Renal transplantation is the preferred treatment for end-stage renal disease. Vascular complications that occur following renal transplantation include renal artery stenosis, allograft infarction, arteriovenous fistulas, pseudoaneurysm, and renal vein thrombosis. Nonvascular complications include ureteral obstruction, urine leak, periallograft fluid collections (hematomas, lymphoceles, and abscesses), neoplasms, GI complications, and posttransplant lymphoproliferative disease.26 The major causes of renal transplant loss are death from vascular, malignant, or infectious disease, and loss of the allograft from chronic renal dysfunction associated with the development of graft fibrosis and glomerulosclerosis. Medication changes, as well as imaging contrast agent use that may affect renal function (including gadolinium-based contrast agents), should be discussed with the patient's transplant team.
Table 297-6 lists recommendations on diagnostic testing in transplant patients, including renal transplant patients. The serum creatinine level is the most valuable prognostic marker of graft function at all times after transplantation and should be obtained whenever renal failure or infection is suspected. The urinalysis provides important clues to acute changes in graft viability. Red blood cell casts and proteinuria are commonly seen in recurrent or de novo glomerulonephritis. The presence of WBCs, bacteria, and nitrites is helpful in diagnosing urinary tract infections. Proteinuria may signal rejection, drug toxicity, glomerular disease, or other graft nephropathy, although proteinuria from a remaining native kidney should also be considered. Obtain cyclosporine or tacrolimus blood levels for all patients on these medications. Contact the patient's transplant team regarding abnormal drug levels, because low drug levels are sometimes deliberately used to reduce side effects.
Ultrasonography is the best test to detect urinary obstruction. Renal graft ultrasonography can also be useful in patients suspected of having pyelonephritis, vascular abnormalities (stenosis, thrombosis, pseudoaneurysm, and arteriovenous fistula), perinephric abscess, urine leak, wound infection, or an episode of rejection.
MRI can be helpful in evaluating hematomas and other fluid collections, vascular abnormalities, and small infarcts caused by medication-induced vasculitis. Magnetic resonance angiography has the advantage of requiring either no contrast material or a gadolinium chelate that is less nephrotoxic than other agents. However, gadolinium-based contrast agents can cause acute renal failure in up to 3.5% of patients with underlying chronic renal insufficiency.27 Therefore, the patient's transplant team should be consulted before using gadolinium-based contrast agents.
GRAFT DYSFUNCTION AND FAILURE
Chronic renal dysfunction precedes the majority of graft failures. Acute renal failure in transplant patients is defined as a 20% rise from baseline serum creatinine levels, as opposed to a 50% rise in other patients with acute renal failure. Consider the conditions described in Table 297-9 when evaluating possible graft dysfunction or even a small increase in serum creatinine.28,29
TABLE 297-9Differential Diagnosis of Renal Allograft Dysfunction ||Download (.pdf) TABLE 297-9 Differential Diagnosis of Renal Allograft Dysfunction
|Deferential Disorder ||Comments |
|Mechanical ||At ultrasonography, a urine leak (i.e., urinoma) appears as a well-defined, anechoic fluid collection with no septations that increases in size rapidly. |
| Complications of surgery |
| Ureteral obstruction |
| Urine leak: urinoma, ascites, or abscess |
|Vascular ||The transplanted kidney is usually placed extraperitoneally in the right iliac fossa. End-to-side anastomosis to the external iliac vasculature provides circulation. Color duplex imaging of the renal artery and vein is helpful in assessing renal vascular stenosis or thrombosis. |
| Renal artery stenosis or thrombosis (12%) |
| Renal vein thrombosis |
| Renal artery and renal vein thrombosis are uncommon; they usually occur in the first month after transplant. |
|Glomerulonephritis || |
| Infection ||Urinary tract infections are the most common source of bacteremia in renal transplant recipients, and infectious diseases are the second leading cause of death in this population. See "Posttransplant Infections" section. |
| Urinary tract infection |
| Interstitial nephritis from polyoma BK virus, cytomegalovirus, herpes viruses 1 and 2, and adenovirus |
|Rejection ||Most common presentation of rejection in renal transplant patients is hypertension and falling urine output. Comparison of creatinine at the time of presentation to prior levels is critical. Fever may be a presentation for rejection. |
| Hyperacute |
| Acute |
| Late (recurrent acute) |
| Chronic cellular |
| Chronic humoral |
|Recurrent pyelonephritis/vesicoureteral reflux ||— |
|Nephrotoxic agents ||Drug serum levels do not correlate well with the degree of renal damage. Nonsteroidal anti-inflammatory drugs are contraindicated in this group. Avoid contrast agents if possible. |
