Kidney Transplantation

One option for the person with ESRD is a new kidney. Transplants are most successful when the kidney comes from a living relative. Another option is a cadaver kidney (a kidney from an unrelated person who has just died).

One year after getting a kidney from a living relative, about 97% of people with diabetes are still alive. After 5 years, the number is approximately 83%. For people who get cadaver kidneys, about 93% are still alive after one year, and 75% are alive after 5 years.

These numbers may sound scary, but people who have kidney failure will die without treatment. For those who choose dialysis, only about one-third are still alive 5 years later. So although kidney transplantation is a serious operation, it offers people with ESRD their best chance for survival.

The body has a complex system for telling its own parts from foreign parts. To fool the body into accepting the donor organ, doctors try to match the donor and recipient for a blood protein called human leukocyte antigen (HLA) type. A good match is most important when using a kidney from a living donor. The evidence for the value of HLA matching with cadaver kidneys is less clear. Some doctors believe that, at least in African Americans, cadaver kidneys all "take" equally well.

Unfortunately, there are too few kidneys for all the people who need them. Not enough people sign up to be organ donors. The shortage persists even though each person gets only one kidney at a time. Although the body normally has two kidneys, it can get by with just one as long as that kidney is healthy and working well.

Federal law says that kidneys should be given out in a fair and efficient way. In the current system, a national list contains the names and HLA types of people who need cadaver kidneys. When a kidney donor's kidneys become available, doctors check the list to see whose HLA types best match that of the donor. If there are several people who match equally well, the two people waiting longest get the kidneys. Some people must wait years before a kidney becomes available. Those waiting use dialysis in the meantime.

Despite the best HLA matching, the body may still not recognize the new kidney as part of itself. For this reason, people with kidney transplants must take certain drugs the rest of their lives. These drugs are called immunosuppressants, because they suppress the immune system to keep it from fighting the new organ. These drugs include azathioprine and cyclosporine A. Despite these drugs, some kidney transplants fail. When the body attacks the new organ as foreign, it is called rejection.

Immunosuppressant drugs pose dangers. Although suppressing the immune system keeps it from noticing the foreign organ, it also keeps the immune system from noticing infections. As a result, the person can get sick more easily. These drugs also have many side effects.

A new kidney does not cure diabetes, and the disease may damage the new kidney just as it did the original ones. But it took many years for the person's own kidneys to fail. If the new kidney does develop diabetic nephropathy, it too will take many years to fail.

Benefits and Risks

Kidney transplants are safest in people who do not have heart or blood vessel disease. Before you get a transplant, your doctor will check your circulatory system to see if it is healthy enough to risk the operation.

As with any operation, the healthier you are, the better you can withstand the physical stress of surgery. Possible side effects of surgery include bleeding and infection.

Immunosuppressive drugs are hard on the body, but people who get transplants must take these drugs the rest of their lives. Azathioprine and cyclosporine, two commonly used drugs, make it easier for you to get infections and have other side effects. You will need to avoid people who have infections, such as a cold or the flu. Also, you should not be immunized without first checking with your doctor. These drugs can also damage the kidneys. For example, using either of these medicines for many years could increase your risk for some cancers.

Because of these risks, kidney transplants are done only in people whose kidneys are failing.

Pancreas Transplantation

In people with type 1 diabetes, the islet cells in the pancreas no longer produce insulin.  So it seems logical that giving a new pancreas to a person with type 1 diabetes would cure their disease.  Usually it does.

But the cure can be worse than the disease.  The body has a complex system for telling its own parts from foreign parts.  To fool the body into accepting the donor organ, doctors try to match the donor and recipient for a blood protein called human leukocyte antigen (HLA) type.  Patients with a transplanted organ must take immunosuppressive drugs in order to prevent the immune system from fighting the new organ.  The side effects of these drugs may be worse than the problems caused by diabetes, and the operation itself is serious.  One to two people in 10 die within a year of getting a pancreas transplant.  However, there are situations where a person has such severe complications from diabetes that having a pancreas transplant and taking these immunosuppressive drugs is no worse.  People with kidney transplants have to use these drugs anyway so, for these people, pancreas transplants can be worthwhile.

When the transplant takes, the patient no longer has diabetes and is unlikely to get it again.  Insulin shots and frequent blood glucose testing are no longer necessary.  Restoring normal blood glucose levels may stop complications from worsening, although many more studies are needed.

Pancreas transplants can be rejected, and roughly half of them are.  Pancreases attached so that they drain into the bladder are rejected less often than pancreases attached in other body sites.  When a transplant fails, the person gets diabetes again.

Remember that pancreas transplants work only for people with type 1 diabetes.  The major problem in people with type 2 diabetes isn't a failing pancreas, but the body's inability to respond to insulin in the right way.

Partial pancreas transplantation

Unfortunately, there are not enough cadaver pancreases to go around because not enough people sign up to be organ donors, and each pancreas must meet strict guidelines.  When a whole cadaver pancreas is not available, a person can receive a portion of a pancreas from a living relative.

