Kidney Transplant: End-Stage Renal Disease

Various conditions can damage the kidneys, including both primary kidney diseases and other conditions that affect the kidneys.

• If kidney damage becomes too severe, the kidneys lose their ability to function normally. This is called kidney failure.
• Kidney failure can happen rapidly (acute kidney failure), usually in response to a severe acute (sudden, short-term) illness in another body system or in the kidneys. It is a very common complication in patients hospitalized for other reasons. It is often completely reversible with a resolution of the underlying condition.
• Kidney failure can also happen very slowly and gradually (chronic kidney failure), usually in response to a chronic (ongoing, long-term) disease such as diabetes or high blood pressure.
• Both types of kidney failure can occur in response to primary kidney disease as well. In some cases, this kidney disease is hereditary.
• Infections and substances such as drugs and toxins can permanently scar the kidneys and lead to their failure.

People with the following conditions are at greater-than-normal risk of developing kidney failure and end-stage renal disease:

• Diabetes (type 1 or type 2)
• High blood pressure, especially if severe or uncontrolled
• Glomerular diseases (These are conditions that damage the glomeruli, such as glomerulonephritis.)
• Hemolytic uremic syndrome
• Systemic lupus erythematosus
• Sickle cell anemia
• Severe injury or burns
• Major surgery
• Heart disease or heart attack
• Liver disease or liver failure
• Vascular diseases (These conditions, including progressive systemic sclerosis, renal artery thrombosis [blood clot], and scleroderma, block blood flow to different parts of the body.)
• Inherited kidney diseases (polycystic kidney disease, congenital obstructive uropathy, cystinosis, prune belly syndrome)
• Diseases affecting the tubules and other structures in the kidneys (acquired obstructive nephropathy, acute tubular necrosis, acute interstitial nephritis)
• Amyloidosis
• Taking antibiotics, cyclosporin, heroin, and chemotherapy (These can cause inflammation of kidney structures.)
• Gout
• Certain cancers (incidental carcinoma, lymphoma, multiple myeloma, renal cell carcinoma, Wilms tumor)
• HIV infection
• Vesicoureteral reflux (This is a urinary tract problem.)
• Past kidney transplant (graft failure)
• Rheumatoid arthritis

• Anemia
• Fluid retention
• Pulmonary edema (This is fluid retention in the lungs that can cause breathing problems.)
• High blood pressure from chemical imbalances and fluid retention
• Renal osteodystrophy (This is a weakening of the bones from calcium depletion, which can cause bones to fracture easily.)
• Amyloidosis (This is the deposition of abnormal proteins in the joints, which causes arthritis-like symptoms.)
• Stomach ulcers
• Bleeding problems
• Neurological damage
• Sleeping problems related to dialysis

The symptoms of kidney failure vary widely by the cause of the kidney failure, the severity of the condition, and the other body systems that are affected.

• Most people have no symptoms at all in the early stages of the disease, because the kidneys are able to compensate so well for the early impairments in their function. Others have symptoms that are mild, subtle, or vague.
• Generally, obvious symptoms appear only when the condition has become severe or even critical.
• Kidney failure is not painful, even when severe, although there may be pain from damage to other systems.
• Some types of kidney failure cause fluid retention. However, severe dehydration (fluid deficiency) can also cause kidney failure.
• Fluid retention (This causes puffiness, swelling of arms and legs, and shortness of breath [due to fluid collection in the lungs, called pulmonary edema].)
• Dehydration (This results in thirst, rapid heart rate [tachycardia], dry mucous membranes [such as inside the mouth and nose], and feeling weak or lethargic.)

Other common symptoms of kidney failure and end-stage renal disease include:

• Urinary problems (frequency, urgency)
• Bleeding due to impaired clotting, from any site
• Easy bruising
• Fatigue
• Confusion
• Nausea, vomiting
• Loss of appetite
• Pain in the muscles, joints, flanks, chest
• Bone pain or fractures
• Itching
• Pale skin (from anemia)

A person can prevent kidney failure, or slow the progression of the failure, by controlling underlying conditions. End-stage renal disease cannot be prevented in some cases.

