week 14
mechanism of action calcineurin inhibitors
acts on t helper cells to prevent production and release of IL-2. Inhibits proliferation of T and B cells.
monoclonal antibodies
alemtuzumab (campath), basillximab (simulect), daclizumab (zenapax), muromonab-CD3 (orthoclone, OKT3)
considerations for organ transplant patient
rejection, infection, drug tox/side effects, malignancy, importance of adherence to regimen, renewed health and QOL
What accurately describes rejection after transplantation?
Hyperacute reaction can be avoided if crossmatching is done before transplantation.
The patient with an autoimmune disease will be treated with plasmapheresis. What should the nurse teach the patient about this treatment?
It will remove the IgG autoantibodies and antigen complexes from the plasma. Plasmapheresis removes plasma that contains autoantibodies (usually IgG class) and antigen-antibody complexes to remove the pathologic substances in the plasma without causing anemia.
The patient with an allergy to bee stings was just stung by a bee. After applying oxygen, removing the stinger, and administering epinephrine, the nurse notices the patient is hypotensive. What should be the nurse's first action?
Place patient recumbent and elevate the legs. In this emergency, the ABCs (airway, breathing, circulation) are being followed. For hypotension, the patient should be placed in a recumbent position with the legs elevated, epinephrine will continue to be administered every 2 to 5 minutes, and fluids will be administered with vasopressors.
Renal artery stenosis
Renal artery stenosis is due to scarring of surgical anastomosis
Mechanism of action of T cytotoxic lymphocyte activation and attack of transplanted tissue.
The transplanted organ is recognized as foreign and activates the immune system. T helper cells are activated to make interleukin -2 (IL-2) and T cytotoxic lymphocytes are sensitized. After the T cytotoxic cells proliferate, they attack the transplanted organ.
Sirolimus side effects
increased risk of infection, leukopenia, anemia, thrombocytopenia, hyperlipidemia, hypercholesterolemia, arthralgias, diarrhea, increased incidence of cancer
mycocephenolate mofetil
inhibits purine synthesis, suppresses proliferation of T and B cells
Azathioprine (Imuran) MOA
inhibits purine synthesis, suppresses proliferation of T/B cells
Muromonab-CD3 (Orthoclone OKT3) MOA
monoclonal antibody that binds to CD3 receptors on T cells, causing cell lysis. Inhibits function of T cells
most commonly transplanted solid organs
kidney, heart, liver
immunosuppression protocols
1. Induction therapies - intraoperative or postoperative for short period of time to induce tolerance to new transplanted graft 2. Maintenance therapies - taken for the life of the allograft - "Triple Drug Therapy" 3. Antirejection therapies (rescue therapies) - used during rejection episodes 1. Monoclonal antibodies (Example: Muromonab-CD3): interferes with T cell function and decreases # of circulating T cells. - **Flu-like syndrome likely to occur following treatment. - Pre-medicate with acetaminophen, diphenhydramine, and IV methylprednisolone before administration 2. Polyclonal antibodies (Examples: horse antithymocyte globulin and rabbit antithymocyte globulin): animals create antibodies to injected human lymphoid cells - **allergic reaction to foreign animal proteins may occur - Decrease side effects by administering slowly - Pre-medicate with acetaminophen, diphenhydramine, and IV methylprednisolone before administration
Increased risk factors for kidney transplantation surgery:
70+ (lifelong risk for increased complications, lifelong immunosuppression, and organ rejection), BMI 41 (morbidly obese), client who requires NPH insulin for type 1 diabetes mellitus, past history of lymphoma (history of cancer)
1 donor can save how many lives?
8
Which patient is at risk for developing graft-versus-host disease (GVHD)?
A 40-yr-old woman who received a bone marrow transplant from a close relative. GVHD occurs when an immunoincompetent patient is transfused or transplanted with immunocompetent cells. Examples include blood transfusions or the transplantation of bone marrow, fetal thymus, or fetal liver.
thrombosis
A blood clot can form in a major vessel of the transplanted kidney.
ischemia
A delay in transplanting the donor kidney after harvesting can result in hypoxic injury of the donor kidney.
4 components of compatibility testing
ABO blood typing, HLA typing, PRA, crossmatch
Postop care following a kidney transplant
Actions that the nurse should include obtain daily weights, assess dressings for bloody drainage, replace hourly urine output with IV fluids, monitor blood electrolytes
azathioprine (imuran) side effects
Bone marrow suppression (neutropenia, anemia, thrombocytopenia)
Ten days after receiving a bone marrow transplant, a patient develops a skin rash on the palms, soles of feet, jaundice, and diarrhea. What does the nurse determine these clinical manifestations are indicating?
Cells in the transplanted bone marrow are attacking the host tissue. The patient's symptoms are characteristic of graft-versus-host-disease (GVHD) in which transplanted cells mount an immune response to the host's tissue. The target organs for the GVHD phenomenon are the skin, liver, and GI tract.
treatment of chronic rejection
Conservative (monitor kidney status, continue immunosuppressive therapy) until dialysis is required
alemtuzamab route
IV
Acute rejection
Occurs 1 week to 2 years after surgery
daclizumab and basillximab side effects
acute hypersensitivity, anaphylaxis
daclizumab and basillximab MOA
monoclonal antibody that targets IL-2 receptor and inhibits T cell activation and proliferation
alemtuzamab MOA
monoclonal antibody that targets the CD52 antigen on T and B cells, monocytes, and macrophages. Causes prolonged T cell depletion.
