Surgery Medical School Crash Course (Unabridged) - 07 A_T_F

This chapter focuses on transplant surgery and the immunological challenges faced by transplant patients. Liver transplantation is considered a last resort for patients with acute liver failure, primary hepatic cancer, or end-stage liver disease. However, it rarely cures the underlying disease, with recurrence occurring in most patients. The major indications for liver transplant include acute liver failure, cirrhosis with complications, certain liver cancers, and liver-based metabolic problems. Evaluation for a liver transplant involves assessing the patient's ability to tolerate the surgery, their immunological status, and the demands of post-transplant care. Various tests are conducted to determine the patient's suitability for a transplant, including heart and lung evaluations, screening for infections and cancers, and psychiatric testing. Patients with certain conditions, such as severe heart or lung disease, uncontrolled sepsis, or lack of social support, may be ineligible for a Chapter 4, Transplantation and Immunology. This chapter is primarily devoted to transplant surgery and the immunological problems faced by the patient who has a transplant. The care of the transplant patient involves both the evaluation of their ability to withstand a transplant and the management of their immunological difficulties associated with keeping the transplant viable. Overview of Liver Transplantation. Liver transplantation is an important option for patients who have acute liver failure, a primary hepatic cancer, or end-stage liver disease. It is considered a last resort after all other medical treatments have failed. The biggest problem with liver transplantation is that it rarely cures the underlying disease, with recurrent disease occurring in up to 100% of patients, depending on what the transplant is for. This means that the risk versus benefit must be evaluated prior to doing this kind of procedure. In most cases, unfortunately, the risk of the procedure does not outweigh the benefits of having it done. The major indications for liver transplant include acute liver failure, cirrhosis with systemic complications, certain liver cancers, and liver-based metabolic problems that have systemic manifestations. Patients with acute liver failure have the highest priority for liver transplant over patients with other liver problems. Patients with acute liver failure may recover without transplant, but most die within a few days if not given a liver transplant, as it can't be shown which patients will live and which will die. A liver transplant is indicated for all patients with acute liver failure. The definition of acute liver failure is the development of severe acute liver injury with some degree of encephalopathy and an impairment of the synthetic activity of the liver, such as having an INR, international normalized ratio, of greater than 1.5, without pre-existing liver disease. The time course that differentiates acute liver failure versus chronic liver failure is about 26 weeks. The main causes of acute liver failure are drug-induced hepatitis and viral hepatitis. Having cirrhosis alone is not enough to indicate the need for a transplant. Transplantation is indicated when the patient has portal hypertension or severely compromised liver function. Other findings associated with advanced cirrhosis include ascites, portal hypertension, and hepatic encephalopathy. When these things happen, the patient's likelihood of dying is high, and liver transplantation is warranted. Hepatorenal syndrome is a particularly bad complication of liver failure and indicates the urgent need for a transplant. There is a model for end-stage liver disease, or MELD, that is used to identify those patients with cirrhosis who might need a transplant. A MELD score of greater than 15 indicates the need for a transplant, although patients with childhood cirrhosis and portal hypertension should have a liver transplant even if their MELD score is low. When the MELD score reaches 10, the patient is referred for transplant, giving time to find a suitable donor before the patient gets too sick for a transplant, and the patient may have irreversible encephalopathy if they get sicker from their liver disease. Patients may also be candidates for a liver transplant if they have a complication that isn't included in the MELD scoring analysis. These include patients with hepatocellular cancer, hepatopulmonary syndrome, familial amyloid polyneuropathy, portopulmonary hypertension, cystic fibrosis, hilar cholangiosarcoma, hepatic artery thrombosis, or pulmonary hyperoxyluria. Patients may have complex medical conditions related to having liver disease that don't qualify for MELD testing. Other patients who qualify for transplanted livers include those with recurrent cholangitis, refractory ascites, intractable itching from primary biliary cirrhosis, portal hypertensive gastropathy with chronic blood loss, refractory variceal bleeding, and refractory hepatic encephalopathy. Patients with primary liver cancer may be candidates for a transplant if the lesion is less than 5 cm or up to 3 separate lesions less than 3 cm. They must have no evidence of blood vessel invasion and should have no regional or distant metastases. Certain neuroendocrine tumors that have metastasized to the liver may be candidates for transplant under certain circumstances. Certain liver-based metabolic problems that have systemic issues may be treated with liver transplantation. Patients with Wilson disease and alpha-1 antitrypsin deficiency can be cured with a liver transplant, but may have irreversible systemic problems if the transplant happened too late in the course of the disease. Some glycogen storage diseases can be treated with liver transplant as well as hemochromatosis and acute intermittent porphyria. There are multiple contraindications for liver transplant. These include having severe heart or lung disease, acquired immunodeficiency syndrome, cancers outside of the liver, metastatic liver cancer, intrahepatic cholangiosarcoma, hemangiosarcoma, uncontrolled sepsis, anatomic problems that preclude a successful transplant, elevated intracranial pressure, lack of adequate social support, or an inability to follow post-transplant medical treatment. Patients with alcoholic liver disease are required to be abstinent from alcohol for a minimum of 6 months and must be partaking of a structured alcoholic rehabilitation program. They need adequate social support to help them sustain their sobriety. Patients with alcoholic hepatitis not expected to live longer than 6 months are sometimes transplanted, but this is rare. Patients older than 65 years of age are not transplanted, regardless of their liver problem. Patients with a body mass index of greater than 40 have worse transplant outcomes after liver transplant, so some transplant centers will not transplant these patients unless they lose weight before the transplant surgery. Some patients will have a gastric bypass or gastric sleeve surgery before their liver transplant to help them lose enough weight for their liver transplant. Evaluation for liver transplant. The goal of pre-transplant evaluation is to see if the patient can tolerate the surgical stresses involved in liver transplants, their immunological status, and the demands of the care it takes to have a liver transplant. Each patient needs a thorough heart and lung evaluation, screening for cancers or occult infections, and psychiatric testing. The patient's medical history is reviewed and further tests are done if the initial screening tests are abnormal. Lab testing done include ABO and RH blood typing, liver function testing, CBC with differential, creatinine clearance, calcium level, vitamin D level, serum alpha-fetoprotein level, testing for liver viruses, varicella virus, HIV, cytomegalovirus, syphilis and Epstein-Barr virus, urinalysis, and a urine drug screen for illicit drugs. The heart and lungs are tested for coronary artery disease, valvular diseases of the heart, obstructive or restrictive lung disease, cardiomyopathy, hepatopulmonary syndrome, and pulmonary hypertension. Some of these tests will exclude the patient from being a liver transplant candidate, while other tests indicate the need for some type of treatment that will make the patient a better transplant recipient. Noninvasive cardiovascular testing is done for all patients greater than 40 years of age and for younger patients with risk factors for heart disease. Blood gases are obtained from all patients as well as pulse oximetry. Pulmonary function testing is done on all patients and a chest x-ray is obtained. If the patient has only mild or moderate pulmonary hypertension, they are still candidates for having a transplant. An electrocardiogram is done for ischemia and arrhythmias and cardiac stress testing is done by all patients over 40 and all patients with cardiac risk factors. If stress testing is abnormal, a