S&P Lecture 4: Organ Transplant

How is brain death legally defined?

The irreversible cessation of brain function including the brainstem

Brain death requires the ABSENCE of which conditions that can mimic it?

Drug overdose, Medication side effects, Severe hypothermia, Hypoglycemia, Induced coma, Chronic vegetative state

How is brain death determined?

Through a clinical exam and associated ancillary tests

What are the four essential steps in the clinical diagnosis of brain death?

1. Establish the proximate cause of the neurologic insult

2. Clinical exams to determine coma and absent brainstem reflexes and apnea

3. Ancillary tests in patients who do not meet clinical criteria

4. Appropriate documentation

The clinical exam for brain death must establish which three findings?

Coma, Absence of brainstem reflexes, Apnea

Which ancillary tests are used for brain death when clinical criteria are not met?

EEG, Cerebral angiography, Nuclear scans

Once brain death has been determined who assumes care of the patient?

The local OPO (it also assumes financial responsibility)

Which patient is a candidate for donation after cardiac death (non-heart-beating donor)?

Devastating injury with no chance of meaningful recovery who does NOT meet brain death criteria

When is organ procurement done in donation after cardiac death?

With consent after withdrawal of life support and cessation of cardiac and respiratory function

What do viable organs recovered after cardiac death require?

Flushing with a cold preservation solution, Aortic cross clamping

What are the adult causes of end-stage renal disease listed for kidney transplant?

Diabetes, Hypertension, Glomerulonephritis, Cystic kidney disease

What are the top two causes of new adult ESRD and their percentages?

Diabetes (40-47%) then hypertension (29-35%)

What are the pediatric causes of ESRD?

Focal segmental glomerulosclerosis, Glomerulonephritis, Congenital anomalies

What GFR defines ESKD as the primary indication for kidney transplant?

GFR

Per KDIGO which CKD patients should be evaluated for kidney transplant and what is the goal?

All CKD stage G4-G5 (GFR

What are the absolute contraindications to kidney transplant?

Active or untreated malignancy, Severe uncorrectable cardiac or pulmonary or hepatic disease, Progressive neurodegenerative disorder, Ongoing or untreatable infection, Demonstrated nonadherence jeopardizing the graft, Transplant won't improve life expectancy or quality of life

What is the indication for a simultaneous pancreas-kidney (SPK) transplant?

Type 1 diabetes + ESRD

What is the indication for pancreas after kidney (PAK) transplant?

Type 1 diabetes with a prior kidney transplant and persistent poor glycemic control or severe metabolic complications

What is the indication for pancreas transplant alone (PTA)?

Type 1 diabetes with preserved renal function and incapacitating glycemic instability not manageable with intensive insulin

What are the three indications for liver transplant?

Acute liver failure (fulminant hepatic failure)

Decompensated cirrhosis with complications

Unresectable hepatocellular carcinoma

What is the most common indication for liver transplant?

Decompensated cirrhosis with complications

Which complications of decompensated cirrhosis are indications for liver transplant?

Refractory ascites, Hepatic encephalopathy, Variceal bleeding, Coagulopathy, Hypoalbuminemia, Hepatorenal syndrome

How is acute liver failure defined by time course?

Rapid (

When is acute liver failure an urgent indication for transplant?

When King's College or MELD criteria predict poor survival

Which HCC patients are liver transplant candidates and what do they receive?

Unresectable HCC within Milan or UNOS criteria (no vascular invasion or metastasis) — eligible for MELD exception points

What MELD or Child-Pugh score should trigger referral for liver transplant evaluation?

MELD >15 or Child-Pugh ≥9

How often is MELD-Na recalculated?

Every 7-30 days depending on disease severity

What is the primary indication for heart transplant?

Advanced (Stage D) heart failure refractory to GDMT and device therapy and surgical optimization

What NYHA class supports heart transplant?

Persistent NYHA class III-IV symptoms

What is the objective evidence of poor prognosis for heart transplant?

