Nephrology nurses who primarily care for patients undergoing dialysis treatment have several roles involving transplantation. They educate and counsel patients regarding the option of transplantation, and they may assist patients undergoing the pretransplant evaluation. They also may need to provide dialysis treatments for transplant recipients who experience temporary loss of renal function from acute tubular necrosis (ATN) or a rejection episode and for patients with permanent loss of a transplanted kidney. Nephrology nurses and technicians also may provide dialysis for recipients of transplanted nonrenal organs, such as a liver or heart, who are experiencing acute kidney injury (AKI) or chronic kidney disease (CKD). Currently there are approximately 85,000 patients waiting for a renal transplant (United Network for Organ Sharing [UNOS], 2010) and the average waiting time for a kidney transplant is five to seven years according to the U.S. Renal Data System (USRDS, 2007). In 2008, 16,520 kidney transplants and 837 combined kidney-pancreas transplants were performed (NKF, 2010). The shortage of kidneys available for transplantation is quite severe. The average cost to Medicare for the first year post renal transplantation is $106,000. The average cost to Medicare for an individual with a functioning kidney transplant is $17,000 annually. Approximately 17,000 kidney transplants are performed annually and Medicare is the primary payer for more than half of these (NKF, 2009). The estimated cost of a kidney failure is $137,930 per patient for the first year after failure (Page & Woodard, 2008–2009).
What are the advantages of renal transplantation?
The most important advantage of renal transplantation is improved quality of life. Patients with a successful kidney transplant report a higher quality of life compared to patients receiving other forms of renal replacement therapy. With no need for dialysis treatment and more complete resolution of uremic symptoms, successful transplant recipients can experience a more “normal” lifestyle that includes family, social, and vocational activities. Another benefit is cost. Although the initial year post transplantation is more costly than one year of dialysis treatment, the subsequent years’ costs are significantly less. Finally, although the long-term survival rate for patients undergoing dialytic therapies has vastly improved, transplantation may offer patients the opportunity for longer survival. Since the introduction of cyclosporine, survival rates for transplant recipients are longer than for dialysis patients. This difference is most pronounced in individuals with diabetes mellitus.
What are the disadvantages of renal transplantation?
The disadvantages of transplantation stem from the need for lifelong immunosuppression to prevent the body from rejecting the transplanted organ. The necessity for daily medication compliance is a minor nuisance for some patients and an insurmountable hurdle for others. Especially in the initial postoperative period, family support can be crucial in ensuring adherence to what is often a daunting medication regimen.
Probably a more important disadvantage to transplantation is the vast potential complications of immunosuppression. Direct consequences of suppressing the immune system are increased risk of infection and some malignancies. The immunosuppressive medications also carry the potential for some nonimmunologic complications (such as bone disease, cataracts, diabetes mellitus, hyperlipidemia, and hypertension) and gastrointestinal complications (such as ulcers, hyperuricemia, and hyperkalemia). Obesity as well as more cosmetic side effects, such as hirsutism and gingival hyperplasia, may also occur.
Another major hurdle for many patients is the difficulty paying for the costly immunosuppressive medications. Although the Centers for Medicare & Medicaid Services (CMS) provides 80% coverage for the first 36 months after transplantation, many patients do not have other insurance coverage. Medicare did expand coverage of immunosuppressive medications from three years to a lifetime for transplant recipients who are over age 65 or disabled. Nondisabled transplant recipients under the age of 65 continue to receive only three years of coverage following transplantation. Nephrology nurses practicing in transplantation, along with social workers, assist transplant recipients in finding solutions to this problem.
The process of transplantation—from evaluation and waiting for a donor organ to the surgical hospitalization and threatened or actual rejection—places a great deal of stress on both the patient and family members. Again, strong social support is a crucial component of successfully coping with the stress of transplantation. Table 20-1 summarizes the risks and benefits of transplantation.
