You are in: eMedicine Specialties > Emergency Medicine > GENITOURINARY Transplants, RenalArticle Last Updated: Jul 12, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 10
 
Author: Richard Sinert, DO, Associate Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center Richard Sinert is a member of the following medical societies: American College of Physicians and Society for Academic Emergency Medicine Coauthor(s): Mert Erogul, MD, Assistant Professor of Emergency Medicine, University Hospital of Brooklyn: Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center Editors: James Li, MD, Assistant Professor, Division of Emergency Medicine, Harvard Medical School; Board of Directors, Remote Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Richard Sinert, DO, Associate Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center; John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center; Jonathan Adler, MD, Attending Physician, Department of Emergency Medicine, Massachusetts General Hospital; Division of Emergency Medicine, Harvard Medical School Author and Editor Disclosure Synonyms and related keywords: renal transplantation, kidney transplant, kidney transplantation, organ transplant, organ transplantation, end-stage renal disease, ESRD, kidney disease, kidney failure, renal failure, renal transplant BACKGROUNDSection 2 of 10
 
Emergency department (ED) physicians encounter transplant patients at two critical stages. First, they may be the initial physicians to identify potential donors from the pool of critically ill patients admitted to the hospital. And second, they care for patients once they have been transplanted, a population that continues to expand as the procedure becomes more common and the patients longer lived. Despite increases in the number of transplants, organ availability is still a problem. At this writing, 92,237 patients are waiting for transplant in the United States. Once the organ is transplanted, patients commonly present to the ED with complications uniquely related to their immunosuppressive regimens. Often, these patients present with unusual and potentially life-threatening infections. In addition, acute renal failure in such patients is common. This article reviews the role of the ED physician in organ procurement and discusses common medical complications observed in patients who have undergone renal transplantations. For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center. Also, see eMedicine's patient education article Kidney Transplant. For further information, see Mayo Clinic - Kidney Transplant Information. ORGAN PROCUREMENTSection 3 of 10
ED physicians should be familiar with individual departmental policies on brain death and organ procurement. Telephone numbers for local transplant coordinators should be displayed prominently. Brain death determination The Uniform Determination of Death Act provides guidelines outlining neurologic criteria for brain death, which is defined as complete and irreversible loss of brain and brainstem function. Criteria include cerebral unresponsiveness, brainstem areflexia, and apnea in the absence of hypothermia and drug intoxication. Because of the lengthy process required for actual organ procurement, the ED physician should not wait for the formal declaration of brain death before involving the transplant team. Transplant coordinators should be called early for any patient who may meet brain death criteria in the near future. The wet ischemia time—that is, the time from cessation of circulation to removal of the organ and its placement in cold storage—should be no longer than 30 minutes. This reality and other practical and logistical factors prevent "code victims" in the ED from becoming solid organ donors. However, keep in mind that patients who die in the ED should be considered for donation of other tissues such as bone, skin, veins, heart valves, and ocular components. Donor selection Increasing demand for donor organs and improvements in transplant immunology have greatly expanded the pool of patients eligible to donate organs. Absolute contraindications for organ donation include HIV, sepsis, and non-CNS malignancy. Advanced age is a relative contraindication; most Organ Procurement Organizations (OPOs) do not harvest solid organs from individuals older than 75 years. However, ED physicians should to defer rejection of questionable transplant donations to an OPO representative. Donation procedure The task of discussing organ donation with a patient's family is best left to the transplant coordinator, who is highly trained for such discussion and is not involved in the acute care of the patient. The ED physician should focus on identifying possible donor candidates and on providing the family with a realistic prognosis for the patient. The pretransplantation workup of a potential donor should include screening for transmissible infectious agents such as herpesvirus (CMV, HSV, EBV); HIV; hepatitis viruses A, B, C, D and E; and the human T-cell lymphotropic virus type 1. Donor management Following brain death, a number of physiological changes occur that require intervention if donor organ perfusion is to be preserved. Increasing cerebral edema after a trauma or stroke initially results in elevated catecholamine release and hypertension. With brainstem necrosis, catecholamine levels drop rapidly to a fraction of normal values, causing hypotension. Such hypotension should be corrected with fluids and vasopressors. Approximately three fourths of organ donors develop diabetes insipidus due to pituitary necrosis. If this condition is untreated, significant hypovolemia may result. Systemic thermal control is often lost because of hypothalamic ischemia. This occurs in most donors and results in detrimental effects on potential donor organs, including coagulopathy, hypoxia, hepatic dysfunction, and cardiac dysfunction. Potential donors with brain death and preserved cardiovascular function who are identified in the ED should be quickly admitted to an intensive care unit. Only in this setting can their cardiorespiratory status be maintained against the onslaught of physiologic insults that ensue once neurologic function has ceased. Once stabilized, the organ donor may officially be designated brain dead and transferred to the operating room for organ harvesting. POSTTRANSPLANTATION MORBIDITY AND MORTALITYSection 4 of 10