| Aminoglycosides, fluoroquinolones, cidofovir, foscarnet, sulfonamides, calcineurin inhibitors (cyclosporin A and tacrolimus), nonsteroidal anti-inflammatory drugs, gadolinium-based and some other contrast agents, herbal preparations |
|Noncompliance with ||Diabetes often follows transplantation; marked exacerbations in hypertension are frequently associated with graft failure. |
| Medications |
| Management of risk factors such as diabetes and hypertension |
|Chronic allograft nephropathy ||— |
The most common reasons for ED visits are fever and abdominal pain.6 Complications include bleeding, rejection, and infection, as well as biliary, vascular, and wound complications. Bacterial infection may accompany acute rejection.30 Specific complications of liver transplantation are listed in Table 297-10. Obtain a CBC with platelet count and differential; serum chemistries, including electrolytes, BUN, creatinine, basic coagulation studies, liver function tests, amylase, and lipase levels; and cultures of blood, urine, bile, and ascites. Radiographic testing as indicated may include chest x-ray and abdominal ultrasonography with Doppler flow studies. US with Doppler can identify fluid collections, thrombosis of the hepatic artery or portal vein, and dilatation of the biliary tree (although the absence of biliary dilatation does not exclude obstruction or other posttransplantation pathology). With partial obstruction, the intrahepatic ductal system often does not appear to be dilated appreciably by US. With complete obstruction, duct dilation is usually seen. Patients often require cholangiography for complete evaluation. Patients with choledochocholedochostomy may be best evaluated by endoscopic retrograde cholangiopancreatography because it permits both a radiographic diagnosis and the potential for nonoperative intervention. Patients with a Roux-en-Y hepaticojejunostomy or those who cannot have endoscopic retrograde cholangiopancreatography must undergo percutaneous cholangiography. Early, broad-spectrum prophylactic antibiotics should be administered before any biliary tract manipulation. Discuss treatment and disposition with the transplant team.
TABLE 297-10Complications of Liver Transplantation ||Download (.pdf) TABLE 297-10 Complications of Liver Transplantation
|Complication ||Comments |
|Bleeding complications ||GI bleeding should be managed in the usual fashion but may signal graft dysfunction. |
|Biliary complications ||Bile leaks present early and biliary strictures present late (>2 mo from transplant). In both cases, cholestatic liver enzymes are elevated, typically with right upper quadrant pain (more pronounced with bile leak). |
| Bile leak || |
| Biliary stricture || |
|Hepatic artery complications ||CT with contrast (if renal function adequate) or US is helpful in the evaluation of these conditions. |
| Hepatic artery thrombosis || |
| Hepatic vein thrombosis || |
| Portal vein complications || |
|Rejection ||Early alkaline phosphatase and bilirubin levels rise, followed by a rise in aspartate aminotransferase and alanine aminotransferase. |
|Neurologic complications ||Causes include hemorrhage, cerebrovascular infarct, cerebral abscess, hypertensive encephalopathy, osmotic demyelination syndrome, and sinus thrombosis. MRI is best for evaluation. |
|Malignancy ||Increased risk for squamous cell carcinoma, lymphomas, and posttransplant lymphoproliferative disorder. |
Fever, cough, and increasing dyspnea are common reasons for ED visits in lung transplant patients. Important clinical features to note are the respiratory rate, pulse oximetry measurement, and physical findings of cyanosis, diaphoresis, use of accessory muscles, signs of congestive heart failure, and adequacy of peripheral perfusion. Obtain a chest radiograph and arterial blood gas analysis when adequacy of ventilation is in question. Give β2-agonists and anticholinergics as indicated. Signs of infection often overlap with the signs and symptoms of rejection, and the management of infection is quite different from that of rejection. A drop in the forced expiratory volume in 1 second of >10% warrants clinical investigation, but pulmonary function testing cannot distinguish between acute rejection, infection, and nonimmunologic causes of respiratory dysfunction such as airway stenosis.31 Therefore, bronchoscopy is required for specific diagnosis. Lung transplant patients can deteriorate very quickly in the absence of the proper therapy. Thus, it is common practice to cover both infection and rejection until additional histopathologic and culture results are obtained.32
COMPLICATIONS OF LUNG TRANSPLANTATION
Complications occur most frequently in the first year but can occur at any time starting from the first few weeks after transplant and continue throughout the lifetime of the patient (Table 297-11).32,33 Indications for hospital admission are listed in Table 297-12.