When a patient with diabetes is receiving a kidney transplant from a living relative, it is usually beneficial to perform a partial pancreas transplant at the same time.  Since the transplanted kidney will become damaged by diabetes over time, transplanting a partial pancreas from the same donor will help control blood glucose levels and protect the new kidney from further damage. Transplant success seems higher when patients and donors are matched for HLA types, and a pancreas transplanted along with a kidney is less likely to fail than a pancreas transplanted alone.

Benefits and risks

Pancreas transplants are safest in people who do not have heart or blood vessel disease.  Before you get a transplant, your doctor will check your circulatory system to see if it is healthy enough to risk the operation.

As with any operation, the healthier you are, the better you can withstand the physical stress of surgery.  Possible side effects of surgery include bleeding and infection.

Immunosuppressive drugs are hard on the body, but people who get transplants must take these drugs the rest of their lives.  Azathioprine and cyclosporine, two commonly used drugs, make it more likely for you to get infections and have other side effects.  You will need to avoid people who have infections, such as a cold or the flu.  Also, you should not be immunized without first checking with your doctor.  These drugs can also damage the kidneys.  For example, using either of these medicines for many years could increase your risk for some cancers.

A recenty study (JAMA, 2003) has indicated that, for patients with functioning kidneys, survival rates of patients who receive pancreas-only transplants are worse than the survival rates of patients who manage their diabetes with conventional therapy (insulin, diet, etc.).  Therefore, the decision to have a pancreas-only transplant should be very carefully considered by both the patient and physician.  Because of the lower survival rates seen with pancreas-only transplants, and because a pancreas transplanted along with a kidney is less likely to fail than a pancreas transplanted alone, pancreas transplants are nearly always done only in people with type 1 diabetes who are getting or already have a transplanted kidney.

Islet Transplantation

If scientists can develop safe immunosuppressants that always work, then many people with type 1 diabetes may choose to have pancreas transplants. Until then, many doctors think islet transplants are a better option. Islets are clusters of cells in the pancreas that make insulin. In people with type 1 diabetes, islet cells are destroyed. Only 1-2% of the pancreas is made up of islet cells.

In pancreatic islet transplantation, cells are taken from a donor pancreas and transferred into another person. Once implanted, the new islets begin to make and release insulin. Researchers hope that islet transplantation will help people with type 1 diabetes live without daily injections of insulin.

The Edmonton Protocol

In the 1970s, islet transplant experiments were conducted with great success in laboratory mice. The excitement that those experiments generated soon turned to frustration, as initial attempts to reproduce that success in humans were largely disappointing. For many years progress was slow, and few transplant recipients were able to stay diabetes-free for more than a few months before the transplanted islet cells failed. But in recent years, scientists have begun to make rapid advances in transplant technology, and some of the most exciting new research comes to us from researchers at the University of Alberta in Edmonton, Canada. These scientists have used a new procedure called the Edmonton Protocol to treat patients with type 1 diabetes.

In this procedure, researchers use specialized enzymes to remove islets from the pancreas of a deceased donor. For an average-size person (70 kg), a typical transplant requires about 1 million islets, equal to two donor organs. Because the islets are extremely fragile, transplantation occurs immediately after they are removed.

The transplant itself is easy and takes less than an hour to complete. The surgeon uses ultrasound to guide placement of a small plastic tube (catheter) through the upper abdomen and into the liver. The islets are then injected through the catheter into the liver. The patient will receive a local anesthetic. If a patient cannot tolerate local anesthesia, the surgeon may use general anesthesia and do the transplant through a small incision.

It takes some time for the cells to attach to new blood vessels and begin releasing insulin. The doctor will order many tests to check blood glucose levels after the transplant, and insulin may be needed until control is achieved.

Benefits and Risks

Immunosuppressive or anti-rejection drugs are needed to keep the transplanted islets functioning. Researchers do not fully know what long-term effects these drugs may have. Also, although the early results of the Edmonton Protocol are very encouraging, more research is needed to answer questions about how long the islets will survive and how often the transplantation procedure will be successful.

However, transplanting islet cells has several advantages over transplanting a pancreas. First, unlike the pancreas transplant, an islet transplant is a minor surgical procedure, is less expensive, and is probably safer. Second, scientists may learn how to protect these cells from attack by the immune system. Several methods are already under study. If successful, the person with an islet transplant would not need to take immunosuppressants. Surgery would then be safer and more effective for many people with type 1 diabetes.

There is also continuing research on the transplantation of animal islets. Because the supply of human islets is severely limited, even the most successful method of human islet transplantation could only cure a small fraction of the people with diabetes through existing sources of human islets from donor pancreases. If islets from animal sources (for example, pigs) could be made to work successfully, a cure would be available for everyone. But transplants between species involve a whole new set of problems when it comes to regulating the body's immune response, so much work will still have to be done to make that a possibility.

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