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Incidence and Prevalence Estimates

• Solid organ transplants:
  
  • End of 2007: 183,222 living transplant patients
    
  • 27,281 organs transplanted in 2008
    
  • Most transplanted organs: Kidney (59%), liver (21%), heart (8%), lung (5%), pancreas (4%)
    
  • Most common diagnosis from visit to ED: Infection (36%), GI/GU pathology (20%), dehydration (15%), electrolyte (10%), CV and pulmonary pathology (10%), injury (8%), rejection (6%). 60% required hospitalization
    
• Hematopoietic stem cell transplants:
  
  • 4,300 transplants in 2008
    
  • Acute graft-versus-host disease incidence: 20–80%.
    

• Reduction or noncompliance with medication:
  
  • Medication interactions with cyclosporine, tacrolimus, or sirolimus:
    
    • Phenobarbital, phenytoin, carbamazepine, rifampin, isoniazid
      
• Kidney transplant rejection:
  
  • Early rejection caused by T and B lymphocytes, which attack microvasculature and impair graft perfusion; volume depletion, hypotension, infection
    
  • Chronic rejection caused by progressive nephrosclerosis of renal vessels, infection
    
• Liver transplant rejection:
  
  • Acute: 48% by 6 wk, 65% by 1 yr
    
    • Commonly follows reduction in the IS regimen
      
  • Chronic: <5%
    
    • 1 wk to 6 mo MC range to experience
      
• Cardiac transplant rejection:
  
  • Acute rejection:
    
    • 75–85% of patients within the 1st 3–6 mo due to T-cell–mediated response
      
  • Chronic rejection:
    
    • Accelerated atherosclerosis is the hallmark
      
    • Associated with change in IS therapy
      
• Lung transplant rejection:
  
  • Acute rejection develops early:
    
    • Can occur up to 6 times in the 1st year
      
  • Chronic rejection:
    
    • 25–40% of patients postop
      
    • MCC of death in 2nd postop year
      
    • Rejection caused by endothelial, vascular, and lymphocyte inflammation, recurrent acute rejection
      
• Bone marrow transplant rejection:
  
  • Acute graft-versus-host disease:
    
    • Immune attack of donor marrow on lung tissue
      
  • Chronic graft-versus-host disease:
    
    • 25–50% of patients
      
  • Marrow rejection:
    
    • MC in patients with plastic anemia who do not receive total body radiotherapy or in patients receiving mismatched or unrelated transplants
      

DIAGNOSIS

• Renal transplant rejection:
  
  • Progressive systemic HTN
    
  • Decreased urine output
    
  • Swelling, fever, and tenderness:
    
  • Uncommon with IS therapy
    
• Liver transplant rejection:
  
  • Fever, RUQ pain, jaundice
    
• Heart transplant rejection:
  
  • Fever, dyspnea, chest pain, hypo- or hypertension, palpitations, nausea, vomiting, syncope, sudden death
    
  • Can be asymptomatic
    
• Lung transplant rejection:
  
  • Cough, dyspnea, fever, rales, and rhonchi
    
• Bone marrow transplant rejection:
  
  • Fever, wasting, mucositis, keratoconjunctivitis, dysphagia, cough, dyspnea, hypoxia, chest pain, abdominal pain, diarrhea, jaundice, rash, encephalopathy, seizures
    

• CBC
  
• IS medication levels:
  
  • Levels may not represent through if patient took medication prior to ED visit.
    
• Blood cultures
  
• Renal transplant rejection:
  
  • Electrolytes, BUN, creatinine, CRP
    
  • Urinalysis with micro:
    
    • Proteinuria may signal early rejection. Presence of leukocytes may be seen during rejection as well as with infection.
      
    • FENa helps differentiate rejection from iatrogenic causes
      
• Liver transplant rejection:
  
  • Coagulation panel, lipase, cultures (blood, urine, ascites), liver function tests
    
  • Late acute rejection presents with elevated bilirubin and transaminases.
    