Cyclophosphamide side effects
neutropenia, hemorrhagic cystitis
Side effects of corticosteroids
peptic ulcers, hypertension, osteoporosis, Na and H20 retention, muscle weakness, easy bruising, delayed healing, hyperglycemia, increased risk for infection
everolimus side effects
peripheral edema, constipation, hypertension, nausea, anemia, UTI, hyperlipidemia
treatment of a hyperactue rejection
◦ : Immediate removal of the donor kidney
organ rejection
NURSING ACTIONS: Monitor for and report manifestations of rejection immediately.
chronic rejection
Occurs gradually over months to years
Everolimus (Zortress) route
PO
sirolimus rapamune route
PO
Azathioprine (Imuran) route
PO, IV
cyclophosphamide route
PO, IV
mycocephenolate mofetil (cellcept, myfortic) route
PO, IV
HLA typing
Testing of important genetic protein marker antigens. 6 antigens are currently thought to be clinical significant for transplantation.
etiology of hyperacute reaction
An antibody-mediated response causing small blood clots to form in the transplanted kidney that occlude vessels and result in massive cellular destruction. The process is not reversible.
client education ischemia
Dialysis might be needed until the donor kidney heals.
immunosuppressive solution
Use a combination of medications with different mechanisms of action at relatively low doses
everolimus and Sirolimus MOA
binds to mechanistic target of rapamycin (mTOR), thereby suppressing T cell activation and proliferation
corticosteroids
prednisone, methlyprednisolone
cause of acute rejection
◦ An antibody-mediated response causing vasculitis in the donor kidney, and cellular destruction starts with inflammation that causes lysis of the donor kidney
daclizumab and basillximab route
IV
polyclonal antibodies route
IV
Muromonab-CD3 (Orthoclone OKT3) route
IV push
betlaclept (nulojix)
IV, prevents activation of T cells, anemia, diarrhea, constipation, UTI, peripheral edema
Association between HLA antigens and diseases is most commonly found in what disease conditions?
autoimmune disorders
cytotoxic antiproliferative drugs
azathioprine (imuran), cyclophosphamide, everolimus (zortress), mycophenolate mofetil (cellcept, myfortic), sirolimus (rapamune)
polyclonal antibodies
horse antithymocyte globulin (atagam), rabbit antithymocyte globulin (thymoglobulin, ATG)
cyclophosphamide mechanism of action
cross-links DNA, leading to cell injury/death, results in decrease in number and activity of T and B cells
side effects of mycophenolate mofetil
diarrhea, nausea/vomiting, neutropenia, thrombocytopenia, increased risk of infection, increased incidence of cancer
The majority of organ donations come from living donors
false
alemtuzmab side effects
fever, chills, dyspnea, chest pain, n/v, neutropenia, anemia, thrombocytopenia, increased risk for opportunistic infections
Muromonab-CD3
fever, chills, dyspnea, chest pain, nausea, vomiting. Anaphylactic reactions include pulmonary edema, cardiac, or respiratory arrest
polyclonal antibodies side effects
fever, chills, dyspnea, myalgia, chest pain, nausea, vomiting, anaphylaxis, leukopenia, thrombocytopenia, rash, increased risk for infection
mechanism of action polyclonal antibodies
prepared by immunizing horse or rabbit with human thrombocytes or T cells. Polyclonal antibodies directed against T cells, thus depleting them
goals of immunosuppressant therapy
prevent rejection of transplanted organ, minimize infection/cancer development
A patient waiting for a kidney transplant asks the nurse to explain the difference between a negative and positive crossmatch. Which statement by the nurse would be the most accurate response?
"A negative crossmatch means that no preformed antibodies are present, and the transplant would be safe." A crossmatch uses serum from the recipient mixed with donor lymphocytes to test for any preformed antibodies to the potential donor organ. A positive crossmatch indicates that the recipient has cytotoxic antibodies to the donor and is an absolute contraindication to transplantation. A negative crossmatch indicates that no preformed antibodies are present, and it is safe to proceed with transplantation.
Which statement by the patient who had an organ transplant would indicate that the patient understands teaching about immunosuppressive medications?
"The lower doses of my medications can prevent rejection and minimize the side effects." Because immunosuppressants work at different phases of the immune response, lower doses of each drug can be used to produce effective immunosuppression while minimizing side effects.
crossmatch
A crossmatch is done to determine the existence of antibodies against the potential donor. A crossmatch uses serum from the recipient mixed with donor lymphocytes to test for any preformed anti-HLA antibodies to the potential donor organ. The crossmatch can be used as a screening test when possible living donors are being considered or once a cadaver donor is chosen. A negative crossmatch means that no preformed antibodies are present, and it is safe to go ahead with transplantation. A positive crossmatch means that the recipient has cytotoxic antibodies to the donor, which is an absolute contraindication in living donor transplants. Live donor transplants may be done for patients with a positive crossmatch if no other live donors (with a negative crossmatch) exist. In this situation, plasmapheresis or IVIG can be done to remove antibodies. It is not always possible to complete a crossmatch prior to transplantation. If a retrospective crossmatch is done, the results will have implications for immunosuppression protocols after the transplant. A prospective crossmatch is especially important for kidney transplants. It may not be done for lung, liver, and heart transplants. People can indicate their wish to become a donor when they sign a donor card or driver's license or join a donor registry (depending on the state). However, on their death or imminent death, the person's legal next of kin may need to consent to the donation. Legal requirements and the facility's policy for a donor's legal next of kin to consent regardless of whether the donor's wishes varies from state to state and from facility to facility. Currently more than 116,000 people are on the organ procurement and transplantation network's national waiting list. This list is maintained by the United Network for Organ Sharing (UNOS). However, fewer than 35,000 people receive transplants annually. The organs in highest demand are kidneys, hearts, and livers. These are also the most often transplanted organs. The Uniform Anatomical Gift Act regulates organ and tissue donations to allow for fair and consistent transplantation laws among all states. Patients are matched to available donors based on a number of factors: ABO blood and HLA typing, medical urgency, time on the waiting list, and geographic location.