• Kidney failure has usually progressed fairly significantly by the time symptoms appear. People at high risk of developing chronic kidney failure should see their doctor as recommended for screening tests.
• People with a chronic condition such as diabetes, high blood pressure, or high cholesterol should see their doctor regularly for monitoring and follow the treatment recommendations. Aggressive treatment of these diseases is essential to preserving kidney function and preventing complications.
• The person should avoid exposure to alcohol, drugs, chemicals, and other toxic substances as much as possible.

After Diagnosis of End-Stage Renal Disease

• When the doctor diagnoses an end-stage renal disease, he or she will discuss the treatment options with you. Whether kidney transplantation is an option for a patient depends on the specific situation. 
• If the doctor thinks the patient may be eligible for a transplant, he or she will learn about the pros and cons of this treatment. If a patient is a potential candidate, he or she will undergo a thorough medical evaluation. In the meantime, the patient will be treated with dialysis.
• Kidney transplantation is the replacement of nonworking kidneys with a healthy kidney from another person (the donor). 
• The healthy kidney (the "graft") takes over the functions of the nonworking kidneys. 
• A person can live normally with only one kidney as long as it functions properly.

Kidney transplantation surgical operation

• The surgeon places the new kidney in the lower abdomen and attaches it to an artery and vein in that area (usually the external iliac artery and vein).
• The kidney is also attached to the ureter, which carries urine from the kidney to the bladder.
• The patient's own kidneys are usually left in place unless they are causing problems, such as infection.
• Every operation has risks, but kidney transplantation is not a particularly difficult or complicated operation. It is the period after the surgery that is most critical. The medical team will watch very carefully to make sure that the new kidney is functioning properly and that the body is not rejecting the kidney.
• The patient must keep follow-up appointments with his or her transplant team to monitor for signs of rejection.
• The patient will have regular blood and urine tests to detect any signs of organ failure.
• One or more ultrasounds of the graft kidney may be done to see if there are structural abnormalities suggesting rejection.
• An arteriogram or nuclear medicine scan may be needed to confirm that blood is flowing to the transplanted kidney.

Is the patient eligible for a transplant?

Before a patient can receive a kidney transplant, he or she must undergo a very detailed medical evaluation.

• This evaluation may take weeks or months and require several visits to the transplant center for tests and examinations.
• The purpose of this thorough evaluation is to test whether the patient would benefit from a transplant and can withstand the rigors of the surgery, antirejection medications, and the adjustment to a new organ.

The medical team, which includes a nephrologist, a transplant surgeon, a transplant coordinator, a social worker, and others, will conduct a series of interviews with the patient and his or her family members.

• The patient will be asked many questions about his or her medical and surgical history, the medications he or she takes and has taken in the past, and habits and lifestyle.
• It will seem like they ask every imaginable question at least twice! It is important that they know every detail about the patient that could bear on a future transplant.
• They also want to make sure the patient is mentally prepared for following the necessary medication regimen.

The patient will also have a complete physical examination. Lab tests and imaging studies complete the evaluation.

• The patient's blood and tissue will be typed so that he or she can be matched to a donor's kidney. This significantly lessens the chance of rejection.
• The patient will have blood and urine tests to monitor his or her creatinine level, other organ functions, and electrolyte levels.
• The patient will have X-rays, ultrasounds, CT/MRI scans, and other imaging tests as needed to make sure the other organs are healthy and functioning.

Any of the following conditions significantly increase the patient's chance of rejecting the new kidney and may make him or her ineligible for transplant:

• Active cancer
• HIV infection
• Serious heart or lung disease
• Positive results for hepatitis C
• Severe infection
• Smoking
• Alcohol or drug abuse

Potential kidney donors also must be in good health and undergo a thorough medical evaluation.

If a patient is considered eligible for a transplant, every effort will be made to find a donor among his or her family members (who are most likely to match) and friends. If no suitable donor can be found, the patient's name will be added to the waiting list for a donor's kidney.

• This list is administered by the Organ Procurement and Transplantation Network, which maintains a centralized database of everyone waiting for a transplant and of living donors.
• OPTN is run by the United Network for Organ Sharing, a private nonprofit organization.
• Every new kidney that becomes available is tested and checked against this list to find the most perfect match.

One of the greatest concerns as a transplant recipient will be that the body's immune system will reject and attack the transplanted kidney. If not reversed, rejection will destroy the transplanted organ. For this reason, the patient and his or her family must keep aware of warning signs and symptoms of rejection. They must contact the transplant team immediately if any of these symptoms develop.

