British Columbia Transplant Society Website

History of Kidney Transplantation

Transplantation has become a well-recognized treatment option for people with organ failure. Three major factors have made transplantation a success:

• advances in surgical techniques
• the discovery of anti-rejection medications
• an increasing public awareness for organ donors

Kidney transplantation is the preferred treatment option for most people with end-stage kidney disease. The first kidney transplants were performed between identical twins in the early 1950s without the use of anti-rejection (immunosuppression) medication. It wasn't until 1966 that cadaveric kidney (obtained from someone who has deceased) transplants became a recognized form of treatment. The clinical use of cyclosporine (an immunosuppressive medication) in 1978 revolutionized transplantation with improved graft survival. The discovery and use of cyclosporine marked a new era in transplantation.

The first kidney transplant in BC was performed in 1968. Since then, thousands of British Columbians have received kidneys, thus restoring their quality of life.

How Your Kidney Works

Kidneys function to keep the body in balance (called homeostasis), by controlling the composition and volume of blood. The system accomplishes these functions by removing and restoring selected amounts of water and various solutes, controlling blood acidity (called pH) and excreting selected amounts of wastes. The kidneys also have several hormonal roles, including production of erythropoietin (a substance necessary for the production of hemoglobin), renin (a substance involved in blood pressure control), and activation of vitamin D.

How Kidney Failure Affects Your Health

Kidney failure occurs when the normal functions of the kidney are affected to varying degrees. When kidney failure is mild or moderate, treatment may include drug therapy and dietary changes, but when it is severe, artificial kidney treatment is necessary in order to maintain life. Dialysis is a reasonable treatment option but for some people transplantation may be better.

Success for Kidney Transplantation

Kidney transplantation is excellent therapy for patients with end-stage kidney disease. The one-year graft survival rate is over 90%. . While these patients will require immunosuppresants for the rest of their life, their quality of life is typically excellent.

Click here for patient and graft surival rates

Transplant Assessment

Although transplantation is considered an established treatment for end-stage organ failure, it is not suitable for everyone, so the transplant team must carefully assess every potential transplant patient. The assessment phase starts when your kidney specialist refers you to the transplant team.

As part of the initial assessment, you will have several tests and be interviewed by various team members to determine whether transplantation is the best treatment option for you.
These tests may include:

• bloodwork
• x-rays
• cardiac and vascular studies

You will also receive information that will help you make a decision regarding transplant. The goal of the assessment phase is to find out whether transplant is a safe and reasonable procedure for you, and whether transplantation is right for you.

It is not unusual for additional tests to be ordered to determine your physical ability to undergo surgery and achieve good quality of life. In some instances, arrangements will be made for patients to be seen by additional specialists. The goal is to enable you to be fit for transplant.

Transplant Waiting List

Because of the shortage of cadaveric organs, the waiting period for a cadaveric kidney transplant has increased over the past few years and may be greater than five years. It is very important that you remain as healthy as you can while waiting for a transplant.

In British Columbia, the allocation of kidneys is based on time on the wait list. In addition, priority will be given to:

1) patients who are unable to dialyze;
2) patients under the age of 18; and
3) patients who have a high antibody level and are at high risk for rejection.

All patients on the waiting list are treated equally and evaluated objectively.

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Receiving a Kidney Transplant

When a suitable organ has been found, arrangements are made for you to be admitted to the transplant ward and prepared for surgery. You will need to make your own arrangements to get to the hospital. It is a good idea to have a plan to follow for when the call comes. This plan will include arrangements for children, work, pets, and plants.

Your surgery will take approximately 3 hours. Following surgery, you will be transferred to the post-anesthetic recovery room (PAR). After a few hours you will return to the ward to be cared for by the transplant nurses. The transplant ward nurses and physicians will explain the procedures to you in detail at the time of your admission.

Recovery on the transplant ward

The average stay in hospital is seven to ten days. During your stay, the transplant nurses and other team members will prepare you for going home and caring for yourself. You will be expected to know your medications and to be able to administer them properly. Information will be given to you about follow-up appointments with the transplant doctors and nurses in the Post-transplant Clinic.