kidney transplant
A kidney transplant can greatly improve the quality of life for clients whose kidneys no longer function adequately to sustain life (related to end-stage kidney disease) and are otherwise dialysis-dependent. The recipient's tissue must be matched with a donor's. Donors for kidney transplantation can be living, non-heart-beating, or cadaver donors. In-depth tissue typing includes assessment of blood type (ABO) compatibility and histocompatibility, including human leukocytic antigen and other minor antigens. Clients receiving a donor kidney from a living, related donor with matching tissue type have the greatest chance of graft survival. Kidneys used from cadaver or non-heart-beating donors must be sufficiently perfused to maintain viability of the organ. The donated kidney is surgically implanted in the client.
Panel Reactive Antibody (PRA)
A panel of reactive antibodies (PRA) shows the recipient's sensitivity to various HLAs before receiving a transplant. To detect preformed antibodies to HLA, the recipient's serum is mixed with a randomly selected panel of donor lymphocytes to determine reactivity. The potential recipient may have been exposed to HLA antigens by previous blood transfusions, pregnancy, or a previous organ transplant. PRA allows for the determination of whether a recipient is of high or low reactivity to potential donors. The results for the PRA are calculated in percentages. A high PRA indicates that the person has a large number of cytotoxic antibodies and is highly sensitized, which means there is a poor chance of finding a crossmatch-negative donor. In patients awaiting transplantation, a PRA panel is usually done on a regular basis. In highly sensitized patients (high PRA), plasmapheresis and IV immunoglobulin (IVIG) can be used to lower the number of antibodies.
In a person having an acute rejection of a transplanted kidney, what would help the nurse understand the course of events?
Acute rejection can be treated with OKT3. Repeated episodes of acute rejection can lead to chronic rejection. Acute rejection is common after a transplant and can be treated with drug therapy.
acute rejection
Acute rejection most often occurs in the first 6 months after transplantation. This type of rejection is usually a cell-mediated immune response by the recipient's lymphocytes, which have been activated against the donated (foreign) tissue or organ. In addition to cell-mediated rejection, another type of acute rejection occurs when the recipient develops antibodies to the transplanted organ (humoral rejection). It is common to have at least 1 rejection episode, especially with organs from deceased donors. These episodes are usually reversible with additional immunosuppressive therapy. This may include increased corticosteroid doses or polyclonal or monoclonal antibodies. Unfortunately, immunosuppressants increase the risk for infection. To combat acute rejection, all patients with transplants need long-term use of immunosuppressants, putting them at a high risk for infection, especially in the first few months after transplant when the immunosuppressive doses are highest.
risk factors for end stage kidney disease
Conditions that increase the risks involved in kidney transplantation surgery, lifelong immunosuppression, and organ rejection ◦ Age younger than 2 years ◦ Age older than 70 years (Older adult clients are at risk for developing advanced heart disease and malignancies, which increases the risk for complications with kidney transplantation surgery.) ◦ Advanced, untreatable cardiac disease ◦ Active cancer ◦ Chronic infections or systemic diseases (HIV, hepatitis B or C) ◦ Coagulopathies and certain immune disorders ◦ Morbid obesity ◦ Diabetes mellitus ◦ Chronic pulmonary disease ◦ Untreated gastrointestinal diseases, such as peptic ulcer disease
PRA
Determines whether a potential recipient is of high or low reactivity to a potential donor. increased PRA = increased sensitivity = decreased chance of finding a crossmatch (-) donor
A nurse is teaching organ rejection after kidney transplant?
Expect an immediate removal of the donor kidney for a hyperacute rejection, a fever and fluid retention is a sign of acute rejection, immunosuppressants are increased to treat acute rejection, dialysis can be required as a conservative treatment to monitor the client's kidney function for the progression of chronic kidney failure following kidney transplant.
findings of chronic rejection
Gradual return of azotemia, fluid retention, electrolyte imbalance, and fatigue
GVHD
Graft-versus-host disease (GVHD) occurs when an immunodeficient patient receives immunocompetent cells. A GVHD response is most common in hematopoietic stem cell transplants. In most transplantation situations, the biggest concern is the patient's (host's) rejection of the organ or transplant. However, in GVHD disease, the graft (donated tissue) rejects the host (recipient) tissue. The GVHD response may begin 7 to 30 days after transplantation. Once the reaction is started, little can be done to change its course. The exact mechanism involved in this reaction is not completely understood. However, it involves donor T cells attacking and destroying vulnerable host (recipient) cells. The target organs for the GVHD phenomenon are the skin, liver, and GI tract. The skin disease may be a maculopapular rash, which may be pruritic or painful. It initially involves the palms and soles of the feet but can progress to a generalized erythema with bullous formation and desquamation (shedding of the outer layer of skin). The liver disease may range from mild jaundice with high liver enzymes to hepatic coma. GI manifestations may include mild to severe diarrhea, severe abdominal pain, GI bleeding, and malabsorption. The biggest problem with GVHD is infection, with different types of infections seen in different periods. Bacterial and fungal infections predominate right after transplantation when granulocytopenia exists. The development of interstitial pneumonitis is the primary concern later. There is no adequate treatment of GVHD once it is established. Although corticosteroids are often used, they enhance the susceptibility to infection. The use of immunosuppressive agents (e.g., methotrexate, cyclosporine) has been most effective as a preventive rather than a treatment measure. Radiating blood products before they are given is another way to prevent T-cell replication. Ibrutinib (Imbruvica), a kinase inhibitor that is used to treat several forms of leukemia and lymphoma, is an option for some patients with chronic GVHD.