Table 20-1 The Transplantation Trade-off
|
Benefits |
Risk |
|
Improved quality of life |
Lifelong immunosuppression |
|
Freedom from dialysis |
Necessity for daily medication |
|
More normal lifestyle |
Increased risk of infection |
|
Longer survival rate |
Increased risk of malignancy |
|
Increased ability to pursue normal activities: work, home, school Normal calcium-phosphorus product Improved cardiac function Improved appetite Less restrictive diet Improved sexual function Increased feeling of wellness Increased mental acuity |
Loss of sick role Hypertension Ulcers, dyspepsia, other gastrointestinal effects Hyperkalemia, hyperlipidemia, obesity Body image changes; hirsutism, gingival hyperplasia Diabetes mellitus, gout, cataracts, tremor Psychologic stress |
|
Less costly than dialysis |
Difficulty paying for costly medications |
What are the risks and benefits of combined kidney-pancreas transplantation?
Dialysis patients who also suffer from diabetes mellitus may want to consider a combined kidney-pancreas transplant. For those individuals with hypoglycemic unawareness, the combined procedure is a lifesaver. The major benefits of this procedure are as follows:
• Euglycemia, which may halt or slow the progression of diabetic sequelae
• Freedom from frequent insulin injections and finger sticks for glucose measurement
The combined kidney-pancreas transplant procedure is more complicated and has more risks than kidney transplantation alone. These risks are associated with the following:
• Longer surgery.
• Exocrine drainage of the pancreas. Many transplant surgeons choose to drain amylase, a digestive enzyme made by the pancreas, to the urinary bladder using a piece of donor duodenum as a conduit. Although this procedure allows for monitoring of pancreatic function by measuring urinary amylase, the amylase may cause acute or chronic cystitis or urethritis. In addition, patients lose a great deal of bicarbonate and fluid and thus have a tendency to develop acidosis and dehydration.
• Increased immunosuppression-associated risks. The transplanted pancreas is much more prone to stimulate the body’s immune system than is a transplanted kidney, thus greater amounts of immunosuppression are required.
Who should be considered as a transplant candidate?
In general, all patients should be offered the option of consultation with a transplant team to determine their eligibility. Box 20-1 summarizes absolute and relative contraindications to transplantation.
Box 20-1 Absolute and Relative Contraindications to Transplantation
Absolute contraindications
Active infection
Active malignancy
Active substance abuse
Inability to comply with medication regimen
Relative contraindications
Age: very young or older than 65 years
Severe comorbidities
Lack of family support
Mental/psychologic problems
Can patients who are positive for human immunodeficiency virus receive a kidney transplant?
The USRDS (2008) reports that approximately 800 new CKD patients initiated dialysis treatment between 2002 and 2008 with a diagnosis of human immunodeficiency virus–associated nephropathy (HIVAN). HIVAN is the most common cause of renal failure in those with human immunodeficiency virus (HIV) (Carlson, 2008). In the past HIV was an absolute contraindication to transplantation because of concerns that the immunosuppressant therapy used in transplants might exacerbate the patient’s HIV infection. Other reasons were the shortage of organs available for transplantation and the shortened life expectancy rates of those infected with HIV. Today, most transplant centers do not perform transplants on HIV-positive patients; however, new findings suggest that it may be safe to perform transplants on some HIV-positive patients. Several transplant centers across the U.S. now perform renal transplants on carefully selected HIV-positive patients.
What screening is required pretransplantation for an hiv-positive patient?
The HIV-positive patient must meet all of the standard criteria for renal transplantation and undergo some additional screening. The goals of screening are to pick those individuals who will have the greatest transplant success while minimizing the progression of HIV. The candidate should have well-controlled HIV disease and an intact immune system. The immune system is assessed by HIV viral loads and CD4 counts. The patient’s history of opportunistic infections will also be assessed by the pretransplant workup team. A medication history review with special attention paid to any history of medication resistance will be evaluated. Screenings for tuberculosis and the human papillomavirus (HPV) are also reviewed. Each transplant center sets its own criteria for inclusion and evaluation.
What is the immunological basis of transplantation?