cardiac catheterization is obtained and the patient is treated for any blockages before having a liver transplant. An echocardiogram is done on high-risk patients to look for portopulmonary hypertension and valvular diseases of the heart. If patients are suspected of having hepatopulmonary syndrome, they will have a contrast enhanced echocardiogram. Pulse oximetry is done on all patients as a screening tool for hepatopulmonary syndrome. If they have the disease, they will have liver disease, low oxygen concentrations and intrapulmonary vascular dilations of the pulmonary vasculature. They have a worse prognosis than patients with cirrhosis and if their pulse oximetry is less than 96 percent, they need arterial blood gases drawn and a transthoracic contrast enhanced echocardiography. Some patients will have a chest computed tomography or CT scan to evaluate their lungs. Cancer screening involves doing a CT scan or magnetic resonance imaging or MRI exam of the abdomen to look for liver cancer and a skin evaluation to look for skin cancer. Patients over 50 years of age or who have primary sclerosing cholangitis will have a breast screening colonoscopy. Breast cancer screening, cervical cancer and prostate cancer need to be done depending on the patient's age and gender. Serologies for various viruses are obtained and a skin test for tuberculosis should be done. If the skin test is positive for tuberculosis, the patient may need to be treated for the disease before getting a transplant. Any dental extractions necessary should be done before the transplant. Vaccination should be given for hepatitis A, hepatitis B, influenza, tetanus, pertussis, diphtheria and pneumococcus. Hepatic imaging needs to be undertaken to see what the hepatic vasculature is like and to see if the patient can successfully be transplanted. Patients with hepatocellular cancer should have hepatic imaging to stage the disease. The screening can involve a contrast-enhanced CT scan or a contrast-enhanced MRI examination. Upper GI endoscopy should be done in patients who have cirrhosis or portal hypertension to see what kind of esophageal varices they have. Bone density testing to screen for osteoporosis should be done with treatment given before the transplant. Men or women with osteoporosis should be given bisphosphonates but need to be given it with caution if they have esophageal varices as they can be made worse by the treatment. Osteopenic patients should have both calcium and vitamin D to build bone density. Psychosocial testing should be done to see if the patient is psychologically able to have a transplant and to see if they have social support. Education about transplantation should be done before the procedure to make sure the patient understands what is being done to them. If the patient lacks insight into their disorder or what the transplant involves, they may not be a suitable candidate for the procedure. Spouses and other loved ones should be part of the educational process. Patients with substance use problems involving drugs or alcohol should be treated before having a transplant as this will increase the success of the transplant. The treatment requirements depend on the transplant team but most centers require a period of sobriety before the transplant can be performed. Evaluation of the potential renal transplant recipient. A kidney transplant is the treatment of choice for most patients suffering from end-stage kidney disease. A successful kidney transplant can improve the patient's quality of life and can reduce the mortality risk for patients with kidney failure when compared to being on dialysis. Patients with end-stage kidney disease have many health problems. It is important for kidney transplant recipients to be carefully examined prior to a transplant to detect and treat the diseases associated for their co-existing illnesses as these can affect their ability to withstand the pressures of a transplant. Ideally, the pre-transplant evaluation should be as efficient and cost-effective as possible so the kidney failure patient can be adequately assessed for the possibility of having a life-saving transplant. Transplantation needs to be discussed with all patients who have irreversible and worsening chronic kidney disease. Patients interested in a transplant and who have no medical contraindications for surgery should be referred for transplantation when their glomerular filtration rate is less than 30 milliliters per hour. Although there are no kidney replacement options at this level of kidney failure, this referral will be early enough to allow for a complete evaluation and for interventions that may need to take place and to address any relative contraindications before a transplantation. These things can take time, and it may take a while to find an adequate donor for the transplantation. It can be hard to predict with accuracy the time it takes for kidney insufficiency to progress to kidney failure, so it is preferable to have a transplant candidate ready for a transplant as soon as their transplant becomes acutely necessary. Research has reported improved patient and graft survival when the patient gets their first transplant prior to needing dialysis, although this finding has not been found to be the case in patients who need a second transplant. The best time for a transplant is when the patient has their kidney transplant at the time when their renal function has deteriorated beyond a threshold level compatible with acceptable renal function. This absolute level isn't the same for every patient, but should represent a degree of kidney function not associated with already having uremia. Transplantation at higher levels of kidney function doesn't offer any benefits over having a transplantation with lower levels of kidney function. Previous guidelines suggest that the optimal level of kidney function for a transplant involves a glomerular filtration rate of less than 20 and when there is evidence of progressive deterioration of function over the most recent 6 to 12 months. An exception is made when the patient has both a kidney transplant and another type of solid organ transplant at the same time. In the United States, patients can begin being on the waiting list for a deceased donor waiting list when the glomerular filtration rate is less than 20 milliliters per minute or when they are on chronic dialysis treatments. Candidates for a combined pancreas and kidney transplant must also meet these qualifications. Pediatric patients with kidney failure must be listed before their 18th birthday to qualify for having pediatric priority. The initial evaluation of the potential kidney transplant recipient should involve a thorough surgical, medical, and psychosocial history as well as a complete physical examination. Things like a history of blood or platelet transfusion, pregnancies, and previous transplants must be assessed. Attention needs to be directed at the heart exam, the lung exam, the teeth, and the peripheral arterial pulses. A careful examination of the pelvis must be looked at for previous surgeries as the transplanted kidney will be placed in the patient's pelvis. The goal is to find any comorbidities that will affect the patient's survival after the transplant. The evaluation also determines if it is technically feasible to do the surgery and if the patient will be successful with post-transplantation immunosuppression. Any comorbidity that may otherwise shorten the patient's survival may render a patient not eligible to receive a kidney because the new kidney will not help the patient live any longer. There are unfortunately many reasons why an individual might be ineligible for a kidney transplant. There are specific clinical guidelines around the Western world that list the various eligibility criteria for patients needing a kidney transplant that include things like patient age, body mass index, and workup for heart and lung disease. The criteria are different from organization to organization, which make it difficult for potential transplant patients to decide where to go for kidney transplant evaluation. The general guidelines that indicate a person shouldn't have a transplant include having an active infection, cancer that has not been treated, substance abuse, reversible kidney disease, documented psychiatric disease, and ongoing treatment nonadherence. Patients who have a short life expectancy despite their kidney disease are also relatively contraindicated to have a kidney transplant as their short life expectancy makes it impractical to provide the patient with a kidney that won't prolong their life. The age of the recipient alone is not a contraindication to having a kidney transplant. With many patients aged 70 and older being good candidates for kidney transplant with acceptable long-term survival, patients over 65 represent 18% of deceased donor transplant recipients and 20% of living donor recipients. They need to have a life expectancy that exceeds the kidney transplant