hyperacute rejection
Hyperacute rejection occurs within 24 hours after transplantation because the blood vessels are rapidly destroyed. It occurs because the person had preexisting antibodies against the transplanted tissue or organ. There is no treatment for hyperacute rejection, and we must remove the transplanted organ. Fortunately, hyperacute rejection is a rare event because of improved immunosuppression medications and because the final testing prior to transplantation usually determines whether the recipient is sensitized to any of the donor HLAs.
A patient with systemic lupus erythematosus is receiving plasmapheresis to treat an acute attack. What symptoms will the nurse monitor to determine if the patient develops complications related to the procedure?
Hypotension, paresthesias, and dizziness. Common complications associated with plasmapheresis are hypotension and citrate toxicity. Citrate is used as an anticoagulant and may cause hypocalcemia, which may manifest as headache, paresthesias, and dizziness.
client education renal artery stenosis
Monitor for peripheral edema and have blood pressure checked often.
Hyperacute rejection
Occurs within 48 hr after surgery
Living donors can donate what organs?
One Kidney, Section of the liver, part of lung, pancreas, and intestine
calcineurin inhibitor route
PO, IV
corticosteroids route
PO, IV
sirolimus
Rapamune suppresses T-cell activation and proliferation. It is used in combination with corticosteroids, cyclosporine, and/or tacrolimus.
transplant rejection
Rejection is 1 of the major problems after organ transplantation. Organ rejection occurs as a normal immune response to foreign tissue. The risk for rejection is reduced by using immunosuppression therapy, performing ABO and HLA matching, and ensuring that the crossmatch is negative. Unfortunately, many different HLAs exist. A perfect match is nearly impossible unless the tissue is from one's self, an identical twin, or in some cases a sibling. Rejection can be hyperacute, acute, or chronic. Prevention, early diagnosis, and treatment of rejection are essential for long-term graft function.
polyclonal antibodies
T cells include horse antithymocyte globulin (Atgam) and rabbit antithymocyte globulin (thymoglobulin, ATG). These agents are derived by injecting animals (rabbit or horse) with human lymphoid cells, then procuring and purifying the resultant antibody. They are often used for induction immunosuppression and treatment of acute rejection. Allergic reactions to the foreign proteins from the host animal, manifested by fever, arthralgias, and tachycardia, are common but usually not severe enough to prevent use. These side effects can be decreased by giving the preparation slowly, over 4 to 6 hours, and premedicating patients with acetaminophen, diphenhydramine, and methylprednisolone. The main toxicities of polyclonal antibodies are leukopenia and thrombocytopenia. They are caused by antibody contaminants that are not completely removed during preparation of the antibodies.
HLA system
The antigens responsible for rejection of genetically unlike tissues are called the major histocompatibility antigens. These antigens are products of histocompatibility genes. In humans, they are called the human leukocyte antigen (HLA) system. The genes for the HLA antigens are linked and occur together on the sixth chromosome. HLAs are present on all nucleated cells and platelets. We primarily use the HLA system in matching organs and tissues for transplantation. An important characteristic of HLA genes is that they are highly polymorphic (variable). Each HLA locus can have many different possible alleles, and thus many combinations exist. Each person has 2 alleles for each locus, 1 inherited from each parent. Both alleles of a locus are expressed independently (i.e., they are codominant). The proteins encoded by certain genes are known as antigens. The entire set of A, B, C, D, and DR genes (the HLA genes) on 1 chromosome is termed a haplotype. A complete set is inherited as a unit (haplotype). One haplotype is inherited from each parent. This means that a person has HLA genes that are half identical to those of each parent. The HLA genes of 1 person have a 25% chance of being identical to the HLA genes of a sibling. In organ transplantation A, B, and DR are primarily used for compatibility matching. The specific allele at each locus is identified by a number. For example, a person could have an HLA of A2, A6, B7, B27, DR4, and DR7. Currently more than 8000 HLA alleles have been identified for the various HLA genes.