Living with a Kidney Transplant

Anti-rejection drugs
Rejection episodes
Infection
Medication and other costs

You must live in the lower mainland (close to Vancouver and VGH/SPH) for approximately three months following surgery so that you can be closely monitored. When you first leave the hospital, you will need to visit the clinic usually twice a week, and sometimes more frequently depending on the care you require. If you are from out of town, this is a major consideration and should be discussed prior to coming to Vancouver for transplant. For many, this involves both financial and emotional hardship. Discussion with your social worker prior to transplantation is key, and your social worker will work with you to establish a plan.

After six months, your clinic visits decrease to once a month, and eventually, to once every three to four months or less. The frequency of your follow-up visits to the clinic depends on your health and progress. This varies for each individual.

Anti-rejection drugs

Acute rejection is a common complication for transplant recipients. It occurs because your body's immune system recognizes your transplanted organ as "foreign" and tries to get rid of it. This process is called rejection. Your immune system is your body's defense against infection and disease. If nothing were done to stop the immune system, it would eventually damage or destroy your new organ.

Successful organ transplantation is now possible because of the use of anti-rejection drugs. To try to prevent your immune system from rejecting your new organ, you will be given immunosuppression or anti-rejection drugs (these two names are interchangeable). The doses of these drugs are carefully measured and monitored so that they prevent rejection, but still allow your immune system to recognize and fight rejection.

With the use of these drugs, your chance for a successful organ transplant is excellent. You will have to take the anti-rejection medications for as long as you have your transplanted organ.

Various immunosuppressive drugs are used in combination. When you first start taking anti-rejection drugs, the doses will be high. After the initial period (the first three to six months), as the risk of acute rejection decreases, the doses will be lowered. Usually by the end of your first year after transplant you are taking a considerably lower dose than in the initial period.

The most commonly used drugs are cyclosporine or tacrolimus, azathioprine or mycophenolate, and prednisone. Each drug works in a slightly different way and has different side effects. By taking two or three drugs together, you can be on lower doses of each drug to minimize their side effects, while maintaining an effective defense against rejection and infection.

After you are transplanted, the nurses and the pharmacists on the ward will teach you about your medications, how and when to take them. Initially, nurses will give the medications. Gradually, before your discharge, you will have the responsibility for taking them yourself.

It is a good idea to record the daily doses of drugs taken, and to bring this record to each clinic visit. The dosage of the anti-rejection drugs are frequently changed in the early phase post-transplant, and many people find it easier to write down the changes to prevent any misunderstanding or medication error.

Commonly prescribed anti-rejection drugs

Cyclosporine or Neoral Cyclosporine
Tacrolimus (Prograf®)
Azathioprine (also known as Imuran®)
Mycophenolate (also known as CellCept®)
Prednisone

Cyclosporine (also known as Neoral®)

Cyclosporine revolutionized transplantation because it was the first drug found to be consistently effective for preventing rejection. This drug modifies certain white blood cells called lymphocytes, which are involved in rejection.

To be effective, the drug must stay at a certain level in your blood. If the level is too low, your transplanted organ may be rejected. If the level is too high, your kidneys or liver may be damaged. Usually, any damage is reversible once the drug returns to its proper level. The level of cyclosporine is measured frequently with a blood test while you are in the hospital, and after discharge during visits to the clinic.

Cyclosporine is available in soft gelatin capsules. The capsules are available in 25 mg (grey), 50 mg (white), and 100 mg (grey). Each capsule is wrapped in foil, and should be kept in the foil until you need a dose. When you are ready to take a dose, remove the number of capsules you need to make up the dose. Swallow the capsules whole. You may take cyclosporine with any drink except grapefruit juice (as grapefruit juice will alter the absorption of cyclosporine) unless your physician instructs you otherwise. It is very important that you take cyclosporine with the same drink every time.

The most common side effects of cyclosporine are listed below. Remember that everyone responds differently to medications, so you may experience only some of the side effects or none at all.