Peak VO₂ ≤14 mL/kg/min on CPET, Recurrent ventricular arrhythmias, Progressive end-organ dysfunction

Besides end-stage heart failure what other specific indications exist for heart transplant?

Refractory angina not amenable to other interventions, Life-threatening arrhythmias not amenable to other interventions, Failure of mechanical circulatory support (LVAD), Ineligible for durable device therapy

What are the contraindications to heart transplant?

Active infection or malignancy, Severe irreversible pulmonary or renal or hepatic disease, Significant non-adherence or lack of psychosocial support

What is the leading global indication for lung transplant?

Interstitial lung disease / idiopathic pulmonary fibrosis

Which findings define COPD severe enough for lung transplant?

FEV₁

What FEV₁ supports lung transplant in cystic fibrosis?

FEV₁

What life expectancy is a general criterion for lung transplant?

< 2 years (or severely reduced quality of life)

Which diseases are indications for lung transplant?

ILD / IPF, COPD / emphysema, Cystic fibrosis, Pulmonary arterial hypertension, Sarcoidosis, Fibrotic hypersensitivity pneumonitis, CTD-associated ILD

In adults short bowel syndrome leading to small bowel transplant is secondary to what?

Crohn's disease, Mesenteric vascular accidents, Trauma or surgical complications

What defines loss of central venous access as an indication for small bowel transplant?

Thrombosis of ≥2 major veins making PN delivery impossible or unsafe

What are the indications for small bowel transplant?

Intestinal failure-associated liver disease (from long-term PN), Loss of central venous access, Recurrent life-threatening catheter-related sepsis, Frequent severe dehydration despite PN, High risk of death from intestinal disease or nutritional failure, Large abdominal desmoid or intra-abdominal tumors with expected cure, Extensive mesenteric vein thrombosis, Total intestinal aganglionosis, Congenital secretory diarrhea

What compatibility labs are part of the pre-transplant evaluation?

ABO/Rh typing, HLA typing, Crossmatch

Which infections are on the pre-transplant viral screen (NAT required)?

HBV, HCV, HIV, CMV, EBV, HSV, VZV, Syphilis

When is endoscopy/colonoscopy part of the pre-transplant evaluation?

Age ≥50 or disease-specific risk

Which vaccinations are given pre-transplant?

Hepatitis A and B, Pneumococcal, Influenza (inactivated), COVID-19, Tdap, HPV (eligible ages), Meningococcal, Hib, MMR, Varicella

Which vaccines can be given ONLY pre-transplant and why?

MMR and varicella — they are live vaccines

What are the non-medical criteria for transplant candidacy?

Life expectancy, Potentially injurious behavior, Adherence, Repeat transplantation, Incarceration status, Immigration status, Social support, Pediatric/adolescent/young adult

Does citizenship or immigration status preclude listing for transplant in the U.S.?

No — UNOS/OPTN policy does not preclude non-citizens from being listed or transplanted

What percentage of a center's transplants can go to non-resident aliens?

Up to 5%

What are the primary barriers to transplant for a non-citizen patient?

Financial and logistical — often lack Medicare/Medicaid or private insurance for the transplant and lifelong immunosuppression

Does UNOS mandate 6 months of alcohol abstinence before liver transplant?

No — no national mandate — it relies on center-level multidisciplinary evaluation (the 6-month rule is now viewed as largely arbitrary)

What psychosocial criteria allow early liver transplant for severe alcoholic hepatitis?

Strong support system, Insight into addiction, Low risk of recidivism

A cirrhotic patient with 2 months of sobriety needs what before liver transplant?

Rigorous evaluation by addiction psychiatry — he is not automatically disqualified by UNOS

Does UNOS have a strict upper age limit for transplant?

No — but allocation requires a reasonable likelihood of post-transplant survival

An 85-year-old with EF 10% and colon cancer treated 5 years ago — what makes her ineligible?

Extreme age + severe cardiopulmonary compromise = absolute contraindication (unacceptable perioperative mortality) — the 5-year cancer-free status is NOT the barrier

Are incarcerated patients eligible for transplant and on what legal basis?