Graft prognosis Graft prognosis is directly related to the source of the donor kidney: recipients of cadaveric kidneys generally have more episodes of rejection and lower graft survival rates. The graft survival rate for kidneys from living donors is approximately 95% at 1 year and 76% at 5 years, whereas the graft survival rate for kidneys from cadaveric donors is 89% at 1 year and 61% at 5 years. Morbidity In addition to complications of transplantation such as infection and graft failure, the major causes of morbidity after renal transplantation are hypertension (occurring 75-85% of all renal transplant recipients), hyperlipidemia (60%), cardiovascular disease (15.8-23%—a 10-fold increase over the general population), diabetes mellitus (16.9-19.9%), osteoporosis (60%), malignant neoplasm (14%). Cardiovascular disease is increased 10-fold compared with the general population, and the rate of malignancies appears to be related to the degree of immunosuppression. Diabetes is more likely to be present prior to transplantation, and new-onset diabetes is related to corticosteroid use after transplantation. Mortality Predictably, recipients from living related donors have lower mortality rates than recipients from cadaveric donors. This is likely related to fewer rejection episodes and thus lower immunosuppression requirements. The survival rate of patients after transplantation from a living donor is 98% at 1 year and 91% at 5 years; the survival rate after cadaveric donation is 95% at 1 year and 81% at 5 years. Common causes include coronary artery disease (30.4%), sepsis (27.1%), neoplasm (13%), and stroke (8%). During the first year posttransplantation, most deaths are due to infectious causes. Long-term mortality rates are more closely related to the development of coronary artery disease. IMPORTANT HISTORY IN TRANSPLANTATION COMPLICATIONSSection 5 of 10
When taking a history from a patient with an organ transplant, many elements vary from the routine patient. The following are of particular importance in the history of any patient with an organ transplant presenting to the ED:
In patients with renal transplants, many of the specific etiologies of infections can be correlated to the age of the graft. Most opportunistic infections occur after the first month post transplant up through the first year, but especially between months 1 and 6 when immunosuppression is maximized. As previously noted, patients with cadaveric grafts have significantly lower graft survival rates and increased infectious complications. Patients with multiple rejection episodes requiring more aggressive immunosuppression are at significantly higher risk for infectious complications than patients who have experienced little or no rejection. Noncompliance with antirejection medications is the leading cause of late acute rejection. A complete medication history must include all over-the-counter medications. Cyclosporine is especially important to note because of its wide range of drug interactions. Also important to note are recent exposures to patients with infections (eg, chickenpox, cytomegalovirus [CMV], tuberculosis) and history of chronic infections (eg, CMV, Epstein-Barr virus [EBV], hepatitis). Reactivation of chronic infections and exposures is the most common source of infections in transplant patients. Other information necessary in evaluation of any illness is blood pressure, body weight, serum creatinine, and cyclosporine levels. Patients with renal transplants or their families usually are very knowledgeable about their baseline status and are valuable sources of important clinical data. EXAMINATION POINTS IN A TRANSPLANT RECIPIENTSection 6 of 10
Fever is the most common presentation of an infection in patients with transplants. Be aware that uremia, hyperglycemia, and immunosuppressants (including steroids) commonly suppress or mask fever. In patients with renal transplants, assessment of volume status is paramount. Hypotension and tachycardia are obvious clues to hypovolemia. Edema is a less reliable finding owing to chronic hypoalbuminemia from malnutrition, nephrotic syndrome, and chronic liver disease common in these patients. Often, invasive hemodynamic monitoring is the only reliable means of determining volume status in patients with renal transplants. The renal graft generally is placed in the right iliac fossa in an extraperitoneal position and is most often anastomosed to the internal or external iliac artery. It should be inspected, palpated, and auscultated. The graft insertion site should be inspected for signs of wound infection. Graft tenderness and swelling often are observed in acute rejection, outflow obstruction, pyelonephritis, and renal vein occlusion. Bruits often can be heard in cases of renal artery stenosis and arteriovenous malformation. COMPLICATIONS ASSOCIATED WITH RENAL TRANSPLANTATIONSSection 7 of 10