HLA and disease
The early interest in HLAs was stimulated by the role of HLAs in matching donors and recipients of organ transplants. Since that time, the interest in the association between HLAs and disease has grown. Several diseases show significant associations with specific HLA alleles. People who have these alleles are much more likely to develop the associated disease than those who do not have the alleles. However, having a particular HLA allele does not mean that the person will necessarily develop the associated disease—only that the relative risk is greater than in the general population. Most of the HLA-associated diseases are classified as autoimmune disorders. Examples of HLA types and disease associations include (1) HLA-B27 and ankylosing spondylitis; (2) HLA-DR2, HLA-DR3, and SLE; (3) HLA-DR3, HLA-DR4, and diabetes; and (4) HLA-DR2 and narcolepsy. The discovery of HLA associations with certain diseases was a major breakthrough in understanding the genetic bases of these diseases. It is now known that at least part of the genetic bases of HLA-associated diseases lies in the HLA region, but the actual mechanisms involved in these associations are still unknown. However, most people who inherit a specific HLA type (e.g., HLA-DR3) that is associated with a disease will never develop that disease. Currently the association between HLAs and certain diseases is of minimal practical clinical importance. Nevertheless, there is promise for the development of clinical applications in the future. For example, with certain autoimmune diseases, it may be possible to identify members of a family at greatest risk for developing the same or a related autoimmune disease. These people would need close medical supervision, implementation of preventive measures (if possible), and early diagnosis and treatment to prevent chronic complications.
tissue typing
The recipient usually receives a transplant from an ABO blood group-compatible donor. The donor and recipient do not need to share the same Rh factor.
calcineurin inhibitors
This group of drugs, including tacrolimus (Prograf) and cyclosporine (Sandimmune), is the foundation of most immunosuppression regimens. As the most effective immunosuppressants, these drugs prevent a cell-mediated attack against the transplanted organ. They are generally used in combination with corticosteroids, mycophenolate mofetil, and sirolimus. Tacrolimus is the most widely used calcineurin inhibitor. Cyclosporine is being used less often. They do not cause bone marrow suppression or change the normal inflammatory response. Many of the side effects are dose related. These drugs are potentially nephrotoxic. We monitor drug levels closely to prevent toxicity -drug alert for tacrolimus and cyclosporine: a substance in grapefruit (juice) prevents metabolism of these drugs, consuming while using increases toxicity
chronic rejection
a process that occurs over months or years and is irreversible. Chronic rejection can occur for unknown reasons or from repeated episodes of acute rejection. Large numbers of T and B cells infiltrate the transplanted organ, indicating ongoing, low-grade, immune-mediated injury. Chronic rejection results in fibrosis and scarring. In heart transplants it manifests as accelerated coronary artery disease. In lung transplants it manifests as bronchiolitis obliterans. In liver transplants, we see a loss of bile ducts. In kidney transplants it manifests as fibrosis and glomerulopathy. There is no definitive therapy for this type of rejection. Treatment is primarily supportive. This type of rejection is hard to manage and is not associated with the optimistic prognosis of acute rejection.
End stage Kidney disease expected findings:
anuria, marked azotemia (elevated BUN and blood creatinine), crackles in lungs (pulmonary edema, hypervolemia), decreased calcium level, proteinuria
Age related disorder nurses should assess for related to the increased immunologic response
autoimmune response. With aging, autoantibodies increase, which lead to autoimmune diseases (e.g., systemic lupus erythematosus, acute glomerulonephritis, rheumatoid arthritis, hypothyroidism). Cell-mediated immunity decreases with decreased thymic output of T cells and decreased activation of both T and B cells. There is a decreased or absent delayed hypersensitivity reaction. Immunoglobulin levels decrease and lead to a suppressed humoral immune response in older adults.
The function of monocytes in immunity is related to their ability to
capture antigens by phagocytosis and present them to lymphocytes.
Cyclosporine instructions after a kidney transplant: monitor for and report a sore throat to your provider
client should report any manifestations of an infection because this medication causes immunosuppression (sore throat). Client should report manifestations of hepatoxicity, such as jaundice and abdominal pain. Shouldn't drink grapefruit juice which can reduce cyclosporine metabolism and cause increased cyclosporine levels. Protein rich food promotes healing and rebuilds muscle-no restrictions.
standard triple therapy for maintenance
corticosteroids (prednisone), calcineurin inhibitor (tacrolimus), cytotoxic (antiproliferative drugs)- mycophenolate mofetil
Calcineurin inhibitors
cylosporine (sandimmune, neoral, gengraf), tacrlimus (prograf)
HLA typing
done on potential donors and recipients. Currently we think only the A, B, and DR antigens are clinically significant for transplantation. Because each locus has 2 alleles that encode for antigens, a total of 6 antigens is identified. In transplantation we try to match as many antigens as possible between the HLA-A, HLA-B, and HLA-DR loci. Antigen matches of 5 and 6 antigens and some 4-antigen matches have better clinical outcomes (i.e., the patient is less likely to reject the transplanted organ), especially in kidney and bone marrow transplants. The degree of HLA matching needed or suitable for successful solid organ transplantation depends on the type of organ and degree of acceptable risk. Certain organ and tissue transplants need a closer histocompatibility match than other organs. For example, a cornea transplant can be accepted by nearly anyone because corneas are avascular and therefore no antibodies reach the cornea to cause rejection. In kidney and bone marrow transplantation, HLA matching is very important, since these transplants are at high risk for graft rejection. On the other hand, for liver transplants, HLA mismatches have little impact on graft survival. Heart and lung transplants fall somewhere in between but minimizing HLA mismatches significantly improves survival. For liver, lung, and heart transplants, few donors are available and it is hard to get good HLA matches. Transporting and storing donated organs can take time. The "best" match may live many miles from the "ideal" recipient. The need to have the "best" matches must be balanced against the time it takes to procure and transport a donated organ and then transplant it.