waiting time. Relative contraindications include malnutrition, active systemic diseases that have caused kidney failure, such as antineutrophil cytoplasmic antibody-associated vasculitis, systemic erythematosus, or primary oxalosis. Some places will exclude patients with hyperparathyroidism as well. Some patients can have excision of their parathyroid glands to be a candidate for a transplant. Patients with primary oxalosis may be candidates for a simultaneous kidney and liver transplant. Patients with systemic amyloidosis, especially disease that affects the heart, are not good candidates for kidney transplant as they have a high mortality rate. Screening for Kidney Transplantation. Patients needing a kidney transplant will have a blood type, Rh type, complete blood count, electrolytes, blood urea nitrogen level, creatinine, phosphorus, calcium, liver function studies, albumin level, partial thromboplastin time, protein, parathyroid hormone level, and hemoglobin A1c. Women of childbearing age need a pregnancy test. Serology is obtained for measles, varicella, rubella, and mumps. If they are found not to be immune to these childhood diseases, they are vaccinated for these diseases. Serology is also done for human immunodeficiency virus, HIV, hepatitis B, hepatitis A, and hepatitis C. While being positive for these viruses doesn't preclude having a kidney transplant, it does require further evaluation. A rapid plasma reagent or RPR is done for syphilis, while some centers also screen for toxoplasmosis, coccidioidomycosis, shagus disease, and histoplasmosis. Human leukocyte antigen or HLA testing is done to see if the patient has been sensitized against certain HLA types in the past. A urinalysis and 24-hour urine collection and urine culture are obtained, with serum and protein electrophoresis done to see what the cause of the kidney disease might be. A drug screen for alcohol and illicit drugs is also performed. Purified protein derivative or PPD testing is done for tuberculosis, and a chest X-ray is done to further evaluate a positive skin test. An electrocardiogram is done and an echocardiogram is performed. A thallium myocardium perfusion scan, dobutamine stress test, or angiogram may be done in high-risk heart patients. All men need a testicular exam, while men over 50 need a prostate-specific antigen or PSA test, and a digital rectal exam is performed to rule out prostate cancer. Women need a thorough breast exam and papunicolau smear, while women older than the age of 40 need a mammogram, unless they have a strong family history of breast cancer, in which case they should have a mammogram at 35 years of age or more. Colonoscopy screening is done on all patients greater than 50, and patients with Barrett's esophagus need an upper GI endoscopy to rule out esophageal cancer. Internal and pelvic ultrasounds are done to check the kidneys, ureters, and pelvic organs. Anti-A testing is done in patients with blood type B to see if they can receive a kidney from a patient with type A blood or type AB blood. Certain patients need further evaluation. Patients with known heart disease need evaluation of their heart, because the most common cause of death after a kidney transplant is cardiovascular disease. Patients with progressive angina that can't be treated with a bypass surgery or angioplasty, patients with a myocardial infarction within the past 3 to 6 months, and patients with severe coronary artery disease are relatively excluded from having a kidney transplant. In the same way, patients with cardiomyopathy and an ejection fraction of less than 30% are also relatively excluded from a kidney transplant, although some patients are candidates for a simultaneous heart and kidney transplant. It is crucial to first identify those patients who have reversible disease of either organ. Patients who have cardiomyopathy that isn't from ischemia and who have no other contraindications may be candidates for having a kidney transplant. Patients with heart disease that are not symptomatic, patients with negative non-invasive testing, and patients on medical therapy who have non-critical angiographic findings, and patients who have had successful interventions will be reasonable candidates for kidney transplant. In general, any patient with chronic kidney disease will have higher cardiovascular risk factors compared to patients without kidney disease. It isn't clear however that asymptomatic patients should be screened before their kidney transplant. All patients with angina, low ejection fractions, type 1 diabetes mellitus, or a positive non-invasive stress test are referred for angiography and further cardiac evaluation as they are automatically at high risk for coronary artery disease. A patient without angina, cardiomyopathy with a low ejection fraction, or diabetic neuropathy from type 1 diabetes may be screened further for heart disease if they are older than 60 years of age, hypertensive, have elevated blood sugars, hyperlipidemia, peripheral artery disease, previous myocardial infarction, left ventricular hypertrophy, family history of heart disease, long-standing dialysis, long-standing kidney failure, history of radiation therapy, or a smoking history. If they have less than 3 of these risk factors, no further screening is necessary. All patients with diabetes and peripheral vascular disease, however, are tested regardless of other risk factors. Patients with at least 3 of the above risk factors, diabetes or peripheral vascular disease, are screened with a dobutamine stress echocardiogram or a myocardial perfusion study. The actual test performed depends on the center that screens patients for heart disease prior to a transplant. Patients who test negative but still have risk factors are retested every 2 years before a transplant. Patients with evidence of heart failure are also evaluated further. They receive the basic history, physical, chest x-ray and electrocardiogram, but also have an echocardiogram with treatment of their heart failure before having a kidney transplant. Patients with pulmonary hypertension by echocardiogram need treatment before transplantation. Patients with left atrial dilation have been linked to poor transplant outcome. Patients with infections should be free of any active infection before transplantation. A PPD will check for tuberculosis and a chest x-ray will look for a cult infection. Patients with active tuberculosis need treatment before transplant. And patients with active dental infections will need treatment. Most centers will exclude HIV patients, while other centers will allow HIV patients to have a transplant. If they are on antiretroviral therapy, patients who test for viral serology need treatment or they may be excluded from having a transplant. In addition to identifying and treating active infections, patients at a high risk for infections need prophylaxis for certain types of infections. Patients considered at high risk include those with immunodeficiency diseases, immunosuppressive histories, chemotherapy patients, and patients with a splenectomy. Immunizations should be given for pneumococcus, hepatitis B, varicella, and influenza. Patients without a spleen should have meningococcus vaccinations and haemophilus influenzae vaccinations. Patients with peptic acid disease, colonic diseases, and cholelithiasis are at a higher risk for getting a kidney transplant. Contraindications to a kidney transplant include having active peptic ulcer disease, unless they are treated and have resolution of their ulcers. Patients with chronic liver disease and active hepatitis with hepatitis B and hepatitis C need referral to a hepatologist for a pre-transplant analysis. Those who already have fibrosis or cirrhosis of the liver based on a liver biopsy may not be suitable candidates for a kidney transplant and may need both a liver and a kidney transplant. Cholecystitis patients and patients with colonic diseases need further evaluation before having a transplant. Patients with diabetic nephropathy as a cause of their kidney disease need cholecystitis evaluation and possible treatment. Although removing the gallbladder before transplantation isn't routinely recommended, patients with polyps in the colon, diverticulosis, diverticulitis, inflammatory bowel disease, or a high risk for colon cancer need either a barium enema or a colonoscopy before being allowed to have a kidney transplant. Most of these patients can be treated before having their transplant. Older patients with high blood pressure, high cholesterol levels, and a smoking history should be carefully checked for carotid stenosis, which could lead to stroke before, during, or after their transplant. If carotid disease is found, these patients need to be treated before having a transplant. Patients with transient ischemic attacks as part of their history need to be cleared by a neurologist and should have Doppler ultrasound evaluation of their carotid arteries. Patients with autosomal dominant polycystic