• Heart transplant rejection:
  
  • Cardiac troponin
    
• Lung transplant rejection:
  
  • ABG, electrolytes, kidney function, CRP, liver function, bilirubin, LDH, CPK, EBV, CMV, cyclosporine levels
    
• Bone marrow transplant rejection:
  
  • ABG, liver function tests
    

• CXR:
  
  • Acute lung rejection:
    
    • Diffuse infiltrates are seen early
      
    • Normal or unchanged >1 mo after transplantation
      
  • Bone marrow transplant rejection:
    
    • Interstitial infiltrates, pleural effusion, pulmonary edema
      
• Renal US:
  
  • Indicated for suspicion of renal transplant rejection:
    
    • Hydronephrosis implies obstructive uropathy and may need urgent percutaneous nephrostomy.
      
• Liver transplant:
  
  • Hepatic US
    
  • CT abdomen
    
• Echocardiography:
  
  • Heart transplant
    
    • Assess for changes in cardiac output.
      
• MRI:
  
  • Renal transplant:
    
    • May be done with or without contrast
      
    • Consult transplant team before giving contrast
      

• Liver transplant rejection:
  
  • ERCP cholangiography
    
• Heart transplant rejection:
  
  • EKG:
    
    • Commonly demonstrates 2 P waves because the native sinus node is spared
      
• Lung transplant rejection:
  
  • Peak flow reduced FEV1
    
  • Early bronchoscopy and biopsy to differentiate infection from rejection
    

• Consider drug toxicity and infection as well as rejection.
  
• Ask about medication dose or compliance changes
  
• Low threshold for screening labs and imaging even with minimal signs and symptoms
  

• Infections:
  
  • Wide variety of bacterial, mycobacterial, fungal, viral, and parasitic pathogens can cause opportunistic infections in transplant patients.
    
• IS toxicity
  
• Drug interactions with IS medication
  
• Renal transplant rejection:
  
  • Any disorder that can affect the native kidneys can also occur in the transplant
    
  • Iatrogenic nephrotoxicity: Cyclosporine, tacrolimus, other medications
    
  • UTI/pyelonephritis:
    
    • Classic organisms as with native kidney infections
      
    • Tubulointerstitial nephritis caused by the BK-polyomavirus (incidence 3–5%)
      
  • Acute occlusion of the transplant renal artery or vein:
    
    • Acute occlusion usually occurs within the 1st post-transplant week (incidence 0.5–8%) and causes oliguria and acute renal failure.
      
  • Peritransplant hematoma
    
  • Urinary leak
    
  • Obstructive uropathy
    
  • Bleeding after renal graft biopsy
    
• Liver transplant rejection
  
  • Ascending cholangitis:
    
    • Possible from colonized postop biliary stent.
      
  • Cholestatic hepatitis from azathioprine
    
  • Methotrexate-induced hepatotoxicity
    
• Lung transplant rejection
  
  • MC bacterial infection in lung transplant is cytomegalovirus pneumonia.
    
  • MC fungal infection is Aspergillus.
    
  • Upper respiratory infection or bronchitis:
    
    • Mimic chronic lung rejection
      
  • Medication-induced pneumonitis
    

TREATMENT

Avoid aggressive fluid resuscitation.

• ABCs
  
• Shock state treated with IV fluids, and pressor agents.
  
• Treat hypertensive crisis like other hypertensive emergencies.
  

• Kidney, heart, lung, and liver rejection:
  
  • Administer high-dose steroids
    
  • Stress-dose corticosteroid coverage is also indicated in any ill-appearing transplant patient. Consult with transplant service early
    
  • Avoid blood transfusions because these need special screening to prevent transmission of disease.
    
• Heart transplant rejection:
  
  • Pressors and inotropics work as usual in the transplanted heart.
    
  • Atropine will have no effect on bradycardia because there is no vagal innervation.
    
  • Use dopamine, epinephrine drips, or external pacing to increase heart rate if bradycardia is symptomatic.
    
  • IV methylprednisolone: 1 gm/d for 3 days
    
• Lung transplant:
  
  • Treat for infection and rejection
    
  • IV methylprednisolone: 15 mg/kg daily × 3 days
    
• Graft-versus-host disease:
  
  • 1–2 mg/kg daily PO or IV steroids
    
  • For chronic, may need adjustments of IS therapy.
    
• Common IS regimens are cyclosporine, prednisone, and azathioprine or tacrolimus and prednisone.
  

As directed by transplant team

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