The immune system protects the body from foreign invasion by identifying the invaders and then destroying them. Anything that produces this response is called an antigen. The basis of immunology in transplantation is to identify how the body recognizes foreign antigens. Transplant immunologists have identified two main antigen systems that affect the acceptance or rejection of a transplanted organ or tissue. These two systems are blood groups and the human leukocyte antigen (HLA). Blood groups are the first determinant of compatibility for solid organ transplantation. In general, an organ must be ABO compatible with the recipient to be transplanted. For this reason, transplant recipient waiting lists are arranged by ABO group. The rhesus (Rh) factor is not applicable to solid organ transplantation. The four blood groups are O, A, B, and AB. Blood group O is the universal donor and blood group AB is the universal recipient. Blood group O can receive organs only from blood group O donors; recipients from blood group A can receive a kidney from blood groups A and O; recipients from blood group B can receive a kidney from blood groups B and O; and recipients from blood group AB can receive a kidney from blood groups A, B, AB, and O.
The HLA system is composed of a group of genes found on the sixth chromosome. Three main sites or loci on this chromosome—A, B, and DR—have been identified as influencing the recognition of foreign tissue. Because each individual has two of each chromosome, one donated by each parent, six loci are identified for each person. When tissue is introduced to the body with different HLA genes, the immune system is triggered and the rejection process begins.
The components of the immune system that are most important in transplantation are the T lymphocytes and B lymphocytes. T lymphocytes recognize the foreign tissue and initiate the rejection process. B lymphocytes recognize the foreign antigen and produce antibodies to destroy the invader. When presented, both T lymphocytes and B lymphocytes will remember a foreign antigen and attack it more quickly in subsequent presentations. Humans develop immunologic memory to HLA antigens through exposure via blood transfusions, pregnancy, and transplantation.
What is tissue typing?
Tissue typing refers to blood tests designed to identify the HLA genetic markers. Although HLA matching is used to distribute organs objectively, modern immunosuppressive medications have made HLA matching increasingly less important to successful outcomes. Many centers transplant organs with no HLA similarities (zero matched organs), as long as the crossmatch is negative, with excellent results. When the body recognizes and forms immunity to one HLA antigen, it often forms immunity to other related antigens, even though these antigens were not presented to the body. This crossover immunity has been recognized by the development of cross-reactive antigen groups (CREG) tests. CREG matching may improve outcomes in minority groups. UNOS began pilot studies with CREG matching in 1997.
What is crossmatching?
Monthly serum samples from potential recipients are used to perform crossmatching tests. Crossmatching tests are blood tests that determine whether a recipient has acquired immunity to a given donor organ tissue. The tests are performed when a donor organ becomes available. Serum from all eligible recipients is tested with donor lymph cells. A positive crossmatch means that the recipient has memory or acquired immunity to the donor and therefore cannot receive the organ. The routine test is the Amos antiglobulin test, which takes about six hours to complete, although more sophisticated and time-consuming tests, such as flow cytometry crossmatches, may sometimes be performed. In living donor transplantation, an additional test called a mixed leukocyte reaction (MLR) may be ordered, although this test takes several days to complete and has not proven to be of great value.
What are percent reactive antibody levels?
Another important crossmatching test is called percent reactive antibody (PRA). Antibodies form when the immune system is exposed to foreign antigens. The potential recipient’s serum is tested against a panel of random donors. The number of positive reactions to the donor panel is expressed as a percentage. This percentage represents the risk of a positive crossmatch and thus incompatibility with any random donor, along with an increased risk for acute or hyperacute rejection. Therefore, the higher a potential recipient’s PRA level, the less likely it is that any given organ will be compatible and the more difficult it is to find a compatible kidney. For this reason, patients with high PRAs are given preference in the distribution of organs from deceased donors. A patient with a PRA level greater than 80% is considered to be highly sensitized. Patients may be exposed to foreign HLAs through blood transfusions, viruses, pregnancy, or transplanted organs.
What is the purpose of the monthly serum samples?
The numbers of sensitized lymphocytes that constitute preformed immunity to any particular antigen may wax and wane over time. Sometimes the number may be so low that the patient’s PRA level may fall. Because of this phenomenon, sometimes a specific crossmatch using current serum will be negative even though the crossmatch using older or historic serum is positive. Because immunosuppression will be applied to block the memory response, a current negative crossmatch may indicate a window of opportunity for a potential recipient. On the other hand, immunity provoked by a blood transfusion after the most current serum sample was obtained could give a falsely negative crossmatch. The variability of immune status necessitates monthly serum samples for potential recipients.