Yes — fully eligible — the Eighth Amendment guarantees equivalent care (denial = cruel and unusual punishment)

Who pays for an incarcerated patient's transplant?

The state or federal prison system (not Medicare)

What is the OPTN?

The national framework for organ donation policies and procedures (federally mandated)

What is UNOS?

The private nonprofit nongovernment contractor that operates the OPTN

What is an OPO?

The regional organ recovery agency

What is the median wait time for a kidney transplant?

~4 years (longest)

What is the median wait time for a lung transplant?

2-3 months (shortest)

What is the median wait time for a liver transplant?

1-1.5 years

What is the median wait time for a simultaneous pancreas-kidney transplant?

12-13.5 months

Which organs have a median wait time of

Heart, Small bowel, Lung

What are the steps in making a donor-recipient match?

Confirm ABO compatibility, HLA typing and antibody screening, Calculate cPRA, Test for DSA and crossmatch

What does the calculated panel-reactive antibody (cPRA) score quantify?

HLA sensitization

What causes HLA sensitization (raises cPRA)?

Prior pregnancies, Blood transfusions, Past transplants, Infections

Which kidney transplants have the best long-term outcomes?

"Zero mismatch" (more mismatches = higher rejection risk and shorter graft survival)

What percentage of waitlisted patients have anti-HLA antibodies?

Nearly 30%

DSA detected by CDC crossmatch means what?

Absolute contraindication (risk of hyperacute rejection)

What are the features of the flow cytometry crossmatch?

Done while the organ is being prepared, More sensitive than CDC crossmatch, Detects IgG DSA, Identifies antibodies even if they do not activate complement

How does a virtual crossmatch work?

Done before the recipient is notified — uses anti-HLA screening results + donor HLA typing to predict the crossmatch outcome without performing it

What type of organ donation system does the U.S. use?

Opt-in — you must actively register

What percentage of Americans support organ donation vs are registered?

80% support — only ~40% registered

What percentage of potential donors become actual organ donors?

30-40%

What is the order of the organ procurement process?

Hospital identification → notify OPO → brain death declaration → medical evaluation → consent

How long does tissue typing take?

About 6 hours

What is warm ischemic time?

Time an organ remains at body temperature after its blood supply has been stopped or reduced

What is cold ischemic time?

Time an organ is chilled and not receiving a blood supply

What is the cold ischemia time for a heart?

4 hours (shortest)

What is the cold ischemia time for lungs?

4-6 hours

What is the cold ischemia time for a liver?

6-10 hours

What is the cold ischemia time for a pancreas?

12-18 hours

What is the cold ischemia time for intestines?

6-12 hours

What is the cold ischemia time for kidneys?

24 hours (up to 72 hours on a perfusion pump)

What does the preservation solution do to the organ's metabolism?

Slows but does not halt metabolic activity (storage lasts hours not days)

What are the negative effects of organ preservation solution?

Cellular swelling, Degradation

What is the operating time for a renal transplant?

2-4 hours

What is the operating time for a pancreas transplant?

3 hours

What is the operating time for a liver transplant?

6-12 hours

What is the operating time for a heart transplant?

4-9 hours

What is the operating time for a lung transplant?

Single 4-8 hours — double 6-12 hours

What is the operating time for a small bowel transplant?

8-10 hours

In which transplants is the native organ NOT removed?

Kidney, Pancreas

Where is a renal transplant graft placed?

Extraperitoneally in the iliac fossa — most commonly the right side

How is the transplanted ureter attached and when is the stent removed?

Ureteroneocystostomy over a ureteric stent — removed around 6 weeks

Why can a pancreas transplant cause systemic hyperinsulinemia?

Venous drainage into the IVC lets insulin bypass hepatic first-pass metabolism

What is the difference between the two hepatectomy techniques in liver transplant?

Classic = excises recipient IVC — piggyback = preserves the IVC

What are the two LVAD options available to the heart failure patient?

Bridge-to-transplant, Destination therapy

What PEEP and tidal volume are used for fragile donor lungs?

PEEP