Anatomic complications Renal artery thrombosis: Renal artery thrombosis is generally appreciated during the immediate posttransplant hospitalization, but it may present later. It is caused by a low flow state from hypotension or vascular kinking due to surgical error. The presenting symptom is sudden cessation of urine output, and the likely outcome is graft loss. This is diagnosed by color flow Doppler. Renal artery stenosis: Renal artery stenosis is usually a late complication. It presents as uncontrolled hypertension, allograft dysfunction, and peripheral edema. It is diagnosed by color Doppler ultrasonography or MRA. Renal vein thrombosis: Renal vein thrombosis is typically an early complication presenting as graft tenderness and edema. The patient develops dark hematuria and diminished urine volume. It is diagnosed by color flow Doppler. Urine leak: Urine leak results from disruption of the anastomotic connection of the ureter to the graft; this generally within the first 2 months post transplant. Symptoms include fever, pain, abdominal swelling, and graft dysfunction. Ultrasonography demonstrates perigraft fluid collection. Ureter obstruction: Late posttransplant obstruction can be due to hematuria or chronic fibrotic changes at the anastomosis site. The graft becomes distended and edematous, and ultrasonography reveals hydronephrosis. Infection Infection is the most common cause of first-year posttransplantation mortality and morbidity. During the first posttransplantation year, 40-80 percent of transplant recipients experience at least 1 infection; however, these numbers are decreasing as more transplant recipients receive preoperative immunizations and take posttransplantation antibiotic prophylaxis. Infection most commonly occurs in mucocutaneous areas (41.0%), the urinary tract (17.2%), and the respiratory tract (13.9%). The most common infective agents were bacterial (45.9%), viral (40.6%), fungal (12.5%), and protozoan (1%). CMV (31.5%), herpes simplex (23.4%), and herpes zoster (23.4%) were the most frequent viral illnesses. Infection (32%) was the most common cause of death; pneumonias accounted for 50% of the patient deaths from infection. Infectious agents can often be identified by the time interval from transplantation to presentation. The first posttransplantation month is dominated by infections directly related to the surgery. These entities include urinary tract infections (Escherichia coli), line infections (Staphylococcus aureus, Streptococcus viridans), wound infections (S aureus, S viridans), and pneumonia (Streptococcus pneumoniae). The initial 6 posttransplant months are associated with the highest levels of immunosuppression and, thus, carry the greatest risk of viral and opportunistic infections. CMV is responsible for more than two thirds of febrile episodes during this period. These patients often present with fever, malaise, lymphadenopathy, arthralgias, and myalgias. Laboratory studies show leukopenia with atypical lymphocytes and mild hypertransaminasemia. Diagnosis is based upon isolation of virus or antibody titers. Untreated CMV has been associated with a mortality rate as high as 15%. Other opportunistic infections include Pneumocystis carinii pneumonia, listeriosis meningitis, and sepsis with the organism Aspergillus fumigatus. After the first 6 months, patients with renal transplants are divided into the following 3 subgroups:
Malignancy Transplant recipients are at significantly higher risk for cancers than the general population because of (1) chronic immunosuppression, (2) chronic antigenic stimulation, (3) increased susceptibility to oncogenic viral infections, and (4) direct neoplastic action of immunosuppressants. Transplant recipients have a significant overall 2-5 fold higher risk in both sexes for cancers of the colon, larynx, lung, and bladder and in men for cancers of the prostate and testis. Especially high risks, 10-30 fold, exist for cancers of the lip, skin (nonmelanoma), kidney endocrine glands, non-Hodgkin lymphoma, and, in women, cervix and vulva-vagina. Liver disease Chronic liver disease is an important cause of morbidity and mortality for patients with renal transplants. Etiologies of hepatic dysfunction include viral hepatitis and antirejection therapy. Of the viral infections, CMV is the leading cause of hepatic dysfunction, followed by hepatitis C and B. Of antirejection medications, azathioprine and cyclosporine are known to cause cholestatic jaundice. Acute renal failure Failure of renal allografts is now one of the most common causes of ESRD, accounting for 25% of all patients awaiting renal transplants. Renal transplants can fail for all the same causes as native kidneys. In addition, renal grafts can fail for causes unique to transplant patients. Complications of surgery are common causes of graft failure within the first 12 weeks after transplantation. Such complications include renal artery stenosis or thrombosis, urinary tract obstruction, and renal vein thrombosis. Recurrent renal disease results in fewer than 4% of graft failures but may be an important concomitant etiology of renal failure. Rejection is related primarily to activation of T cells, which, in turn, stimulate specific antibodies against the graft. Various clinical syndromes of rejection can be correlated with the length of time after transplantation. Hyperacute rejection occurs immediately in the operating room, when the graft becomes mottled and cyanotic. This type of rejection is due to unrecognized compatibility of blood groups A, AB, B, and O (ABO) or a positive T-cell crossmatch. Acute rejection appears within the first 3 posttransplant months and affects 30% of cadaveric transplants