kidney disease who have a headache history or a family history of cerebral aneurysm need to have a magnetic resonance angiogram to look for aneurysms that need treatment before getting a transplant. Any aneurysm bigger than 7 to 10 millimeters must be treated before transplant surgery. Patients should have their femoral and pedal pulses evaluated carefully before getting a transplant. Patients who have severe iliac disease, cardiovascular disease, or untreatable peripheral vascular disease are not candidates for transplantation. A Doppler vascular study and CT scan of the abdomen and pelvis can be done to look for calcium deposits in the iliac arteries, which will determine where the transplanted kidney is placed. Many patients develop peripheral vascular disease after surgery to replace a damaged kidney, especially patients with diabetes. The risk for peripheral disease complications or amputation is about 6% after transplant surgery for all patients and about 20% among diabetic patients. These patients often face an amputation and poor patient survival. Having peripheral vascular disease involves having twice the risk of death when compared to patients without peripheral vascular disease in all transplant patients. Pulmonary disease may affect the success of the transplant. For this reason, patients who have heart failure symptoms or shortness of breath will have an echocardiogram to look for pulmonary hypertension. These patients are treated with diuresis or dialysis to see if the pulmonary hypertension improves. Short catheterization of the right heart should be done if the patient still has pulmonary hypertension. Severe pulmonary hypertension is linked to having a poor outcome after transplant. For this reason, they need to be treated with pulmonary vasodilator therapy. Lung patients that aren't candidates for a kidney transplant include those on home oxygen treatment, those with uncontrolled asthma, patients with core pulmonale or uncorrectable pulmonary hypertension, and patients with either chronic obstructive pulmonary disease COPD or restrictive disease that can't be treated. All patients who smoke should stop smoking as this can increase the risk of allograft loss and subsequent death after the transplant. Patients who stop smoking 5 years before transplant have an improved chance of allograft success. All patients need screening for cancer before transplantation. This is because the patient is to be immunosuppressed after the transplant, which will make cancer cells grow faster and will decrease the quality of the patient's life and will decrease their survival rate. Cancer screening involves a renal ultrasound, bladder cancer screening, thyroid cancer screening, and liver cancer screening. Patients with hepatitis B or hepatitis C are at a high risk for hepatocellular cancer and should have an alpha-fetoprotein level and liver imaging studies for cancer of the liver. Patients who have already had cancer should have a waiting period free of cancer for 2 to 5 years before being a suitable candidate for a kidney transplant. This is enough time for any micrometastases to develop and to make sure the patient doesn't have a recurrence as a result of immunosuppressive medications. The recurrence rate for cancer after transplantation is about 27%, but it depends highly on the cancer the patient had. Breast cancer with nodal involvement or inflammatory breast cancer needs to have a 5-year period of time without a recurrence before a kidney transplant, while carcinoma in situ requires a 2-year waiting period before getting a transplant. Five years' cancer-free intervals are necessary for patients with malignant melanoma, invasive cervical cancer, and advanced colorectal cancer. Patients with in situ bladder cancer, basal cell cancer of the skin, asymptomatic solid renal cancer, or squamous cell cancer of the skin do not need to have any waiting period. Patients with an abnormality of the lower urinary tract may not be candidates for kidney transplant. Voiding cystourethrogram is indicated in patients who have bladder dysfunction, recurrent bladder infections, reflux disease of the bladder, or pyelonephritis to make sure the excretion of the urine is normal as far as the lower voiding system goes. Patients with enlarged prostate glands and urethral stricture need to have these fixed to have a kidney transplant. Patients with a recurrent miscarriage, an arterial or venous thrombus, systemic lupus erythematosus, a thrombosis of a hemodialysis or fistula, an abnormal partial thromboplastin time, APTT, or an abnormal protime, PT, should be evaluated for having a hypercoagulable state that may require anticoagulation treatments around the time of their kidney transplant. Patients with bleeding tendencies or coagulopathic tendencies should have thorough coagulation studies, a hematology consult, and possibly a bone marrow biopsy. Patients found to have a monoclonal gammopathy with no known reason need to have a hematologist evaluation to make sure they don't have malignant myeloma before their kidney transplant. If malignant myeloma is excluded, the patient may have a transplant even if they have a monoclonal gammopathy. Patients who have end-stage kidney disease and who also have thrombocytopenia, hemolytic anemia, or some type of thrombotic microangiopathy should be evaluated to see if they have hemolytic uremic syndrome before getting a transplant. These patients can receive eculizumab to improve the chances of a graft survival. Patients with a body mass index of more than 30 kilograms per meter squared are at a higher risk for having an adverse outcome in getting a kidney transplant. Complications include delayed function of the new kidney, surgical complications such as poor wound healing and wound infection, as well as new-onset diabetes that occurs after getting the new kidney. Rejection rates are no different, and the rate of death is no different from the general population, however. Even so, weight loss is recommended before a kidney transplant in patients with extreme obesity and a body mass index of higher than 40 milligrams per meter squared. All patients should have a psychosocial evaluation to make sure they have no contraindicated behavioral issues, social issues, or financial problems that may influence their compliance with cares needed to maintain their transplanted kidney. Patients with alcohol or drug abuse need to go through treatment before having a transplant, and must remain free of drugs and alcohol for one year before becoming an active transplant list candidate. Some places also require tobacco abstinence, especially if there are heart disease risk factors. Marijuana use is contraindicated for a transplant. Some patients undergo neuropsychiatric testing to make sure they fully understand the risks and benefits of having a transplant and being on immunosuppressive drugs for the rest of their life. Patients with severe cognitive impairment may have a kidney transplant if they have caregivers that can supervise the giving of immunosuppressant drugs. Some patients with mood or anxiety disorders are referred for psychiatric treatment to improve the transplant success rate. Patients also need financial resources to pay for drug therapy after the transplant. Patients who are frail at the time of their transplant have a 94 percent increased risk of delayed grafted kidney function, a 61 percent risk of hospital readmission, and double the risk of death after a transplant. Sometimes a six-minute walk test, grip strength test, and a frailty score test is done to define those patients that will be successful after a kidney transplant. Having a previous kidney transplant is not a contraindication to having another kidney transplant. It should be understood, however, that these patients have a higher risk of re-transplant rejection rates the second time around. There is no minimum waiting list for patients needing a second or third transplant but those who are highly sensitized must wait longer for a cadaver kidney that won't be rejected. Some kidney diseases will, by nature of the disease, have the same problems with the transplanted kidney as they had with their original kidney. This is especially true of patients who have primary focal segmental glomerulosclerosis or FSGS. They have a 75 percent chance of losing their first kidney to recurrent disease and need a second or third kidney. The reason behind the patient's kidney failure should be determined as some kidney diseases will just come back when the transplanted kidney is given. This problem isn't a contraindication to getting a kidney but these patients need to be prepared for ongoing disease and probable graft failure over time. Patients with scleroderma, for example, are transplant candidates if the disease is suppressed and there is limited extrarenal involvement with the disease. A pre-transplant nephrectomy is not usually recommended at the time of the kidney transplant except in cases of polycystic kidney disease