal and written evaluations from the audience.
Pre Transplant Assessment story continued from page 1
conditions are picked up, or old conditions are put into a new perspective. Regardless of the transplant, understanding your other medical conditions better can help to manage those conditions better, and thereby improve your overall health. Finally, some patients who are clearly not candidates for a transplant refuse to take a “no” from their own nephrologist. In that case, we will schedule an appointment to clearly explain why a kidney transplant is not the best approach to take for improving overall health. However, you can be assured that if you have been scheduled for a pre-transplant assessment, then the chances for being accepted for transplant listing are quite good. In the end, a detailed letter goes back to your referring nephrologist. This letter outlines the plan going forward towards listing, and acts as a “roadmap” for all your other health care providers to get your remaining tests and appointments organized. Once these are all complete, you can be listed, or may be asked (rarely) to come back for another assessment in the clinic prior to actual listing. 9
Helping you stick to your medicines: a new pilot program at the clinic Lucy Chen, BScPhm, PharmD In May 2018, the transplant clinic started a new pilot to see how we can help transplant patients adhere to medications better. To “adhere” means to take your anti-rejection medicines, on time, every day, as prescribed by your doctor. We started this pilot program because sticking to a medicine routine every day, year after year, is not easy. If you haven’t always been adhering to your medications, you are not alone. 1 in 3 people with a kidney transplant have trouble with taking medicines regularly. But, we know that people who do not take antirejection medicines regularly are 7 times more likely to reject their transplanted kidney permanently. In fact, sticking to your medication routine is probably the most important thing you can do for the health of your transplanted kidney. Your immune system never adapts to having a foreign organ in your body. Rejection can happen anytime you miss your medicines, even after many years. You may even feel fine despite missing some doses of medication. This doesn’t mean you are safe. Rejection does not always cause symptoms. Sometimes, when people do not take anti-rejection medicines regularly, there may even be no change in blood test results. But, there is always a risk of rejection.
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• Build a routine that works for your life. Make medicationtaking a habit, like brushing your medicine or taking a shower. • Simplify. A simpler routine is easier to remember. Ask your doctor or pharmacist if your prescribed regimen can be made simpler. • If you use a smartphone, try a medication reminder app. (Many are free!) You can keep track of how well you do with medication-taking each month. • If you don’t want to use an app, a daily alarm on your watch or phone can help.
What is the medication adherence pilot program? At each visit, your transplant clinic nurse or pharmacist will ask you questions about how you are taking your medicines, including: 1. What is the name, dose, frequency and timing of each medicine? 2. In the past month, how often have you missed a dose of medicine?
The transplant team is here to help you get better at adhering to your medications. You can meet with the case manager at the clinic to talk about what barriers are stopping you from sticking to your medication routine every day. The case manager will work with you and the rest of the transplant team to find solutions that work for you. The case manager will also check in with you by phone afterwards to make sure the plan is working and you are staying on track.
3. In the past month, how often have you taken your medicine late or early by 2 hours or more?
Here are some tips to help you stick to a medication regimen:
You will have the opportunity to meet with the clinic case manager. The case manager will work together with you to find ways to get better at sticking to your medicine routine.
Be honest. Try to answer as accurately as you can. Our intention is never to embarrass or shame you. Talk to the transplant team if you are having trouble with side effects, paying for medications, memory issues, physical concerns or something else. We want you to get the maximum benefit from your medicines so you can live with a healthy transplant for as long as possible.
FOCUS T H E C A M PA I G N F O R S T. M I C H A E L’ S T R A N S P L A N T AND KIDNEY CARE CENTRE
IMAGINE IF THE WORLD-CLASS CARE YOU R E C E I V E AT S T. M I C H A E L’ S H O S P I TA L C O U L D B E M AT C H E D B Y A N E W S TAT E- O F -T H E- A R T FA C I L I T Y.
THAT ’S THE PLAN. We are launching a $7 million fundraising campaign to build a physical space that provides greater comfort to our patients and enables us to invest in research that will stop kidney disease from impacting any more lives. We have the rare opportunity to build a new facility on the eighth floor. With your support, we will create the centre that our patients deserve. Please join us.
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St. Michael's Transplant Clinic is celebrating 50 years of service in 2019. Stay tuned for the yearlong celebration...