Organ Transplant Complications and Rejection

Types of Transplant Rejection

Type	Time	Mechanism	Pathology	Hypersensitivity	Management
		Host against Graft (Host vs Graft)	Mnemonic: TIA
Hyperacute	Immediate (<5 days)	Anti-donor antibodies in recipient	Thrombosis and Obliteration of blood supply	Type II	Untreatable Prevent by cross-matching Remove graft
Acute (most common)	< 6 months (most common in 1st month)	Anti-donor T cell proliferation in recipient	Interstitial lymphocyte infiltrate	Type IV	Prevent/reverse with immunosuppressants
Chronic	Months to years (usually >6 months)	Development of multiple cellular and humoral immune reactions to donor vasculature	Arteriosclerosis and intimal fibrosis	Type III and IV	Unresponsive to immunosuppressants
Accelerated acute	First few days (7-10 days)	Activation of memory T and/or B lymphocytes in pre-sensitized receipients (post-formed CMI and antibodies)			May be responsive to antibody therapy: OKT3, ATG

Post-renal transplant fluid collections

Mnemonic: HEAL

1. Hematoma (Immediate)

2. Encapsulated urine collections/urinomas (1-2 weeks): commonest cause is ureter tip necrosis and may require revision anastomosis

3. Abscess (3-4 weeks)

4. Lymphocele (2 months)

Post-renal transplant renal injury

Mnemonic: SCRI

1. Structural causes: USG

• Renal artery thrombosis – Sudden complete loss of urine output (T/t: Immediate surgery within 30 minutes)
• Renal artery stenosis – Uncontrolled hypertension; allograft dysfunction and edema (T/t: Angioplasty)
• Renal vein thrombosis – Pain and swelling of graft site, hematuria and oliguria (Graft is usually lost)

2. Calcineurin inhibitor toxicity: Cyclosporin level

3. Rejection and/or Recurrence of primary disease: Biopsy (rejection type; MCGN>IgA nephropathy>FSGS)

4. Infection: PCR

• 1-6 months post-transplant: BK virus, CMV
• >6 months post-transplant: PTLD (Post-transplant lymphoproliferative disorder) – EBV

Outcomes

Transplant	1 year survival	5 year survival
Renal	90%	65%
Cardiac	80%	65%
Hepatic	80%	55%
Lung	70%	55%
Pancreatic	75%
Small bowel	60%

Immunosuppressants

Drugs	Mechanism	Adverse effects
Corticosteroids	Suppress all inflammatory elements of immune response	‘Cushingoid’ effects
Calcineurin inhibitors (Cyclosporin, Tacrolimus)	Suppress T-cells and inhibit IL-2 release	Nephrotoxicity (more with cyclosporin) Diabetes (with tacrolimus)
Anti-proliferatives (methotrexate, azathioprine, mycophenolate)	Prevent cell mediated cell mitosis and amplification of response	Renal and hepatic dysfunction, marrow suppression
mTOR inhibitors (sirolimus, rapamycin, everolimus)	Prevents T cell and B cell activation by blocking IL-2 receptors	Interstitial pneumonitis
Biologic effectors	Basiliximab: anti-IL2-receptor antibody Rituximab: anti-CD20 antibody	Cytokine release syndrome
Hydroxychloroquine (for chronic GVHD)	Inhibits antigen processing	Visual disturbances
Thalidomide (for chronic GVHD)	Inhibits T-cell function and migration	Sedation, constipation, teratogenicity