or recurrent nephrolithiasis with kidney infections secondary to kidney stones. Patients with polycystic kidney disease need a nephrectomy only if the size of their existing kidneys is very large. Those patients who need a nephrectomy do not have it at the same time as the kidney transplant but need to wait six weeks after the nephrectomy before having the kidney transplant to make sure there is no wound infection or postoperative complications. Transplantation Immunobiology. The human immune system is extremely complex and has been designed to respond to many diverse types of evolutionary stressors such as pathogens and other microorganisms. There is natural immunity that addresses specific non-immune responses and adaptive immunity which refers to a response to a specific known antigen that the patient was exposed to. In an organ transplant, the immune response to the graft is directed at the major histocompatibility complex molecules that are receptors on the donor's organ cells. This type of immune response comes from the adaptive immune system. Natural and Adaptive Immunity. The natural or innate immunity refers to the nonspecific parts of the immune system. In this system, there are macrophages, natural killer cells, neutrophils, the cytokine system, certain cellular receptors, and complement components that are directed at pathogens in things like physical damage to the tissues and the presence of pathogens that don't have an antibody yet associated with them. No antibody is required for this system to happen but they do have a robust immune response whenever foreign substances are introduced into the body. The adaptive immune system involves the recognition of specific antigens and is extremely specific to a particular antigen, making use of B lymphocytes and T lymphocytes. T cells can recognize the antigens produced by prior experience with the major histocompatibility proteins on donor organs. The B cells have immunoglobulin receptors that can recognize the antigens on pathogens or organ transplant tissues. Both the natural and adaptive immune systems are connected to one another. There is antigen-related T cell activation that leads to the production and secretion of chemokines and cytokines that are responsible for producing chemokines and cytokines which recruit aspects of the natural immune system and the adaptive immune system, producing activation of cellular or T cell immunity. An example of adaptive immunity that involves a person's B cells that allow for transplantation involves the ABO antigens on all cells of the body. In the past, it was necessary that the recipient and donor have the same ABO type or the recipient would reject the transplanted tissue. Now there are desensitization protocols using plasmapheresis and possibly a splemectomy combined with immunosuppressive regimens that are given after the transplant to remove these antibodies from T cell recognition. The role of antibodies that target non-human leukocyte antigen or HLA antigens on solid organs have long been implicated in the immune response. Patients generally need an HLA compatible kidney to have the best chance of not rejecting the organ. However, the risk of rejection is still high with patients having glomerulitis and peritubular capillary inflammation in the rejected transplanted organ. The biggest problem with rejection of an organ is the activation of T cells. T cell recognition of an antigen is the major event that initiates the immune response. The T cell receptor has the antigen presented to it and it attacks the organ with that antigen on it. There is T cell mediated cytotoxicity directed at the organ and more antibodies are made by the B cells. Macrophages also become involved in a delayed type hypersensitivity reaction. The Major Histocompatibility Complex or MHC. The MHC is a region of highly specialized genes localized on the 6th chromosome in humans. The protein products of these genes are expressed on the surface of many cells of the body. These are the principal antigenic proteins involved in graft rejection. Antibodies that are transplanted in MHC antigen mismatched individuals will be invariably rejected unless the patient is taking an immunosuppressant drug. MHC molecules represent a major part of the immune system as they provide the means for displaying antigenic peptides to the recipient's T cells. T cells are made in the thymus and have an affinity for the MHC complex so that they bind to antigenic peptides related to the MHC complex. There are two classes of MHC molecules which are class 1 and class 2. The structures of antigen presenting MHC class 1 and class 2 molecules are closely alike. They each contain a beta pleated sheet that supports two alpha helical regions forming a groove that contains the peptide antigen. There is a great deal of sequence homology between individuals with two different MHC genes. The alpha helical regions, however, are more variable from person to person. These are the receptors that identify a certain organ tissue cell as belonging to a specific MHC type. MHC class 1 and MHC class 2 molecules are different in their structure and the way they are expressed on the cells as well as the way they present themselves as antigens to the recipient's T cells. Class 1 MHC molecules consist of two separate polypeptide chains. MHC encoded alpha chain which is divided into three different domains and non-MHC components. Two of the MHC encoded alpha chain domains together form the antigen presented to the T cell. Class 2 MHC molecules are alpha beta heterodimers made from non-covalently associated polypeptide chains and are similar in structure. There is an antigen binding region of the class 2 molecules that are like those seen in class 1 MHC antigens. They are also recognized by the T cells of the recipient's immune system. The immune response that develops in response to donor tissue is primarily directed against the MHC proteins which are the major proteins. There are mild histocompatibility antigens that can also lead to allograft rejection. The rate of rejection of these minor proteins are less than is seen with the major histocompatibility proteins. The minor antigens play a role in graft versus host disease. In this setting, the donor MHC proteins that are identical to that of the recipient proteins present minor antigens in the context of self-MHC, thereby enhancing the GVH response. T cell recognition of the alloantigen is the primary and central event that leads to the cascade of events that result in rejection of a transplanted organ. Single T cells are monospecific in that they only recognize a single peptide presented in the context of the major histocompatibility complex. They activate cytokines which allow for the rejection response. There is a direct pathway in which host T cells recognize intact allo-MHC molecules on the surface of the donor or stimulator cell. Since the MHC molecules not bound to peptides are unstable and are not recognized by T cells, peptides that come from endogenous proteins that are bound to the groove of the donor MHC play a crucial role in this mode of allo-recognition. Direct allo-recognition by T cells of intact MHC molecules has not been demonstrated outside of alloimmunity, so it is a phenomenon that uniquely distinguishes alloimmunity from ordinary immunity to microorganisms. This pathway is thought to be the dominant pathway involved in the alloimmune response, as the number of T cells that proliferate on contact with allogenic or donor cells is extremely high compared to the number of clones that target antigen presented by the self-antigen presenting cell. What this means is that allo-recognition is of major importance in acute allo-rejection. The transplanted organ carries a variable number of APCs in the form of interstitial dendritic cells. These antigen presenting cells have a high density of allo-MHC molecules and are capable of directly stimulating the recipient's T cells. There is an indirect pathway in which T cells recognize processed allo-antigen presented as peptides by self-APCs. The basic premise for indirect allo-recognition as a mechanism involved in allograft rejection is that donor MHC molecules are shed from the graft and are taken out by recipient AOCs and then presented to T cells. In the setting of organ transplantation, peptides corresponding to polymorphic regions of the MHC induce a strong alloimmune response, whereas polymorphic peptides fail to induce this type of response. Whether a given section of MHC is immunogenic depends upon its amino acid sequence and on the structure of the MHC molecules in which it is presented. There is an increasing interest in the indirect pathway as peptide antigens are relatively simple structures that can be easily synthesized. This novel experimental approach permits the investigation of the molecule mechanisms of allograft rejection, which has led to many important findings. Allopeptide-reactive T cells are present during both acute and chronic