The nurse is alerted to possible anaphylactic shock immediately after a patient has received IM penicillin by the development of
edema and itching at injection site, A systemic anaphylactic reaction starts with edema and itching at the site of exposure to the antigen. Shock can rapidly develop with rapid, weak pulse; hypotension; dilated pupils; dyspnea; and possible cyanosis.
A patient is undergoing plasmapheresis for treatment of systemic lupus erythematosus. The nurse explains that plasmapheresis is used in treatment to
exchange her plasma that contains antinuclear antibodies with a substitute fluid.
Nurses should approach families of actively dying patients to ask if they would be interested in organ donation
false
Mycophenolate mofetil
inhibits purine synthesis with suppressive effects on T and B cells. The major limitation of this drug is GI toxicity, including nausea, vomiting, and diarrhea. In many cases the side effects can be lessened by lowering the dose or giving smaller doses more often. - IV only reconstituted in D5W, don't give as an IV bolus, give over 2 hrs
living organ donors
may be directed, non-directed, paired-exchange, or - In cases of directed living organ donation, the donor specifically chooses who will receive the transplant. Example: a man donates a kidney to his sister. - In cases of non-directed living organ donation, the donor is not related to the recipient and does not know the recipient. The donor is making a gift out of selfless reasons, and the organ is matched to a recipient using UNOS. - In cases of paired-exchange living organ donation, at least two donor-recipient candidates with incompatibility "trade" organs with a compatible pair.
deceased organ donor
meet criteria for donation by: Donation after Brain Death (DBD) or Donation after Circulatory Death (DCD). - Donation after Brain Death (DBD) donors have suffered a catastrophic brain injury, and brain death criteria has been met. Brain death is death from both a clinical and a legal perspective - Donation after Circulatory Death (DCD) donors are unlikely to progress to brain death, but have a poor prognosis. In these situations, the family has already decided to withdraw life support before approaching donation.
Urinary cath:
regulate IV fluids according to output, connect indwelling catheter lower than bed to promote drainage, remove cath within a few days post op, implement continuous bladder irrigation as prescribed to remove blood clots that can obstruct the indwelling catheter and cause damage to donor kidney. Three risks to catheterize: oliguria, infection from an indwelling urinary catheter, and blood clot formation. Reasons for an indwelling urinary catheter- monitor hourly urinary output, color of urine, and clots.
immunosuppressive therapy
requires a lifelong balance between rejection and infection. On 1 hand, the immune response must be suppressed to prevent rejection of the transplanted organ. On the other hand, an adequate immune response must be maintained to prevent overwhelming infection and the development of cancers. Many of the drugs used to achieve immunosuppression have significant side effects. Because transplant recipients must take immunosuppressants for life, the risk for toxicity continues for the rest of their lives. With the use of a combination of agents that work during different phases of the immune response, we can give lower doses of each drug to produce effective immunosuppression while minimizing side effects. The major immunosuppressive agents are (1) calcineurin inhibitors; (2) corticosteroids (prednisone, methylprednisolone); (3) purine synthesis antagonists, including mycophenolate mofetil (CellCept, Myfortic) and azathioprine (Imuran); and (4) sirolimus. Muromonab-CD3 (Orthoclone OKT3) and either horse antithymocyte globulin (Atgam) or rabbit antithymocyte globulin (ATG) are IV medications used for short periods to prevent early rejection or reverse acute rejection. Immunosuppression protocols are highly variable among transplant centers, with different combinations of medications being used. Most patients are initially on triple therapy. The standard triple therapy usually includes a calcineurin inhibitor, a corticosteroid, and mycophenolate mofetil. The doses of immunosuppressant drugs are reduced over time after the transplant. The trend in many transplant centers is to follow an immunosuppression protocol that uses minimal corticosteroids because of their many side effects. Patients taking corticosteroids may be weaned off after a few years.
Patient has an hgb of 8.2 g/dL and hct of 28% + reciving a transfusion of PRBCs. Client reports back pain, chills, fever during. Priority nursing action?
stop transfusion. The patient is having a transfusion reaction and the transfusion should immediately be stopped. Vital signs are taken, and medications administered to counteract the reaction. The blood should be saved for testing. The provider may be called after the transfusion is stopped. The patient should be monitored after the transfusion is discontinued until the condition is stable. After the transfusion is discontinued and the reaction is terminated, the back pain, fever, and chills will cease, and the acetaminophen will not be required.
organ transplantation
success has improved with advances in surgical technique, advances in histocompatibility testing, and more effective immunosuppressant drugs. Common tissue transplants include corneas, skin, bone marrow, heart valves, bone, and connective tissues. Cornea transplants can prevent or correct blindness. Skin grafts are used in managing burn patients. Donated bone marrow can help patients with leukemias and other cancers. Transplanted organs currently come from many different body systems. These organs include the heart, lung, liver, kidney, pancreas, and intestine. Multiple organs can be transplanted together, such as kidney and pancreas, kidney and liver, kidney and heart, or the complete intestinal tract. For example, some patients with diabetes who receive a pancreas transplant also receive a kidney transplant because the diabetes has not only impaired the pancreas but also led to renal failure. Some organs can be transplanted in parts or segments instead of transplanting an entire organ. Liver and lung lobes (rather than the whole organ) may be transplanted, or an intestine may be used in segments, thus allowing for 1 person's organ donation to help many recipients. This technique enables living donors to donate part of an organ or 1 of their organs, in the case of kidneys. Organ donations come from either deceased (cadaver) or living donors. Most organs and tissues currently come from deceased donors. However, because of the shortage of organs from deceased donors, the use of related and living unrelated donor organs is increasing.
corticosteroids mechanism of action
suppress inflammatory response, inhibit cytokine production (IL-1, IL-6, TNF) and t cell activation and proliferation.