• Hypertension (high blood pressure): This is an ominous sign that the kidney is not functioning properly.
• Swelling or puffiness: This is a sign of fluid retention, usually in the arms, legs, or face.
• Decreased urine output

If the patient is a kidney transplant recipient, any of the following symptoms warrant immediate care at a hospital emergency department, preferably the hospital where the transplant was done.

• Fever: This is a sign of infection.
• Abdominal pain
• Tenderness, redness, or swelling at the surgical site
• Shortness of breath: This is a sign of fluid retention in the lungs.

The most critical part of kidney transplantation is preventing rejection of the graft kidney.

• Different transplant centers use different drug combinations to fight the rejection of a transplanted kidney.
• The drugs work by suppressing your immune system, which is programmed to reject anything "foreign," such as a new organ.
• Like any medication, these drugs can have unpleasant side effects.
• Immune-suppressing drugs. Some of the most common immune-suppressing drugs used in transplantation are described here.
  • Cyclosporine: This drug interferes with communication between the T cells of the immune system. It is started immediately after the transplant to suppress the immune system and continued indefinitely. Common side effects include
    • tremors,
    • high blood pressure, and
    • kidney damage.
  • These side effects are usually related to the dose and can often be reversed with proper dosing.
  • Corticosteroids: These drugs block T-cell communication as well. They are usually given at high doses for a short period immediately after the transplant and again if the rejection is suspected.
  • Corticosteroids side effects have many different side effects, including
    • easy bruising of the skin,
    • osteoporosis,
    • avascular necrosis (bone death),
    • high blood pressure,
    • high blood sugar,
    • stomach ulcers,
    • weight gain,
    • acne,
    • mood swings, and
    • a round face.

Because of these side effects, many transplant centers are trying to reduce the maintenance dose of the drug as much as possible or even to replace it with other drugs.

• Azathioprine: This drug slows the production of T cells in the immune system. Azathioprine is usually used for the long-term maintenance of immunosuppression. The most common side effects of this drug are suppression of the bone marrow, which produces blood cells, and liver damage. Many transplant centers are now using a newer drug called mycophenolate mofetil instead of azathioprine.
• Newer antirejection drugs include tacrolimus, sirolimus, and mizoribine, among others. These drugs are now being used to try to reduce side effects and to replace drugs after episodes of rejection.
• Other costly and experimental treatments include using antibodies to attack specific parts of the immune system to decrease its response.

These complications occur more frequently in people who have undergone kidney transplantation.

• Rejection
• Infection
• Certain cancers, such as
  • Basal cell carcinoma.
  • Kaposi sarcoma.
  • Carcinoma of the vulva and perineum.
  • Non-Hodgkin's lymphoma.
  • Squamous cell carcinoma.
  • Hepatobiliary carcinoma.
  • Carcinoma in situ of the uterine cervix.

Kidney Failure Relapse

• A small number of people who undergo transplantation for certain kidney diseases experience a return of the original disease after the transplant.
• High blood cholesterol level
• Liver disease
• Weakening of the bones

Women who wish to become pregnant are usually told to wait for 2 years after the operation. Many women have taken their pregnancies to term after transplantation, but there is an increased risk of kidney rejection and fetal complications.

• The patient, his or her family, and the transplant coordinators must keep in contact and close follow-up with the transplant team.
• Before leaving the hospital, the patient will be given instructions on proper doses and a schedule for antirejection medication. Keeping track of these medications is extremely important because they can actually harm the transplanted kidney if the doses are not appropriate.
• The patient will be taught how to measure his or her blood pressure, temperature, and urine output at home, and he or she should keep a log of these readings.
• The social worker and dietitian will counsel the patient before he or she leaves the hospital.

In the first few weeks after leaving the hospital, the patient will meet with members of the team frequently to monitor his or her recovery, review the logs, undergo blood tests, and adjust medication doses.

The outcome for kidney transplants continues to improve with advances in immune-suppressing medications.

• In the United States, the 3-year graft survival rate after transplantation varies between 83% to 94%.
• The earlier the patient can detect rejection, the better the chance it can be reversed and the new kidney's function preserved.