Possible side effects of cyclosporine:

• high blood pressure, and headaches
• increased risk of infection
• mild hand tremors
• fine hair growth on the upper body
• gum tenderness (to prevent problems with your gums, brush and floss your teeth daily, and visit your dentist regularly)
• sensitivity to hot and cold, flushing
• runny nose
• vivid dreams

If you notice any of these side effects, tell a member of your transplant team. They will assess whether you are suffering from side effects of the drug or something else.

Tacrolimus (also known as Prograf® or FK-506)

Tacrolimus is another anti-rejection drug that acts in much the same way as cyclosporine. Tacrolimus is used in some transplant patients in place of cyclosporine (tacrolimus and cyclosporine should not be taken together). Tacrolimus, like cyclosporine, is used with steroids and azathioprine (Imuran®) or MMF (mycophenolate Mofetil) to prevent or treat rejection of the transplant organ.

Tacrolimus is available in 1 mg and 5 mg capsules. The 1 mg capsules are white and oblong with "1 mg" written on the top. The 5 mg capsules are grayish-red and oblong with "5 mg" written on the top.

Like other medications, tacrolimus may cause side effects in some people. If you think you are experiencing side effects, talk to your doctor right away. Do not stop taking tacrolimus on your own.

Possible side effects of tacrolimus (Prograf®):

• headaches
• tremor
• tingling in your hands or feet
• nausea and vomiting
• diarrhea or constipation
• difficulty sleeping
• changes in moods or emotions

Like other anti-rejection medications, try to take your dose at the same time every day. Make sure your doctor, dentist, and pharmacist are aware of all medications you are taking, including anything you buy off the shelf, such as over-the-counter drugs and herbal or home remedies. Taking antacids at the same time as tacrolimus, for example, may affect the way tacrolimus works for you, so these drugs should not be taken together.

Some patients may experience side effects not listed above. If any side effect becomes bothersome or won't go away, contact your doctor, transplant clinic, or pharmacist.

Azathioprine (also known as Imuran®)

Azathioprine is also used to prevent rejection. The use of Imuran has changed recently, to be incorporated into your transplant medication regime in the 2nd year of your transplanted kidney. Mycophenolate (described in the next paragraph, has been proven to be more effective for the first year). This drug suppresses the production of certain white blood cells, which are active in the process of rejection. The drug also suppresses the production of cells that are important in fighting infection. A complete count of blood cells (by a blood test) is done daily while you are in the hospital, and regularly at the clinic once you are discharged. The dosage of azathioprine is adjusted to keep the blood counts within safe limits.

Azathioprine is very well tolerated and most people are not really aware of any problem while on this medication. However, like any drug, side effects are always possible. The most common side effects of azathioprine are listed below. Remember that everyone responds differently to medications, so you may experience only some of these side effects or none at all.

Possible side effects of azathioprine:

• nausea and vomiting
• loss of appetite
• skin rash
• muscle/joint pain
• infection

If you notice any of these side effects, tell a member of your transplant team. They will make sure the problem is a side effect of the drug, and not a sign of rejection of your transplant, or another medical problem.

Azathioprine is available in both intravenous solution and oral tablet form. It comes in 50 mg tablets, which can be broken for smaller doses.

Mycophenolate (also known as CellCept®)

Mycophenolate is an anti-rejection drug that works in much the same way as azathioprine (Imuran®). Recently, Mycophenolate has been incorporated into the kidney transplant medication regime for use in the first year of your transplanted graft. It has been proven to be very effective in preventing acute rejection during this first year. Some transplant patients take mycophenolate instead of azathioprine. Mycophenolate is used with either cyclosporine or tacrolimus, and steroids to prevent or treat rejection of the transplanted organ.

Mycophenolate is available in blue/brown gelatin capsules with "CellCept 250" printed in black ink on the blue cap and "ROCHE" on the brown body. Each capsule contains 250 mg of mycophenolate mofetil.

It is important to leave the capsules in the blister pack until you need a dose. When you are ready to take a dose, remove the number of capsules you need to make up the dose. Mycophenolate should be taken on an empty stomach. Swallow the capsules whole.

Like other anti-rejection medication, try to take your dose at the same time every day. Make sure your doctor, dentist, and pharmacist are aware of all medications you are taking, including anything you buy off the shelf, such as over-the-counter drugs and herbal or home remedies. Taking antacids at the same time as mycophenolate, for example, may affect the way mycophenolate works for you, so these drugs should not be taken together.