rejection. Although the primary immune responses are characterized by T cell proliferative peptides that used to be immunologically silent, T cell co-stimulation implies that T cells require two separate signals to become activated. The first signal is antigen-specific and is provided by the engagement of the T cell receptor with peptide complexed with the major histocompatibility complex on the antigen-presenting cell. The second signal is provided by the interaction of one or more T cell surface receptors with their specific ligands on the antigen-presenting cell surface. There have been several additional T cell co-stimulatory pathways that have been discovered. Some of these pathways are important in activating effector T cells in transplant models. Naive T cells are made and matured in the thymus. These T cells wander within the blood and lymphocyte circulation. They preferentially leave by means of lymph nodes when an antigen is encountered. This causes T cell activation and a cascade of events that amplify the immune response. Once activated, the T cells enter the cell cycle and express a variety of cell surface proteins that mediate adhesion to other cells and matrix proteins. The changes result in an increase in the number of activated antigen-specific T cells that are more adherent to the accessory cells, in particular, endothelial cells. In addition, antigen-nonspecific T cells may also be activated and recruited into a rejection lesion when the level of inflammation is high. Leukocyte migration from the circulation to a site of inflammation, such as occurs in transplant rejection, includes four steps. These are rolling, which is select and mediated, triggering, which is chemokine-mediated, firm adhesion, which is integrin-mediated, and transmigration, which is mediated by platelet endothelial cell adhesion molecules and cytokines. Cytokines and chemokine receptors attract leukocytes to sites of tissue injury, infection, or allotransplantation, which is crucial for the induction of the acute inflammatory response. This process is controlled by a group of low-molecular-weight chemoattractant cytokines, or chemokines. More than 40 chemokines have been identified and have been divided into families based on the structural location of cysteine residues within the protein. The clear majority of chemokine proteins in the human immune system are made from only single chains of amino acids that contain four cysteine components that link together to form two disulfide bonds. The biggest families of chemokines are the alpha and beta varieties. The alpha chemokine family is made of cysteine molecules that are separated by a single amino acid, while the beta chemokine variety has adjacent cysteine molecules. Chemokines are tethered to the cell membrane by glycosaminoglycans, particularly chondroitin sulfates and heparin. Transplantation Rejection Issues A normal transplantation involves the action of taking cells, tissues, or organs from one individual to another. For example, there can be a transplantation of kidneys, hearts, lungs, livers, or pancreases from a donor to a recipient. The main barrier to transplantation is the immune system, which has a complex and effective way of combating foreign antigens. Unfortunately, these mechanisms are also involved in the rejection of transplanted organs, which are seen as foreign substances by the recipient's immune system. As a transplant surgeon, the understanding of these immune mechanisms is crucial, as it helps understand the clinical findings seen in rejection and helps make an early diagnosis of transplant rejection. There are fortunately new drugs and therapies that blunt the immune system's response to transplanted organs, so there is a prolonged survival of these organs. The degree of the immune response to a tissue or organ depends on the degree of genetic differences between the grafted organ and the host. Xenografts, which involve the transplantation of an organ or tissue between different species, have the greatest disparity and the highest potential to have an extreme immune response and rapid rejections. Autografts, which involve the transplantation of an organ or tissue from a part of the body to another part in the same individual, such as skin grafting, do not involve any type of foreign tissue transplantation and there is no chance of rejection. Isografts, which involve transplantation between identical twins, also have no risk of rejection. Allografts involve grafting of organs or tissues between members of the same species, but the grafts differ in their genetic makeup. These are the most common forms of transplantation. The degree to which these types of grafts are rejected depends on the similarities and differences in the MHC antigens on the tissue cells. Certain donor sites, such as the brain and the eye, are extremely easy to transplant as they have no immune cells associated with them and can tolerate grafting among mismatched individuals. Skin grafts have little vascularization, so they don't become rejected until they develop a blood supply. On the other hand, the heart, kidneys, and liver are highly vascular organs and will lead to a major cell-mediated response in the recipient. As mentioned, the main antigens responsible for rejection of organs and tissues are the histocompatibility antigens, which are the products of histocompatibility genes. These antigens are coded for on more than 40 locations on the chromosomes. However, only a few antigens are the primary antigens involved in rejection, which are the major histocompatibility, or MHC, complex antigens. The human MHC is known as the human leukocyte antigen, or HLA system, located on the short arm of the sixth chromosome. There are other antigens that can cause rejection, but it takes combinations of several of these antigens to create an immune response. The MHC genes are codominant, which means that each gene is expressed equally without the presence of dominant or recessive genes. There are two haplotypes in each individual, with one haplotype received from the mother and one haplotype received from the father. This makes the person halfway compatible with each parent, and a 25% chance that the organ donor recipient will have an identically matched HLA sibling. The two classes of MHC molecules are class I and class II. Class I molecules are found on all nucleated cells of the body, whereas class II molecules are only found on professional antigen-presenting cells, or APCs, including activated macrophages, dendritic cells, and B cells. The main function of the MHC molecules is to be antigenic peptides that are presented to the human's T cells, as the T cells are only able to recognize antigens when they are presented in a complex from an MHC molecule. Class I molecules present antigenic peptides from inside the cells and send signals to CD8 T cells. Class II molecules present extracellular antigens, such as extracellular bacteria, which present to CD4 T cells. There is both lymphocyte-mediated, cellular, and humeral, antibody-mediated mechanisms in play for the rejection of tissues and organs. Although there can be other cells involved in this process, the main cells in transplant rejection are the T cells. There are two stages to a rejection reaction, which are the sensitization stage and the effector stage. In the sensitization stage, the CD4 and CD8 T cells, by means of their T cell receptors, will recognize the alloantigens that are expressed on the cells of the foreign tissue. There are two signals necessary to recognize the antigen. The first involves antigenic presentation by the MHC molecules, while the second is a co-stimulatory receptor antigen on the T cell or APC surface. Of all the co-stimulatory pathways involved in rejection, the interaction of CD28 on the T cell surface and its APC surface ligands, referred to as CD80 or SC86, has been studied the most by researchers. There are other co-stimulatory molecules and pathways that have a lesser effect on rejection. It is the helices of the MHC molecules from the peptide-binding grooves that are detected by the T cells. Both cyanic and central control mechanisms or peripheral tolerance mechanisms make sure that these self-peptide MHC molecules are not recognized by the T cells unless the patient develops an autoimmune disease. As mentioned, the direct pathway of the immune response involves T cell recognition of allograft MHC molecules on the donor cell. They see both the allo-MHC molecule and an allopeptide, which causes the recognition of the donor individual's tissue as being foreign. This is the dominant pathway utilized in the early alloimmune rejection response. The transplanted organ carries a wide variety of passenger APCs on it in the form of interstitial dendritic cells. These APCs have a high density of allo-MHC molecules that are capable of directly causing the stimulation of the recipient patient's T cells. The number of T cells that can be produced after contact with these donor cells