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

Graft vs Host Disease (GVHD) is opposite of transplant rejection (i.e., graft against host). It is the reaction of donor immune cells in transplanted graft to host cells in immunocompromised patients. It is a type IV hypersensitivity reaction and frequently occurs in bone marrow and liver transplant (rich in lymphocytes).

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