Nurses are involved in various steps of the organ donation process
true
monoclonal antibodies
used to prevent and treat acute rejection episodes. Muromonab-CD3 was the first of these monoclonal antibodies to be used in clinical transplantation. It is a mouse monoclonal antibody that binds with the CD3 antigen found on the surface of human thymocytes and mature T cells. It interferes with the function of T cells, the pivotal cells involved in rejection. All T cells are affected, rather than just the subset active in graft rejection. It is given by IV bolus. Within minutes after the first infusion of muromonab-CD3, the number of circulating T cells decreases significantly. A flu-like syndrome occurs during the first few days of treatment because of cytokine release. Side effects include fever, rigors, headache, myalgias, and various GI disturbances. To reduce the expected side effects of muromonab-CD3, give patients acetaminophen, diphenhydramine, and IV methylprednisolone beforehand. Newer generation monoclonal antibodies are a hybrid of mouse and human antibodies and have fewer side effects than muromonab-CD3 because they have been "humanized." These include daclizumab (Zenapax) and basiliximab (Simulect), which target the IL-2 receptor and impair lymphocyte proliferation. Another monoclonal antibody is alemtuzumab (Campath), which targets the CD52 antigen found on T and B cells, monocytes, and macrophages. It can cause prolonged T-cell depletion.
client presentation of end stage kidney disease
◦ Anorexia ◦ Fatigue ◦ Numbness and tingling of extremities ◦ Shortness of breath ◦ Dry, itchy skin ◦ Metallic taste in the mouth ◦ Muscle cramping ◦ Decreased attention span ◦ Seizures ◦ Tremor ◦ Heart failure ◦ Edema of hands and feet ◦ Dyspnea ◦ Distended jugular veins ◦ Anemia ◦ Vomiting ◦ Pulmonary edema ◦ Hypertension ◦ Cardiac dysrhythmias ◦ Pallor ◦ Bruising ◦ Halitosis ◦ Diminished or dark-colored urine
Indications of end stage kidney disease
◦ Anuria ◦ Proteinuria ◦ Marked azotemia (elevated blood urea nitrogen (BUN) and blood creatinine) ◦ Severe electrolyte imbalance (hyperkalemia, hypernatremia) ◦ Fluid volume excess conditions (heart failure, pulmonary edema) ◦ Uremic lung
post transplant nursing actions
◦ Assess vital signs every 15 min initially and advance to every hour (follow institutional protocol). Maintain blood pressure within prescribed parameters. ◦ Assess intake and output at least hourly. Urine output should be greater than 30 mL/hr. Notify the provider of oliguria evidenced by urine output less than 30 mL/hr. ◦ Monitor for abrupt decrease in urine output, indicating rejection, tissue injury, thrombosis of the renal artery, or obstruction in the renal system. ◦ Assess urine appearance and odor hourly (initially pink and bloody, gradually returning to clear in a few days to several weeks). ◦ Monitor daily urinalysis to check for protein, WBCs, RBCs, ketones, glucose, specific gravity, and pH. ◦ Daily weight assists in monitoring fluid status. ◦ Monitor for fluid and electrolyte imbalances (hypervolemia, hypovolemia, hypokalemia, hyponatremia). ◦ Monitor for manifestations of infection (dyspnea, fever, incisional drainage, redness). ◦ Monitor for early manifestations of organ rejection (fever, hypertension, pain at the transplant site). ◦ Assess surgical dressing for bloody drainage, which can indicate hemorrhage or hematoma formation. Administer intravenous fluids as prescribed, usually calculated to replace hourly urine output. ◦ Administer oral fluids and discontinue IV fluid once bowel function returns and fluids are tolerated. ◦ Provide urinary catheter care. ◦ Attach the large indwelling urinary catheter to dependent bedside drainage. ◦ Maintain continuous bladder irrigation as prescribed to prevent obstruction from blood clot formation, which can cause damage to the transplanted kidney. ◦ Remove the urinary catheter as soon as possible to decrease the risk of infection. ◦ Intervene for oliguria as prescribed. Diuretics and/or dialysis can be necessary until kidney function is satisfactory. ◦ Mannitol, an osmotic diuretic, preserves urine flow and reduces the risk of acute kidney injury. Filtered mannitol draws water into the nephrons of the kidney and promotes diuresis. ◦ Thiazides and loop diuretics are less effective when filtration rate is lower, causing less diuresis. Monitor for excessive diuresis, which can result in hypovolemia and hypotension, and cause reduced blood flow to the graft. Notify the provider immediately. ◦ Administer immunosuppressive medications to prevent rejection (corticosteroids, cyclosporines, or other prescribed medication, and monoclonal antibodies [basiliximab or daclizumab]). ◦ Monitor for complications (infection, hypovolemia, fluid retention). ◦ Immediately notify the surgeon if any manifestations of organ rejection appear. ◦ Administer stool softeners to prevent straining and constipation (risk associated with bowel manipulation during abdominal surgery and the effects of general anesthetics and analgesics). ◦ Arrange for counseling for the client and family if necessary. ◦ Arrange for post-transplant follow-up appointments and interventions. client ed: Monitor and report manifestations of infection (fever, incisional drainage, redness). ◦ Adhere to the pharmacological regimen (corticosteroids, antilymphocyte preparations, cyclosporine, monoclonal antibodies). ◦ Adhere to the prescribed diet and activity level. ◦ Turn, cough, and deep breathe to prevent atelectasis and pneumonia.