What does the recipient workup entail?
The evaluation process for a kidney or other organ transplant begins with referral to the transplant center. The potential recipient and family members meet members of the transplant team. This team usually consists of transplant nurse coordinators, transplant surgeons, transplant nephrologists, and social workers. After the team has determined the initial eligibility of a candidate, the transplant nurse coordinator works with the patient, dialysis healthcare team, and primary healthcare provider to facilitate the evaluation. Although the evaluation may find that transplantation is not a viable option for some potential recipients, the ultimate goal of the pretransplant workup is to find out as much about the patient as possible to perform a successful transplant.
The evaluation generally consists of blood, urine, and other diagnostic tests (such as chest x-ray and electrocardiogram), as well as careful review of the patient’s records. Special attention is given to the following areas:
• Cardiovascular assessment, which may include cardiac arteriogram, echocardiogram, and stress testing
• Infection surveillance, which usually includes a dental examination
• Malignancy detection
• Genitourinary tract assessment
• Psychosocial evaluation, which may include screening for illicit drugs
What are the possible sources for organs?
Two main sources of kidneys for transplantation are living donors and deceased donors. Living donors can be related to the recipient by blood (parent, sibling) or otherwise emotionally connected (spouse, close friend, adopted child). The key requirements for living donation are voluntary informed consent and a completely healthy donor. Laboratory blood testing, immunologic testing, electrocardiogram studies, medical history and review, psychological evaluation, kidney function testing, and financial consultation are all tests investigated to determine whether someone can be a suitable donor.
Deceased donors are individuals who have died from irreversible brain death. Their bodies are kept functioning by artificial ventilation and medications. With the consent of next of kin, the organs and tissues are procured by the organ recovery team and distributed by the regional organ and tissue bank in accordance with national guidelines. There is no expense to the donor family and usual funeral arrangements are not affected by organ and tissue donation. There is currently a shortage in the U.S. of organs from deceased donors.
What is kidney paired donation?
Kidney paired donation is a procedure that occurs when an individual who wishes to donate a kidney to a significant other or family member is unable to do so because of incompatibilities. In paired donation, the incompatible donor and recipient are matched with another incompatible donor-recipient pair and the kidneys are exchanged between the pairs. This procedure allows both donors to donate and both recipients to receive compatible kidneys (Fig. 20-1).
Figure 20-1 Kidney paired donation.
What happens after a patient is placed on the deceased donor waiting list?
After a candidate is considered eligible for transplantation and no living donors are available, the transplant center places the candidate’s name on the deceased donor waiting list. Kidneys are distributed according to a point system. Points are given for length of time on the waiting list and degree of HLA match. Because of the difficulty in finding suitable kidneys for these patients, additional points are given to patients with high PRAs. In general, kidneys from deceased donors in one blood group are offered only to recipients in that same blood group; therefore, the waiting list is divided by blood group. When deceased donor kidneys are procured, the organ bank offers them to transplant centers in the following order:
1. Any potential recipient anywhere in the country who matches the donor at all six HLA loci
2. Locally, according to the point system
3. Regionally, and then nationally, according to the point system
Most kidneys are used locally. Other organs are also distributed in an equitable, objective manner, locally first, with medical need as the main determinant.
What is the responsibility of the dialysis team while the patient waits for a kidney?
Many patients wait one to two years before receiving their organ. It is important for the dialysis healthcare team to keep the transplant center informed regarding the health status of potential recipients and to make certain that no recipient misses his or her chance at an organ because of missing serum samples. Factors that affect waiting times are patient medical status, the availability of donors in the local area, and the level of match between the donor and the recipient.
Where are transplanted kidneys placed, and how long is the transplantation surgery?