Like other medications, mycophenolate may cause side effects in some people. If you think you are experiencing side effects, talk to your doctor right away. Do not stop taking mycophenolate on your own.

Possible side effects of mycophenolate:

• nausea and vomiting
• diarrhea
• loss of appetite
• weakness
• swelling of legs and hands
• infection
• headaches

Some patients may experience side effects not listed above. If any side effect becomes bothersome or won't go away, contact your doctor, transplant clinic, or pharmacist.

Prednisone

Prednisone is a steroid, similar to one that your body produces normally. It decreases tissue swelling and suppresses rejection. The initial high dose of prednisone is gradually reduced until a low maintenance dose is established. Higher doses of steroids, called "pulse therapy", are used to treat acute rejection.

The most common side effects of prednisone are listed below. Again, remember that everyone responds differently to medications, so you may experience only some of these side effects or none at all.

Possible side effects of Prednisone:

• stomach upset (should always be taken with food)
• weight gain and fluid retention
• bone thinning
• fullness of the face
• acne/rash
• easy bruising
• joint pain
• mood swings
• medication induced diabetes (high blood sugars)
• infection

If you notice any of these side effects, tell a member of the transplant team. The team will make sure the problem is a side effect of the drug, and not a sign of rejection or another medical problem.

Taking Anti-rejection Drugs

It is important to take your medications at the same time each day so that you maintain adequate levels of medication in your blood. To ensure that the drugs work properly, you must take them exactly as prescribed.

If you miss your dose and it is less than half the time before your next dose is due, then take the missed dose. If it is more than half the time to your next dose, then skip the missed dose and wait for your next dose. Do not double your dose.

For example, if you were scheduled to take your medication every 12-hours and you remember to take your medication within 6-hours of the time it was due, then you can take the missed dose. If you have any questions regarding the schedule of your medications or taking missed doses, then make a note of the time and date of the missed dose and inform the transplant team as soon as possible. If you vomit within one hour of taking your medication, repeat the dose.

*Never change the dose of your drugs or stop taking them unless directed by the transplant team.

*Remember to always inform your doctor and dentist of the medications you are taking.

Rejection Episodes

It is likely that at some time you will experience an episode of rejection. It is referred to as an episode of rejection because it is usually a temporary, reversible event. It is most likely to occur in the first six months of having your new organ, but it can happen at any time as long as you have the organ.

Rejection may occur even if you have been taking your medications faithfully. While you may find this thought unsettling, it is a common occurrence. In most cases, with early detection and treatment, the transplant team should have no problem reversing the rejection completely.

The best way to fight rejection is to stop it before it starts, and to recognize it and treat it early. You can work at preventing rejection by taking your medications faithfully. For early detection learn to identify the signs and symptoms of rejection and report them immediately to the transplant clinic nurse.

Signs of Rejection

Early identification and reporting of symptoms are important in successfully treating and reversing rejection. Most rejection episodes are mild. It is common in fact to have no symptoms with rejection. Your doctor in the transplant clinic may suspect a rejection episode only because the creatinine has risen slightly above the previous level.

Rejection is diagnosed by a kidney biopsy. The results are usually available the next day.

On the other hand, some individuals may feel symptoms of the rejection episode. To ensure that the rejection is treated quickly, watch for any of the following warning symptoms:

• decreased urine output
• weight gain of one kilogram (2.2 pounds) per day, or more, sometimes with swelling of the ankles
• increased temperature/fever
• tenderness over transplant site
• shortness of breath while doing normal activities
• a general feeling of unwellness

If you experience any of these symptoms, report it to your transplant team immediately.

Treatment of Rejection

Rejection is usually determined by a renal biopsy done under guided ultrasound. This will confirm rejection or indicate the status of the transplanted kidney. Under local anesthetic a small piece of kidney tissue is removed with a biopsy needle and examined.