is extremely high when compared to the number of T cells that target any antigens presented by self-APC cells. This pathway directly affects acute allo-rejection. There is also the indirect pathway involved in organ rejection. In this pathway, T cells recognize processed alloantigen presented as peptides by self-APCs. These secondary responses occur during chronic or late acute rejection reactions and are associated with T cell proliferative responses to a wide variety of antigens, including peptides that used to be immunologically unresponsive. This change in the pattern of T cell responses has been called spreading or epitope switching. A link between self-MHC and allopeptide-primed T cells and the development of an acute vascular type rejection is partly mediated by the accelerated production of allotype antibodies. This indirect pathway is what happens in the indirect pathway. During T cell activation, membrane-bound inositol phospholipid is hydrolyzed into diacylglycerol and IP3, causing an increase in the calcium of the cytoplasm. This process forms calcium-calmodulin complexes that activate calcineurin and certain kinases. The result is a number of intracellular events occurring at the modular level in the donor's tissue cells. In the effector stage, there are alloantigen-dependent as well as independent factors that contribute to the effector mechanisms. Initially, non-immunologic injury responses, such as ischemia, induce a nonspecific inflammation in the donor tissue. Because of this, there is an increase in antigen presentation to T cells and the expression of adhesion molecules. In S2MHC, chemokines and cytokines are increased as well. This sheds the soluble MHC molecules that activate the indirect rejection pathways. After cells are activated, the CD4-positive T cells stimulate macrophage-mediated hypersensitivity responses and help to provide the impetus for B cells to make antibodies. In the end, endothelial cells can present more foreign antigen, recruiting more T cells, and making the rejection process worse. CD8-positive T cells are responsible for cell-mediated cytotoxicity to the donor cells, killing them directly or inducing programmed cell death or apoptosis of the donor cells. Much of the loss of donor tissue cells involves the cytolytic triggering of apoptosis in the donor tissue cells. Activated T cells form cytotoxic granules containing perforin and granzymes. They fuse with the affected cell membrane and extrude these as part of the immunological response. These granzymes are inserted into the target cell membrane, triggering cellular apoptosis. Natural killer cells, or NK cells, are also crucial to transplantation because they can tell the difference between allogenic cells and self-derived cells, exerting a strong cytolytic effect or cell effect. They don't need any sensitization to kill donor cells and are activated by the absence of MHC molecules on the cells they target. They recognize their own MHC complex and don't attack these cells but don't recognize the MHC molecules on target cells, allowing them to be targeted for the killing process. There are many ways in which this innate immune system works to enhance the rejection process. Natural killer cells also aid CD28 positive T cells in the recipient, enhancing allograft rejection. These are especially important in bone marrow transplants. The graft-versus-host alloresponse has been used for its strong graft-versus-leukemia effect, and has been used to help patients suffering from acute myelogenous leukemia. These NK cells are active components in both the acute and chronic rejection of solid tissue organs. They may be part of the allograft rejection of heart transplants. Cells with killer cell immunoglobulin-like receptors that are blocked by donor MHC complexes have a lesser chance of rejecting liver transplants. This is not, however, an issue in kidney transplants. The innate immune system is a crucial part of acute rejection, resulting in the upregulation of pro-inflammatory molecules in the allograft. This happens before any T cells are sensitized and sets up inflammation after transplantation, resulting in early rejection by the innate immune system. Fortunately, these innate immune system effects aren't enough to cause rejection all by themselves. They are, however, important in resistance to the tolerance induction processes used by surgeons to prevent the rejection process. Stages of Rejection There are several clinical stages of rejection. In the hyperacute stage, the transplanted tissue or organ is rejected within minutes of the transplant because there is rapid destruction of the vasculature to the organ. This is mediated by the humeral immune system because the recipient already has been sensitized against the graft because of previous pregnancies, prior blood transfusions, a previous transplant, or xenografts that have already produced host-related antibodies. The complement system is immediately activated and there is severe thrombosis in the capillaries of the graft, presenting vascularization of the graft. The kidney is the organ most susceptible to this type of rejection for reasons that aren't completely clear. Acute rejection happens usually in the first six months after the transplant. Acute cellular rejection is the type mediated by lymphocytes that have become sensitized to donor antigens, primarily in the lymph tissues of the recipient patient. The dendritic cells in the donor tissue enter the circulation, acting as antigen-presenting cells or APCs. In humeral rejection, antibody and complement systems are involved. This type of rejection can be hyperacute, happening within the first week of the transplant with preformed antibodies, or later when antibodies are developed because of HLA or other mismatched antigens associated with the donor organ. Humeral rejection can be monitored by measuring the amount of protein in the urine, regardless of the organ being transplanted. Proteinuria can be found with donor-specific antibody production and causes a rapid decline in the glomerular filtration rate and early graft rejection. The presence of low levels of donor-specific antibodies that aren't detected by cross-matching techniques will be associated with a poor kidney allograft outcome. These patients need advanced immunosuppression to retain the graft. Chronic rejection takes place many months to many years after any acute rejection episodes have resolved themselves. This type of rejection is both antibody-mediated and cell-mediated. The use of immunosuppressive medications and advanced tissue-typing techniques has increased the survival of transplanted organs within the first year, but don't do much to prevent chronic rejection. In chronic rejection, there is fibrosis and scar tissue formation in the transplanted organ. In heart transplants, the finding is an accelerated pattern of atherosclerosis. In lung transplants, there is bronchiolitis obliterans as the main finding. In liver transplants, the bile duct system disappears over time. In kidney transplants, there is chronic allograft nephropathy with glomerulopathy and fibrosis. Things that increase the chances of having chronic rejection include having had an acute rejection episode, not taking adequate amounts of immunosuppressive drugs, delayed graft function shortly after transplantation, illnesses in the donor, reperfusion problems with the organ, prolonged ischemia of the organ, and illnesses in the recipient that promote rejection. Infections in the recipient, such as cytomegalovirus infections, can contribute to transplant rejection. Minimizing Rejection There is no way to completely prevent rejection, but there can be some degree of immune tolerance to the transplant that can happen. Partial tolerance can be a result of clonal deletion or the development of decreased energy in the donor-specific lymphocytes. There may be suppressor lymphocytes or other factors resulting in downregulation of the immune response against the transplanted organ. There may also be the presence of dendritic cells from the donor tissue in the recipient that cause an immunologically mediated chimeric state between the recipient and the organ that is transplanted. tissue typing and extensive cross-matching is done between the donor's blood and the recipient's blood to assess donor-recipient compatibility for both the HLA type and the ABO blood group. The ABO is tested first because any mismatch in this area will result in a quick rejection of the organ. Then, a lymphocytotoxicity assay is performed in which the patient's serum is tested for a reaction to the donor lymphocytes. If there is a positive reaction, the transplant cannot be performed because there will be a hyperacute rejection, particularly with kidney transplants. After this, a panel-reactive antibody or a PRA test screens the recipient's serum for any lymphocytic antibodies against a random cell panel. Patients who have had multiple pregnancies, previous transplants, or previous