The transplanted kidney and ureter are usually placed extraperitoneally in the right or left iliac fossa of the recipient. The incision extends from above the iliac crest to just above the symphysis pubis. Although the right iliac fossa is generally preferred for primary transplantation, either side may be used. If the recipient has had a previous transplant, the transplant surgeon generally will select the side not previously used. The donor renal artery is anastomosed end to end with the recipient internal iliac (hypogastric) artery or end to side with the external iliac artery. The venous anastomosis is generally end to side with the recipient’s external iliac vein. The donor ureter is attached to the recipient’s bladder or, rarely, the recipient’s ureter (Fig. 20-2). If a pancreas is also being transplanted, it will be placed in the opposite iliac fossa (Fig. 20-3). The kidney transplantation procedure generally lasts 2½ to 4 hours.
Figure 20-2 Transplanted kidney placement in the right iliac fossa.
(Modified from Black JM, Hawks JH, Keene AM: Medical-surgical nursing: clinical management for positive outcomes, ed 8, Philadelphia, 2009, Saunders.)
Figure 20-3 Technique of combined kidney-pancreas transplantation with the duodenal segment bladder drainage technique.
(From Sollinger HW et al: Experience with simultaneous pancreas-kidney transplantation, Ann Surg 208(4): 475–483, 1988.)
The iliac fossae are preferred placement sites even when the patient has had two or more transplantations. Occasionally, adhesions and scarring from multiple transplantations or other surgical procedures or severe atherosclerotic disease preclude the use of these sites. In these extremely rare cases, the surgeon may place the kidney intraperitoneally and use other vasculature, including the abdominal aorta.
How long do patients stay in the hospital after transplantation?
Transplant recipients are usually discharged three to five days after the transplantation procedure. Of course, surgical or medical complications may delay discharge, but the hospital stay may also be prolonged if the transplant team has concerns about the ability of the patient or the patient’s family to provide adequate postoperative care.
Why do some transplant recipients require dialysis?
Like other individuals, organ transplant recipients may require dialysis treatment for fluid removal, electrolyte imbalance, uremia, or a combination of these reasons. Renal—as well as extrarenal (such as liver and heart)—transplant recipients often need hemofiltration after surgery because of the vast amounts of fluids used to maintain cardiovascular stability during the procedure. The patient’s new kidney may be slow to respond to this fluid load. Kidney transplant recipients with ATN or an acute rejection attempt may require temporary dialysis. Recipients of extrarenal organs often have concomitant renal disease or acute renal failure. Uremia and/or electrolyte imbalances may occur in these patients as well. Fluid and solute removal via traditional hemodialysis, peritoneal dialysis, or methods such as slow continuous ultrafiltration or continuous venovenous hemofiltration may be employed.
What is acute tubular necrosis?
ATN occurs in up to 45% of all deceased donor kidney transplantations and rarely in living donor transplantations. ATN is characterized by oliguria (although high urine output ATN is occasionally seen) and failure of the serum creatinine to fall after a technically successful transplantation procedure. Its etiology is not well described, but it is probably due to a combination of factors, including preservation injury, prolonged cold storage time, vascular instability of the donor or recipient during the harvest or transplant procedure, and reperfusion injury. Cyclosporine may exacerbate or prolong ATN, and thus the initiation of cyclosporine therapy may be delayed in recipients with ATN. These individuals may require dialysis until the kidney begins to function, which generally occurs in several days to two weeks. ATN can last for several months with a good eventual outcome; however, oliguria and uremia that extend beyond two weeks may also be caused by rejection or drug-induced nephrotoxicity. A percutaneous biopsy of the kidney is usually performed to establish a diagnosis. Patients with ATN need reassurance and support from their caregivers. It is helpful to allow them to express their feelings about still requiring dialysis and to inform them that most transplanted kidneys with ATN eventually function well.
What special precautions should be taken when dialyzing a transplant recipient?
The following precautions are most notable when dialyzing a transplant recipient:
• During the initial 24 hours after surgery, internal bleeding is a concern, so hypotension should be carefully monitored and brought to the attention of the physician.
• Because of the susceptibility of the transplanted kidney to ischemia, avoid hypotension, even at the cost of decreased fluid removal.
• The integrity of the surgical incision must be maintained.