When rejection is detected, it must be treated immediately. Treatment usually involves high doses of a steroid, Solu-Medrol, which can be given intravenously (through an IV, called "pulse therapy") or by an increase in prednisone tablets taken orally. In most cases, this will reverse the rejection. The intravenous medication may be given in hospital or in the transplant clinic.

Blood work, especially the serum creatinine, is the best indicator of kidney function. You will have regular blood work done to monitor your creatinine levels to assess the effectiveness of the "pulse therapy".

If high doses of steroids are not effective, there are other treatment options that are very effective. However, these drugs are more potent, and therefore may carry more risk of infection or long-term malignancy with their use. Thus this treatment regime would only be used if other options weren't successful.

Chronic Rejection

Some transplant recipients may experience chronic rejection, a condition that most often occurs over a long period of time. Ongoing chronic rejection slowly damages the transplanted organ. Most often, chronic rejection has no symptoms. Your doctor may suspect this condition after noting a slow but steady rise in creatinine over the years. Chronic rejection is diagnosed by kidney biopsy. We don't fully understand the causes of chronic rejection, but possible explanations include very low and undetectable levels of acute rejection (so-called sub-clinical rejection), and some of the medications used to prevent acute rejection in the first place (such as cyclosporine). Unfortunately, unlike acute rejection, it is not possible to reverse the damage, and there is no proven therapy.

There is intense interest in transplantation now in understanding factors that are important in the development of chronic rejection, and clinical trials are underway to determine whether effective treatment strategies exist. As with acute rejection, chronic rejection can occur despite taking your medication regularly. You may need to change to a different anti-rejection drug.

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Infection

A possible side effect of anti-rejection drugs is an increase in infections. While suppression of the immune system is necessary to prevent organ rejection, it weakens the body's ability to fight off infections. Fortunately, there are ways of reducing the risk of infection while still maintaining adequate defenses against rejection.

The risk of contracting an infection is higher during the first few months following a transplant when your doses of anti-rejection drugs are high. As the doses fall, the risk of infection falls. As with rejection, the key to fighting an infection is to prevent it, identify it early, and treat it quickly.

Preventing Infection

The best way to prevent an infection is by avoiding close contact with people who may be ill. Most viruses, bacteria, and fungi are passed from person to person in tiny water droplets and may be transferred simply by shaking hands. Someone sneezing or coughing is sending out droplets, which you might breathe in, or transfer to your mouth or other mucous membrane (such as your eyes) with your hands.

During the first few months following your transplant, you must be diligent in avoiding infections. This may mean having to avoid normal close contact with family members or your spouse if they are sick.

You may not be able to prevent all infections, but you can certainly reduce the risk by washing your hands regularly and avoid putting your fingers in your mouth or touching your eyes. Family and friends with infections should also wash their hands before touching you.

Also avoid:

• people with colds or infections
• crowded, poorly ventilated, smoke-filled rooms
• public transportation, especially at rush hours
• public whirlpools
• activities that may cause breaks in the skin (when gardening, for example, wear gloves)
• changing cat and bird litter

It also helps to alert your co-workers to the fact that you are on immunosuppressants. You will find that people are remarkably considerate when they know the situation. After the transplant, you may be taking medications as a preventative measure against commonly occurring infections.

Medication and other costs

The three anti-rejection drugs you will be prescribed are available free of charge from the Transplant Outpatient Pharmacy located in the Transplant Clinic. Other non-immunosuppressive drugs must be purchased by you at your local pharmacy. Keep your receipts so you can apply for reimbursement of a portion of these costs through BC's Pharmacare Plan. Application forms are available from your pharmacy. For more information, talk to your pharmacist.

During the first three to six months, you may also be taking drugs to prevent infections, treat high blood pressure, or help with acid reflux, so the total cost of your medications will be quite high. Once you stop taking some of these drugs, the cost will come down significantly. Talk to your transplant team and other recipients about the best and cheapest places to buy your drugs.

Besides medications, there are other expenses that you may incur after your transplant, including:

• Accommodation in Vancouver before you can return to your community
• travel to and from the Transplant Clinic
• health monitoring equipment and supplies, such as blood pressure device, weight scale, and thermometer
• medic alert bracelet or necklace
• other supplies if required (gauze, tape, cleaning solutions)