TABLE 297-11Time Course of Lung Transplant Complications ||Download (.pdf) TABLE 297-11 Time Course of Lung Transplant Complications
|Days after Transplant ||Complications Most Commonly Seen in Each Time Period |
|0–3 d || |
Hemorrhage from technical/mechanical problems
|3 d–1 mo || |
Infection: bacterial, mycoplasma, community respiratory viruses
|Starting at 1 mo || |
Bacterial, fungal, community respiratory viral (can occur at any later time)
Mycoplasma 0–4 mo
Mycobacteria after 4 mo
|Other ||Cytomegalovirus infection and Pneumocystis jiroveci pneumonia may occur any time, but are more common when prophylaxis is not being given, especially when such treatment has been recently discontinued. |
TABLE 297-12Indications for Hospital Admission for Lung Transplant Patients ||Download (.pdf) TABLE 297-12 Indications for Hospital Admission for Lung Transplant Patients
Decompensated congestive heart failure or pulmonary edema
Rapidly progressive airflow limitation (forced expiratory volume in 1 second decreases >10% over 48 h)
Acute rejection is common and may occur three to six times in the first postoperative year. After the first year, the frequency of acute rejection decreases, but it can occur for several years after transplant. Signs of rejection include cough, chest tightness, increase or decrease in temperature from baseline of >0.28°C (0.5°F), hypoxemia, decline in forced expiratory volume in 1 second (10% or more), and infiltrates on the chest radiograph. Radiographic abnormalities are less common >6 weeks after transplant, and an acute rejection episode actually may be "radiographically silent" after this. Discuss treatment with the transplant team. If the maintenance immunosuppressant regimen has been tapered, it can be very helpful to return to pretaper dosages. In addition, high-dose corticosteroids are often used to treat acute rejection. The usual dosing regimen is 15 milligrams/kg of IV methylprednisolone each day for 3 consecutive days. After the corticosteroid bolus, if the maintenance prednisone had been tapered, increasing the prednisone to 1 milligram/kg/d and tapering over the next 10 days may be helpful.31 Clinical response to treatment is gauged by improvements in oxygenation, spirometry, and radiographic appearance and typically occurs within 24 to 48 hours after treatment is initiated. Failure to improve should suggest infection as an alternative diagnosis. After clinical improvement, the maintenance dose of prednisone is increased, with a slow taper back to baseline.
Pulmonary infections from bacteria, fungi, or viruses are the most common causes of morbidity and mortality in lung transplant patients34,35 (Tables 297-5 and 297-11). Lung transplant patients are at risk for pneumonia because of colonization of the recipient's airway in the setting of transplantation for bronchiectasis and cystic fibrosis and at risk of aspiration in the presence of gastroesophageal reflux disease.33 Antibiotic selection is best left to the lung transplant specialist.
Cardiac transplantation has been applied successfully to patients of all ages, from newborns through persons in their late 60s. Heart transplantation is indicated for patients with end-stage heart failure not remediable by standard medical or surgical therapy. Many in the latter group will have undergone previous coronary artery bypass or valve surgery or been bridged on mechanical assist devices. The leading causes of death in those age 60 to 69 are graft failure and infection.36
The success of a heart transplantation operation depends on the ability of the denervated heart to support the normal circulation. The lack of sympathetic and parasympathetic innervation does, however, induce an altered physiologic state. The denervated heart has a normal sinus rhythm with a heart rate between 90 and 100 beats/min. Denervation results in the absence of the initial centrally mediated tachycardia in response to stress or exercise, but the heart remains responsive to circulating catecholamines. Thus, the cardiac response to stress or exertion is blunted. With proper conditioning, patients are able to resume normal activity levels, including vigorous exercise, following transplantation.