• Anticoagulation is also a concern in transplant recipients. Heparin-free or minimal anticoagulation is preferred, especially in the immediate postoperative period or if the recipient has undergone a diagnostic percutaneous renal biopsy.
• Electrolyte imbalances are common after transplantation. The most common is hyperkalemia. Hyperkalemia is common in patients with impaired graft function but is also caused by medications, such as cyclosporine and tacrolimus. Other electrolyte abnormalities are outlined in Table 20-2.
Table 20-2 Electrolyte Abnormalities after Transplantation
|
Abnormality |
Predisposing factors |
Treatment |
|
Hyperkalemia |
ATN |
Dialysis |
|
Hypokalemia |
Rapid posttreatment diuresis |
K+ supplements |
|
Hypocalcemia (often with hyperphosphatemia) |
Parathyroidectomy |
Calcium supplements |
|
Hypercalcemia (often with hypophosphatemia) |
Hyperparathyroidism + functioning kidney |
Diet |
|
Hypomagnesemia |
Diuresis |
Magnesium supplement |
|
Acidosis |
ATN |
Sodium bicarbonate |
ATN, Acute tubular necrosis; IV, intravenous; K+, potassium; PTH, parathyroid hormone.
Is there an increased risk of infection after transplantation?
Increased risk of infection is an inevitable consequence of immunosuppression. In the immediate postoperative period, bacterial infections in such sites as the wound, urinary tract, and lungs are more common, whereas such viral infections as cytomegalovirus (CMV), herpes simplex, and herpes zoster are more prevalent after the first several weeks following transplantation. CMV is a major cause of morbidity and mortality in transplant recipients. Many centers employ prophylactic medications, such as ganciclovir or hyperimmune gamma globulin, to prevent CMV infection or reactivation. Strict adherence to standard precautions should reduce the number of infectious complications in these patients. Isolation is rarely required, and transplant recipients pose no special risk to other patients or staff.
Does any one immunosuppressive medication place the transplant recipient at higher risk for malignancy?
Transplant recipients have demonstrated a higher risk than the general population for lymphoma, Kaposi sarcoma, cervical cancer, vulvar and perineal cancer, hepatobiliary cancers, sarcomas, and lip cancers. Not one immunosuppressant has been found to increase the risk; rather, the risk increases as the total amount of immunosuppression increases. When detected early, many of these cancers respond well to treatment.
What are the most commonly used immunosuppressive medications?
Immunosuppressive medications can be classified into five groups: steroids, calcineurin inhibitors, antimetabolites, antilymphocyte agents, and chimeric monoclonal antibodies. Table 20-3 outlines the major immunosuppressive medications used in organ transplantation. Most centers employ triple drug maintenance immunosuppressant therapy consisting of steroids, a calcineurin inhibitor, and an antimetabolite. Antilymphocyte preparations are used for a short time as rejection prophylaxis or treatment. All immunosuppressive medications carry the risk of infection and malignancy.
Table 20-3 Immunosuppressant Medications
Steroids.
Oral prednisone and intravenous methylprednisolone sodium (Solu-Medrol) are the most commonly used steroids. Steroids are used to both prevent and treat rejection. Steroids, although easy to use and inexpensive, have the potential for a vast number of side effects that can be minimized by using the lowest possible dose.
Calcineurin inhibitors.
Cyclosporine (Sandimmune, Neoral) and tacrolimus (FK 506, Prograf) are immunosuppressive drugs derived from fungi. These drugs block T-cell action by blocking the chemical signal calcineurin. Cyclosporine and tacrolimus have similar side effect profiles. Nephrotoxicity is a major problem with both medications, complicating the diagnosis of rejection. Tacrolimus offers the advantage of not sharing the cyclosporine effects of hirsutism, or gingival hyperplasia, and may not have as deleterious an effect on serum lipids as cyclosporine, but it is more likely than cyclosporine to cause diabetes and gastrointestinal symptoms. Tacrolimus is a more powerful immunosuppressant than cyclosporine, and thus the doses used are much smaller. The doses of both medications are based on blood levels obtained 12 hours after the last dose of medication. In most cases, these drugs are not used in combination but used interchangeably. A change of medication is usually precipitated by a severe rejection episode or intolerable side effects while receiving one of these medications. Cyclosporine—either as Sandimmune or Neoral, the more readily absorbed microemulsion form—is the primary drug used in kidney and heart transplantation. At many centers, tacrolimus is the primary agent employed in pancreas, liver, and small bowel transplantation.
