Transplant complications

Background

• Transplanted organ frequency: kidney > liver > heart > lung > pancreas > other (combined and intestines)
• Most transplant patients require lifelong immunosuppression

Types of Transplant complications

Immediate (0-1 week)

• Acute Tubular Necrosis
  • May be post-ischemic, commonly effecting both the proximal tubules and the thick ascending limb. Or it may be immunosupresive drug induced and only effect the proximal tubules. Granular "muddy brown asts" seen on urinalysis result from death and sloughing of tubular cells.
• Antibody mediated rejection
  • Results from donor specific antibodies including as ABO isoagglutinins.
  • Usually results in graft loss within 24 hours.
• Embolization and Thrombosis
  • May arise with or without rejection
  • May result from hypotension, anastomotic stenosis, arterial dissection, kinking of transplanted artery, or angulation of the vein
• Calcium Oxalate deposition
• Delayed graft function
  • This is defined as renal failure persisting after transplantation necessitating dialysis. It my be due to post-ischemic acute tubular necrosis, volume depletion, or volume depletion.
• Urinary bladder dysfunction
  • This complication is especially common in diabetics and may cause hydronephrosis

Early (1-12 weeks)

• Acute rejection
  • Antibodies against donor kidney develop after transplant
  • Dense interstitial lymphocytic infiltrate
  • Prevent/reverse with immunosuppressants
• Immunosuppressive Cytotoxicity
  • Usually caused by calcineurin inhibitor toxicity
  • Reverse by decrease dosage of immunosuppressants
• Infection
  • Most commonly polyoma (BK virus) or cytomegalovirus (CMV)
  • Polyoma virus is treated with intravenous immunoglobulins
  • CMV is treated with antivirals medications
• Recurrence of primary disease

Late Acute (greater than 3 months)

• Hypertension
  • Hypertension is common in ESRD/CKD patients and often worsens after transplant
  • Can result in decreased allograft survival
• Renal artery stenosis
  • Important to identify because is a correctible cause of post-transplant hypertension
• Acute Rejection
  • Same as above
• Immunosuppressive cytotoxicity
  • Same as above

Late Chronic (years later)

• Chronic allograft nephropathy
  • Irreversible T-cell and antibody mediated damage
  • Causes vascular fibrosis
• Immunosuppressive cytotoxicity
  • Same as above

Epidemiology

• Types of presentations
  • Infection (39%)
  • Noninfectious GI/GU pathology (15%)
  • Dehydration (15%)
  • Electrolyte disturbances (10%)
  • Cardiopulmonary pathology (10%)
  • Injury (8%)
  • Rejection (6%)
• Acute graft-versus-host disease occurs in 20% to 80% of patients post-hematopoietic stem cell transplantation (HSCT); rarely occurs in solid organ transplant

Immunosuppressant Medications

• Balance between immune suppression, rejection and susceptibility to infection
• Typical regimen includes: calcineurin inhibitor + antimetabolite + steroid
  • Calcineurin inhibitor
    • Cyclosporine
    • Tacrolimus
  • Steroids
    • Prednisone/Prednisolone
  • +/- Antimetabolite
    • Azathioprine
    • Mycophenolate mofetil (MMF)

Types

• Graft-vs-host disease
• Kidney transplant complications
• Liver transplant complications
• Heart transplant complications
• Lung transplant complications
• Pancreas transplant complications