The donor heart is implanted with its own sinus node intact to preserve normal atrioventricular conduction. The technique of cardiac transplantation also results in preservation of the recipient's sinus node at the superior cavoatrial junction, and the two sinus nodes remain electrically isolated from each other. Thus, ECGs frequently will have two distinct P waves (Figure 297-2). The sinus node of the donor heart is easily identified by its constant 1:1 relationship to the QRS complex, whereas the native P wave marches through the donor heart rhythm independently. The presence of the two separate P waves may lead to confusion about the patient's rhythm, mistakenly interpreting sinus rhythm as second-degree heart block. The ECGs may also be interpreted erroneously as showing atrial fibrillation, atrial flutter, or frequent premature atrial complexes. Some patients may have evidence of "cardiomegaly" related to the transplantation of a heart from a donor who was larger than the recipient (Figure 297-3). Clinical evaluation is based on the reason for the ED visit. Chest x-ray, ECG, and further evaluation are based on complications of cardiac transplantation (Table 297-13) and underlying patient comorbidities, especially in elderly transplant recipients.
TABLE 297-13Complications after Cardiac Transplant ||Download (.pdf) TABLE 297-13 Complications after Cardiac Transplant
|Complication ||Comments |
|Altered physiology ||See text in Cardiac Transplantation section. |
|Dysrhythmias ||Dysrhythmias after transplantation are frequently due to rejection. Treat the unstable patient presenting in extremis with 1 gram of methylprednisolone IV; delay rejection therapy in the stable patient for consult with the transplant team and biopsy. Atropine has no effect due to denervation. |
|Sinus node dysfunction ||Pacemaker usually required. |
|Pulmonary complications ||Diagnosis may require CT or more invasive diagnostic procedures. |
| Thromboembolic disease |
| Exercise-induced hypoxemia |
| Pneumothorax |
| Interstitial fibrosis |
|Cardiac ischemia ||Patients do not experience pain due to denervation; symptoms typically occur with complications such as congestive heart failure. |
|Rejection ||Treat the patient presenting in extremis; withhold treatment for biopsy if possible. |
|Infection ||See section "Posttransplant Infections" |
|Congestive heart failure ||Echocardiography can help to determine etiology and therefore ideal treatment. |
|Ischemic stroke and intracranial hemorrhage ||Increased risk after heart transplant. |
|Complications specific to ventricular assist devices ||Increased risk of infection and thromboembolism. |
|Cardiac allographic vasculopathy ||Pediatric heart transplant recipients are at risk for graft coronary artery disease and ischemia. May require retransplantation. |
ECG in a heart transplant patient. ECG demonstrates donor and recipient P waves (arrowhead = donor P wave; arrow = recipient P wave).
Chest radiograph of healthy post–heart transplant patient with typical postoperative changes, including "cardiomegaly" due to transplantation of a heart from a donor who was larger than the recipient.
Corneal transplantation (penetrating keratoplasty) is the most common form of human solid tissue transplantation. Unlike other tissue and organ transplants, corneal allotransplantation usually does not require systemic or permanent immunosuppression. Reasons for graft failure include corneal graft rejection (30.9%), corneal endothelial cell failure (21.0%), glaucoma (8.5%), and other causes (26.2%).37,38 Ophthalmology consultation is required for any change in visual acuity or other ocular signs or symptoms in a patient with a corneal transplant.
Corneal graft rejection is a specific process in which a graft that has been clear suddenly develops graft edema with anterior segment inflammatory signs. Rejection can occur at any time starting at 10 days after transplant. The inflammatory process starts at the graft margin nearest to the most proximal blood vessels and then moves toward the center to involve the entire graft.37 Signs and symptoms include eye pain, photophobia, corneal or scleral injection, or decreased visual acuity. Examination may reveal unilateral anterior chamber reaction with keratic precipitate or corneal edema in a previously clear graft. Late graft failure can present with gradual onset of graft edema with no associated inflammation or keratic precipitates. Treatment includes topical or systemic steroids, cycloplegics, and immunosuppressive drugs such as local and systemic cyclosporine A and tacrolimus.
Wound dehiscence can occur early or late after corneal transplantation, as a result of infection or after eye trauma. Trauma may be unrecognized or be a result of events such as motor vehicle airbag deployment or a fall with the patient's glasses impacting the eye. There may be globe rupture, slight separation of part of the suture line, or just broken sutures.
Viral,37 bacterial,39 or fungal40 infection can threaten the transplanted cornea. In patients with a history of herpetic keratitis, consider recurrence and examine with fluorescein for characteristic corneal staining and signs of anterior chamber inflammation.37 Ophthalmology consultation is needed for diagnosis and treatment.