Antimetabolites.
Azathioprine (Imuran) and mycophenolate mofetil (CellCept, Myfortic) are both antimetabolites. Mycophenolate mofetil is rapidly replacing azathioprine in transplantation because it appears to have an improved immunosuppressive effect, including action against beta cells. This beta cell–blocking action makes mycophenolate mofetil the only immunosuppressant that may treat chronic rejection.
Antilymphocyte preparations.
Atgam and OKT3 (Orthoclone) are the primary antilymphocyte agents used as prophylaxis against, or to treat, rejection. These powerful immunosuppressants are made by immunizing an animal with human lymphocytes and using the resultant antibodies. These antibodies block the function of T lymphocytes in the recipient. Atgam is a polyclonal preparation, which means it has antibodies against a host of human blood cells, including platelets and red blood cells. It is administered in a manner similar to that used for other serum products, using a central vein catheter. OKT3 is a product of genetic engineering; the only specific antibodies present are those that block the function of certain T lymphocytes known as CD3 cells. This monoclonal preparation is given as an intravenous push medication via a peripheral vein. The most serious side effects from OKT3 occur after the first or second dose and thus special precautions, including avoiding fluid overload, are observed.
Chimeric monoclonal antibodies.
Several new monoclonal antibodies have been developed for use in transplantation. Basiliximab (Simulect) and daclizumab (Zenapax) are similar drugs developed to prevent transplant rejection. They are both humanized or chimeric antibodies; that is, the majority of the antibody is partial human immunoglobulin with only a small portion being murine antibody. This humanization means that the body is less likely to recognize it as a foreign protein, and thus first-dose side effects are minimized, and the drug enjoys a prolonged half-life. Both drugs prevent rejection by interfering with interleukin-2 binding of lymphocytes. They are given intravenously in the first weeks after transplant. Basiliximab is given in two doses (two hours before transplantation and on postoperative day 4); the recommended course of daclizumab is five doses beginning immediately before surgery and then every other week. Both drugs appear to be similar in efficacy and safety.
Mammalian target of rapamycin.
Sirolimus (Rapamune) was approved for use by the U.S. Food and Drug Administration in 2000 for the prevention of organ rejection in patients receiving a kidney transplant. Sirolimus inhibits T lymphocyte activation and proliferation as well as antibody production, which makes it unique. This medication is initially taken in combination with cyclosporine and steroids. Cyclosporine can later be withdrawn from some patients with a low immunologic risk while the dose of sirolimus is increased. Side effects associated with this medication include increased serum cholesterol and triglycerides, hypertension, acne, fever, diarrhea, and rash. Increased creatinine levels may also be seen. This medication can be used for chronic rejection and is not nephrotoxic.
What is meant by rejection?
When the body’s immune system recognizes the transplanted organ as foreign, it will attempt to destroy it. This phenomenon is called rejection. Rejection is carried out in two ways: cellular or humoral. Cellular rejection is initiated by T lymphocytes, and humoral rejection refers to destruction of the transplanted organ by specific antibodies.
What are the different kinds of transplant rejections?
There are basically three types of rejection processes: hyperacute rejection, acute rejection, and chronic rejection. Rejection episodes represent a great amount of stress to the recipient and his or her family.
Hyperacute rejection.
Hyperacute rejection is a humoral rejection process primarily caused by preformed antibodies to the transplanted tissue HLA or to ABO antigens. This type of rejection occurs within minutes to hours of the transplantation procedure. The onslaught of specific antibodies causes massive intravascular coagulation and cell death. There is no treatment for hyperacute rejection. It is prevented by careful crossmatching.
Acute rejection.
When helper T lymphocytes recognize tissue cells as foreign, they initiate the cascade of events known as acute rejection. Acute rejection usually occurs weeks to months after transplantation. This form of cellular rejection generally occurs the first time the immune system is presented with a specific foreign tissue cell or antigen. The majority of immunosuppression is directed at preventing and treating acute rejection.
