Kidney transplant complications

Background

• most commonly transplanted organ

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

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)

Clinical Features

The clinical features will depend on the type of complication and the amount of time elapsed post-transplantation.

Hyperacute Rejection

• Little or no urine output
• Widespread thrombosis

Early Complications

• Symptoms of infection
• Symptoms of recurrent disease
• Decreased urine output
• Hemorrhagic or non-hemorrhagic cystitis

Late Acute

• Symptoms of infection
• Symptoms of recurrent disease
• Decreased urine output
• Hemorrhagic or non-hemorrhagic cystitis

Late Chronic

• Symptoms of infection
• Symptoms of recurrent disease
• Decreased urine output
• Hemorrhagic or non-hemorrhagic cystitis

Infection

• May not have classic findings due to immunosupression
• Presentation depends on source of infection

Medication Adverse Effects

• Prednisone
  • Hyperglycemia, psychiatric symptoms, poor wound healing, edema, hypertension
• Tacrolimus, cyclosporine
  • Neurotoxicity, tremor, hyperkalemia, nephrotoxicity, hypertension, hyperglycemia, gout
• Mycophenolate
  • Cytopenias, GI distress
• Azathioprine
  • Cytopenias, pancreatitis, hepatitis

Differential Diagnosis

• Solid organ rejection
• Infection
• Medication side effect
  • Graft-versus-host disease
• Post-operative complications
• Diagnoses related to underlying disease or comorbidities

Evaluation

Depending on presentation, work-up may include:

• CBC
• BMP for BUN/creatinine
  • best prognostic marker of graft function
  • necessary to dose some empiric antibiotics
• Urinalysis (for infection and signs of rejection)
• Tacrolimus/cyclosporine levels
• Infectious work-up
  • Blood/urine cultures, PCR or other tests for viral/fungal infections as indicated
  • CXR
• consider renal ultrasound for workup of rejection

Management

• Empiric antimicrobials for suspected infection
  • See immunocompromised antibiotics
• Consult relevant transplant team
• High-dose steroids are usual therapy for rejection

See Also

• Transplant complications