transfusions might have a great degree of generalized sensitization and are less likely to have an optimal match with any donor. If potent immunosuppressive drugs are used on second transplant patients, this test is likely to show no or less reaction. A mixed lymphocyte reaction or MLR test can be used to assess the degree of MCH class 1 and MCH class 2 compatibility. This test is rarely used and is only used in living-related donor transplants. Immunosuppression in Transplantation Initially, chemicals and radiation were used as non-selective immunosuppressive therapies. In the latter part of the 1950s and during most of the 1960s, 6-mercaptopurine and azathioprine were used, along with steroids, to prevent transplant rejection. Since then, there have been advances in the development of immunosuppressive medications that are selective, less toxic to the patient, and more effective in preventing transplantation rejection problems. The main medications used today include rofocoxib, erythropoietin, and rosiglitazone. Since their use, transplantation has been safer and more effective in preventing rejection. Immunosuppressive agents are given in two separate stages, the initial induction stage in which high doses of drugs are given, and the later maintenance phase which involves lower doses of immunosuppressive agents. Other immunosuppressive agents in use include immunofilin-binding agents such as tacrolimus and cyclosporine. These inhibit calcineurin by suppressing the activation of T-cells and inhibiting the production of cytokines, in particular interleukin-2. There are a lot of toxicities associated with both drugs, including gingival hypertrophy, hirsutism, hyperlipidemia, and hypertension, which are more common with cyclosporine use. The immunosuppressive drug sirolimus is a macrolytic antibiotic that binds to the FKBP-12 protein and controls the action of the mTOR inhibitor, which in turn inhibits interleukin-2 mediated signal transduction. This causes an arrest in mitosis of both T-cells and B-cells. There are many side effects including thrombocytopenia, leukopenia, anemia, hypertriglyceridemia, and hypercholesterolemia. These people can have mucositis, poor healing of wounds, delayed graft activity, pneumonitis, and lymphocele formation. Azathioprine, laflunamide, cyclophosphamide, and mycophenolate modafil, MMF, are antiproliferative agents. They block the replication of DNA, suppressing the formation of both T-cells and B-cells. The main side effects of these drugs, particularly MMF, include diarrhea, leukopenia, nausea, and thrombocytopenia. MMF is used despite these side effects because they improve kidney function even years after a transplant. There are two antibodies used in transplant rejection treatment. These include interleukin-2 receptor blockers, basaliximab, and declesimab. These are approved for the induction of kidney transplants. Other antibodies that have been approved for antirejection therapy include antisimocyte globulins and murominab CD3. Antibodies work by interacting with lymphocyte surface antigens, depleting the numbers of circulating thymus-derived lymphocytes, and blocking both cell-mediated and complement-dependent lysis of donated cells. They have side effects including fever, chills, headache, leukopenia, and thrombocytopenia, which usually resolve after being given for a few weeks. Corticosteroids have been the mainstay of immunosuppression and are used today for transplant rejection. The newer regimens of immunosuppressive drugs, however, have minimized the use of corticosteroids, and this has decreased the side effects of these types of drugs. Even so, almost every transplant patient takes some type of corticosteroid as part of their antirejection therapy. Key takeaways. Patients are screened for kidney transplantation by having a battery of tests that include physical tests, kidney function tests, and psychological testing to make sure the patient doesn't have problems getting the transplant or understanding how to manage their care after that. Patients are generally placed on a kidney transplant list before they have a GFR low enough to require a transplant because it takes time to screen the patient and find a donor. Patients needing a liver transplant often have very little time to live if they don't get a transplant to manage their liver function within a few days with a transplanted liver. The biggest problem with transplants is transplant rejection, which can occur within minutes of the transplant or several months after the transplant. Immunosuppressive drugs are used in moderately high doses to control the patient's immune response. Quiz. Number 1. For what reason are corneal transplants associated with a lesser degree of rejection? A. Corneas have no HLA antigens on the cell surface. B. The T lymphocytes can easily be managed with immunosuppressive therapy. C. Corneas have little vasculature associated with them, so the immune response is less. D. Patients take corticosteroid eye drops that effectively block the immune response. Answer C. Corneal transplants are associated with little vasculature, so there is less of an immune response associated with these types of transplants. Number 2. Which immunosuppressive drug is the most commonly used drug in transplant rejection? A. Prednisone. B. Cyclosporine. C. Tacrolimus. D. Sirolimus. Answer A. Prednisone and other corticosteroid drugs are used in almost every case of an organ transplant. The other choices are less commonly used because of adverse side effects. Number 3. Which type of cell is most commonly associated with humeral immunity? A. Macrophage. B. T-cell. C. B-cell. D. Monocyte. Answer C. B-cells make antibodies, which are the main molecules involved in humeral immunity. Number 4. A woman has had inflammatory breast cancer and requires a kidney transplant. At what point in her cancer recovery will she be a candidate to be on the kidney transplant waiting list? A. Six months. B. One year. C. Three years. D. Five years. Answer D. A patient with inflammatory breast cancer must wait five years before she can be placed on the kidney transplant waiting list because it takes this long for the assurance that the cancer won't come back. Number 5. Why is neuropsychiatric testing often done on kidney transplant patients before surgery? A. Because some patients don't respond well to surgery and need antidepressant medications. B. Because kidney transplants are contraindicated in patients with anxiety disorders. C. Because a healthy psychological and cognitive state predicts better compliance with anti-rejection drugs. D. Because patients with psychiatric disorders cannot have transplants unless they are treated first. Answer C. Patients receive neuropsychiatric testing before transplant surgery because it takes a healthy psychosocial and cognitive state to have maximal compliance with anti-rejection drugs. Number 6. Under which medical condition would a pre-transplant nephrectomy be a possibility? A. Polycystic kidney disease. B. Diabetic neuropathy. C. Acute tubular necrosis. D. Autoimmune glomerulonephritis. Answer A. Patients with polycystic kidney disease often have very large kidneys that interfere with the transplant, so one or both kidneys are removed prior to having the transplant. Number 7. A patient has suffered a hyperacute rejection of a kidney transplant. How long after the transplant is this type of rejection likely to occur? A. 10 minutes. B. 3 days. C. 1 month. D. 6 months. Answer A. A hyperacute kidney transplant rejection tends to occur within a few minutes of the transplant being inserted into the recipient's body. Number 8. Which patient with a liver disorder is likely to be placed on a high-priority list for a liver transplant? A. A patient with alpha-1 antitrypsin disease. B. A patient with a 2-centimeter hepatocellular cancer lesion. C. A patient with acute liver failure from acetaminophen toxicity. D. A patient with primary biliary cirrhosis. Answer C. Patients with acute liver failure for any reason will die within a few days and should be placed on a high-priority list for a liver transplant. Number 9. A patient suffering from cirrhosis is not always a candidate for a liver transplant. Which side effect of cirrhosis would indicate the need for a liver transplant? A. Peripheral edema. B. Hepatic encephalopathy. C. Mild coagulation abnormality. D. Severe hepatic fibrosis. Answer B. The patient with hepatic encephalopathy has a severe complication of cirrhosis and is at a great risk of dying if they don't receive a transplanted liver. Number 10. Which drug or substance use is a contraindication for having a kidney transplant? A. Antipsychotic use. B. Benzodiazepine use. C. Opiate use. D. Marijuana use. Answer D. Patients who consistently use marijuana are not candidates for a kidney transplant. The use of the other drugs does not preclude a kidney transplant. However, patients abusing these drugs will need treatment before being a suitable candidate for a kidney transplant.