activity recommendations post transplant
◦ Avoid contact sports that can cause an injury to the transplanted kidney. ◦ Increase activity as tolerated.
cause of chronic rejection
◦ Blood vessel injury from overgrowth of the smooth muscles of the blood vessels causing fibrotic tissue to replace normal tissue, resulting in a nonfunctioning donor kidney
Findings in hyperacute rejection
◦ Fever, hypertension, pain at the transplant Site
nursing actions infection
◦ Give high priority to infection control measures, such as frequent hand hygiene. ◦ Monitor for and report manifestations of a localized (wound) or systemic infection (pneumonia, sepsis).
infection
◦ Infection is a common cause of first-transplant-year morbidity and mortality. Detection of early manifestations of infection are difficult when the client receives immunosuppressive therapy. Vague manifestations include low-grade fevers, mild reports of discomfort, and mental status changes.
treatment acute rejection
◦ Involves increased doses of immunosuppressive medications
diet recommendations post transplant
◦ Low-fat to decrease cholesterol ◦ High-fiber to avoid constipation ◦ Increased protein to promote healing, and rebuild and maintain muscle mass ◦ Adequate intake of potassium, calcium, and phosphorus ◦ Restricted sodium intake to prevent fluid retention and hypertension especially when taking prednisone ◦ Avoidance of concentrated sugars or carbohydrates to control glycemic factors when on prednisone Magnesium supplements because cyclosporine can reduce magnesium levels ! Avoid grapefruit, which causes increased cyclosporine blood levels, when taking cyclosporine.
nursing actions thrombosis
◦ Monitor for and report a sudden decrease in urine output. ◦ Prepare the client for emergency surgery requiring an emergency transplant nephrectomy (removal of the transplant kidney).
nursing actions renal artery stenosis
◦ Monitor for and report hypertension, bruit over artery anastomosis site, and decreased kidney function, such as oliguria and elevated BUN and creatinine. ◦ Prepare the client for a kidney scan to verify the status of renal blood flow. ◦ Angioplasty and/or surgical intervention might be necessary.
client education infection
◦ Monitor for and report manifestations of infection (fever, incisional drainage, redness). Later indications of infection can include fatigue and discomfort. ◦ Due to increased risk for infection during immunosuppressant therapy, perform infection control measures (frequent hand hygiene, avoiding crowds and people who have a communicable disease). Consider wearing a face mask when out in public. Adhere to the pharmacological regimen.
client education of chronic rejection
◦ Monitor for manifestations of rejection and contact the provider immediately. ◦ Rejection is diagnosed through a kidney scan and kidney biopsies. ◦ Adhere to the pharmacological regimen.
nursing actions ischemia
◦ Monitor urine output, blood creatinine, and BUN levels to detect failure of the transplanted kidney. ◦ Report hourly output volumes less than 30 mL/hr. Assist the client with dialysis as indicated. • Prepare the client for a kidney biopsy to distinguish ischemia from organ rejection.
findings acute rejection
◦ Oliguria, anuria, low-grade fever, hypertension, tenderness over the transplanted kidney, lethargy, azotemia, and fluid retention
client education nursing transplants
◦ Prepare mentally and emotionally for the procedure. ◦ The interprofessional transplant team is involved in the procedure. This includes nurses, provider, transplant surgeon, anesthesiologists, nephrologists, clinical nurse specialist, and other interprofessional health care workers. ◦ Adherence with the post-transplant interventions (lifelong immunosuppression) and risk factor reduction (smoking cessation, blood pressure and blood glucose control) are crucial to the success of the transplantation.
lab data end stage kidney disease
◦ Proteinuria ◦ Hematuria ◦ Elevated BUN levels ◦ Elevated blood creatinine -Decreased glomerular filtration rate, either estimated from blood or urine creatinine 24-hr values ◦ Decreased hemoglobin and hematocrit ◦ Elevated potassium and phosphorus levels ◦ Sodium within expected reference range, increased, or decreased Metabolic acidosis
nursing actions for kidney transplants
◦ Schedule preoperative laboratory assessments, including blood chemistry studies, CBC and differential, bleeding times, urine culture, blood type, and crossmatch. ◦ Administer preoperative medications as prescribed. ◦ Prophylactic antibiotics ◦ Immunosuppressant therapy ◦ Corticosteroids decrease the immune system response of inflammation and rejection of the donor kidney. ◦ Cyclosporine, azathioprine: Immunosuppressant medications prevent rejection of the donor kidney. ◦ Mammalian target of rapamycin (mTOR) inhibitors interrupt the stimulation of T-cell signals. ◦ Everolimus prevents activation of B cells and T cells to prevent rejection of the donor kidney. ◦ Monoclonal antibodies: Basiliximab or daclizumab are antibodies that bind with T cells to reduce T-cell growth and activation at the receptor site to prevent rejection of the donor kidney.
pre kidney transplant
◦ To increase the chance of graft survival, blood from the live kidney donor is often transfused into the client receiving the transplant. ◦ The client usually receives dialysis within 24 hr of surgery.
client education thrombosis
◦ Understand the risk of a blood clot. ◦ Inform the provider of a sudden decrease in urine output.