and 27% of transplants from living donors. Approximately 20% of patients with transplants experience recurrent rejection episodes. Patients present with decreasing urine output, hypertension, rising creatinine, and mild leukocytosis. Fever, graft swelling, pain, and tenderness may be observed with severe rejection episodes. Rejection is secondary to prior sensitization to donor alloantigens (occult T-cell crossmatch) or a positive B-cell crossmatch. The final diagnosis depends upon a graft biopsy. Late acute rejection is correlated highly with withdrawal of immunosuppressive therapy 6 months after transplantation. Chronic rejection occurs more than 1 year after transplantation and is due to immunologic agents and cellular and humoral factors. These patients present with a progressive loss of renal function over time. Cyclosporine toxicity Cyclosporine and tacrolimus (FK-506) nephrotoxicity is related to hemodynamic factors. Acute cyclosporine toxicity (serum level >300 ng/mL) causes vasoconstriction and renal ischemia, which can be reversed by decreasing drug dosage. Chronic toxicity results in fixed vascular lesions and irreversible renal ischemia. Cyclosporine is noteworthy for its many interactions with other medications. Calcium channel antagonists (eg, diltiazem, verapamil, nicardipine) and certain antibiotics (eg, erythromycin, doxycycline, ketoconazole) increase levels of cyclosporine. Certain antibiotics (eg, nafcillin, cotrimoxazole, isoniazid, rifampin) and certain anticonvulsants (eg, phenytoin, phenobarbital, carbamazepine) decrease levels of cyclosporine. Drugs that enhance the nephrotoxicity of cyclosporine without altering blood levels include amphotericin B, acyclovir, and nonsteroidal anti-inflammatory drugs. Hypertension Approximately 50% of all renal transplant patients have hypertension. Possible etiologies of hypertension include graft rejection, cyclosporine toxicity, glomerulonephritis, graft renal artery stenosis, essential hypertension from native kidneys, hypercalcemia, and steroid use. Cardiovascular complications Overall, risk of cardiovascular disease after transplant is 3-5 times that for age- and sex-matched controls. Risk factors for such disease include pretransplant cardiac disease, hyperlipidemia secondary to antirejection medications, hypertension, steroid use, type 1 diabetes mellitus, erythrocytosis, smoking history, and multiple previous rejection episodes. MANAGEMENT STRATEGIES FOR COMMON PRESENTATIONSSection 8 of 10
Workup of suspected infection Obtain the following studies:
Urinary tract infections from indwelling catheters are the most common source of bacterial infections in this patient population, and account for up to 69% of bacterial infections. Leukocytosis with a left shift commonly is observed with bacterial infections unless immunosuppressive agents have suppressed the bone marrow. Leukopenia with an increase in atypical lymphocytes commonly is observed with viral infections. Patients may present with pneumonia from bacterial or viral agents. Interstitial infiltrates commonly are observed with P carinii and other atypical pneumonias. Tuberculosis may present with typical upper lobe distribution in reactivation forms; however, tuberculosis also may present atypically as a primary infection. Ultrasonography is performed to identify urinary obstruction as well as fluid collections suggesting urine extravasation, abscess, pyelonephritis, or wound infection. Workup of acute renal failure Renal failure in patients with transplants is defined as a 20% rise in serum creatinine (as opposed to a 50% rise in nontransplant patients). In the workup, estimate the patient's volume status. Hypovolemia should be corrected rapidly in all patients. Order the following studies:
Urinalysis showing red cells raises suspicion for glomerulonephritis. White cells raise suspicion for infection and obstruction. Hyperkalemia is a common complication of renal graft rejection and cyclosporine use. Cyclosporine levels greater than 300 ng/mL are associated with increased nephrotoxicity. Transplant ultrasonography is performed to identify urinary obstruction. Color flow Doppler ultrasonography is necessary to evaluate vascular occlusion or stenosis. Renal biopsy represents the ultimate diagnostic modality and usually is required to diagnose most renal graft dysfunction definitively. OTHER CONSIDERATIONSSection 9 of 10
Blood transfusion Because of the risk of transmitting infection by transfusion, immunosuppressed transplant recipients should receive CMV-negative irradiated blood. Stress-dose corticosteroid coverage Severely ill transplanted patients on long-term steroid therapy are at risk of adrenal insufficiency and should be treated with stress doses of hydrocortisone (100 mg IV q8h). Conclusions Transplant recipients are among the most experienced patients that are seen in the emergency department. Many of them have dealt with their chronic illness for years, have been treated and examined by innumerable doctors, have undergone dialysis and its attendant intrusions on their lifestyle, have managed a complicated regimen of medications, and often have developed a certain expertise related to their own care. They are invariably grateful for any recognition or acknowledgment of their ordeal, and given their expertise, they should be educated about and encouraged to be active participants in their disease management to whatever extent possible. That said, their problems are frequently very complex and decisions regarding their care should be made in conjunction with the appropriate transplant team. REFERENCESSection 10 of 10
Article Last Updated: Jul 12, 2006 |