Chronic rejection.
In humoral rejection, beta cells, stimulated by nonself-antigens, produce antibodies to destroy the transplanted organ. Chronic rejection, also known as chronic allograft nephropathy, is a slow humoral rejection process that occurs months to years after transplantation. The hallmark of chronic rejection is gradual loss of function caused by fibrosis in the organ’s blood vessels. Chronic rejection of the kidney may be difficult to distinguish from chronic cyclosporine toxicity.
How is rejection diagnosed and treated?
Increased serum creatinine, in the absence of other causes, is most commonly used as the diagnostic indicator of rejection. A percutaneous biopsy may be used to confirm the diagnosis.
Hyperacute rejection.
Hyperacute rejection is often diagnosed as soon as the vascular anastomoses are completed and the clamps are released. The kidney will rapidly turn black and fail to produce urine, or the recipient may suffer severe symptoms of oliguria, fever, and pain soon after the transplantation procedure. There is no treatment; the organ must be surgically removed.
Acute rejection.
Oliguria, fever, edema, weight gain, and graft tenderness are the cardinal physical symptoms of acute renal transplant rejection. However, modern immunosuppression blocks these symptoms, causing transplant clinicians to rely on biochemical markers. A rapid rise in the serum creatinine over several days with or without physical symptoms may indicate acute rejection. Nephrotoxicity is also a possible diagnosis, especially if drug levels are high.
Many rejection attempts can be treated with increased steroids. The steroids are delivered by intravenous boluses or “pulses” of methylprednisolone and/or increased oral prednisone that is rapidly tapered back to baseline dose over several days. If the rejection is severe or does not respond to steroids, antilymphocyte preparations (Atgam, OKT3) are used. Most acute cellular rejections are treated successfully.
Chronic rejection.
Patients with chronic rejection often do not experience symptoms until the rejection has progressed to serious renal compromise. The serum creatinine slowly increases over months to years until the kidney ceases to function. Definitive diagnosis is made by biopsy. Traditionally there has been no treatment for chronic rejection; however, mycophenolate mofetil (CellCept), which has action against antibody-inducing beta cells, has demonstrated some success in treatment. Because it probably begins as very mild acute rejection, chronic rejection is best prevented by adequate immunosuppression and regular laboratory followup.
Who should provide long-term care and health maintenance after transplantation?
A variety of healthcare providers are qualified to provide long-term care to successful transplant recipients. These care providers include transplant physicians, nephrologists, internists, family practice physicians, and nurse practitioners. The goal of long-term care is to assist patients in achieving their maximum health potential. This goal is achieved by routine health maintenance, as well as a focus on the prevention, early detection, and treatment of the consequences of immunosuppression. As cardiovascular disease remains the number one cause of death in the first decade after successful renal transplantation, particular attention is paid to this area. Cancer and infection surveillance are also focus areas. The degree of rehabilitation to career, family, and social life is assessed and interventions are implemented if necessary.
What happens when the transplanted kidney irreversibly fails?
When the transplant team has determined that the transplanted kidney has irreversibly failed and that further treatment would be unsuccessful or detrimental, the patient returns to maintenance dialysis treatment. Except in cases of hyperacute rejection, early vascular catastrophe, or untreated acute rejection, the transplanted kidney usually slowly scars and shrinks as function ceases, so surgical removal is not necessary. Failed transplanted kidneys are removed in cases of severe hematuria, infection, or malignant hypertension. Immunosuppression is discontinued gradually to prevent superimposed acute rejection and to allow the adrenal glands to regain function.
These patients require special nursing care. In addition to the effects of immunosuppression, which may remain for several months, the failed transplant represents a crisis for the patient and family. The loss of the transplanted kidney may provoke depression, feelings of hopelessness, anger, and feelings of worthlessness. Individuals may experience a grieving process similar to the process described for those experiencing death and dying. Emotional support is essential for these patients. The dialysis staff should encourage the patient to seek another transplant, if appropriate.