Transplant Flashcards

1
Q

What is the rationale for kidney transplant?

What factors are considered when evaluating someone for a kidney transplant?

A
  • solid organ transplantation is a well established treatment for end stage organ failure
  • (liver, kidney, pancreas, heart, lung, also SB)
  • success due to advances in: surgical technique, peri-op care, imunosuppression, infectious diseases
  • kidney transplant is more cost-effective than dialysis and improves patient survival and quality of life

General evaluation of potential recipients for organ transplant:

  • evaluation by appropriate MDT incl surgeon & physician
  • determine presence of comorbid disease
  • exclude malignancy & systemic sepsis
    • even after curative tx for malignancy, transplant shouldn’t usually be considered for at least 3yrs
  • evaluate against organ-specific criteria for transplantation
  • evluate need for any preparative surgery to facilitate transplantation
    • ?parathyroidectomy
    • only when there is intractable renal sepsis or v large polycystic kidneys that intrude into both iliac fossae is native nephrectomy required before transplantation
  • optimise recipient condition before transplantation
  • determine probable ability to cope psychologically w transplant & comply w immunosuppression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How is tissue rejection classified?

A

There are three classic histopathological definitions of allograft rejection that are based on not only the predominant mediator, but also the timing of the process.

  1. Hyper-acute rejection
    • Mediated by pre-formed antibodies (ABO blood group incompatible or preformed anti-HLA antibodies)
    • After revasc of the graft, antibodies bind immediately to the vasculature, activate the complement system and cause extensive intravascular thrombosis, interstitial haemorrhage and graft destruction within minutes-hours
    • Prevented almost universally by lymphocytotoxic crossmatch
    • Irreversable
  2. Acute rejection
    • Occurs within first 6months
    • Mediated by T-cells - may be cell-mediated, antibody mediated or both
    • Reversable if promptly treated (most episodes of acute cellular rejection can be reversed by additional immunosuppressive therapy but antibody-mediated rejection more difficult to treat effectively; may require plasmaphoresis or immunoadsorption)
  3. Chronic rejection
    • ?​Term replaced by histological descriptors of long-term damage to transplanted organs
    • Occurs after 6months; causes functional deterioration in graft –> complete graft failure after months or years (currently available immunosuppressive therapy has little effect in preventing this)
    • most common cause of graft failure
    • pathophys not well understood but alloantibodies play a role and non-immune factosr contribute to pathogenesis; risk factors are previous episodes of acute rejection (most important), poor HLA match, long cold ischaemia time, CMV infection, raised blood lipids, inadequate immunosuppression (incl poor compliance)
    • characterised by myointimal proliferation in graft arteries leading to ischaemia adn fibrosis; in addition to vasculopathy there are organ-specific features of chronic graft rejection
      • kidney: glomerular sclerosis & tubular atrophy
      • pancreas: acinar loss & islet destruction
      • heart: accelerated coronary artery disease
      • liver: vanishing bile duct syndrome
      • lungs: obliterative bronchiolitis

The Banff classification is a thorough and widely used method of categorising the type of rejection via terms regarding the driving immune-mediator as well as precise histological criteria for each organ.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How are immunosuppressive medications classified with regard to phase of treatment?

A
  • Induction immunosuppression
    • Used for initial conditioning of the hosts immune system
  • Maintenance immunosuppression
    • Used to prevent minimise rejection following induction
  • Rescue immunosuppression
    • Used to reverse an acute rejection episode
    • Anti-thymocyte antiglobulins, human, rabbit, or horse dervied antibodies against T cells.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Provide an overview regarding risk of malignant disease in transplant patients.

A
  • The immune system plays a critical role in the identification and destruction of cancer; in particular cancer driven by viral infection
  • There is a 10-fold increase in cancer risk in transplant recipients
    • 40% of renal TPs get cancer within 20 years
    • 25% of TP deaths after 10 years
  • Skin cancer are the most common cause of morbidity and mortality
    • More aggressive cf non-TP patients
    • mostly SCC but BCC & melanoma also more common
    • 50% TP pts get skin cancer within 20yrs transplant
  • Virally mediated cancers also occur much more frequently
    • HPV; Anal, Cervical, Vaginal SCC
    • HBV and HCV; HCC
    • HHV8; Kaposi sarcoma (300x increased risk but still v uncommon)
    • EBV; Post Transplant Lymphoproliferative Disorder
      • presents in a variety of ways incl infectious mononucleosis-type illness or oymphadenopathy, or w involvement of extranodal sites eg tonsils, GIT, lung, liver or transplanted organ
      • occcurs in 1-3% of kidney & liver transplants, much higher incidence in children
      • mortality up to 50%
      • if identified early, reduction/cessation of immunosuppressive therapy may cause disease regression & cure; chemo often given and antiviral therapy, surgery and rad may also have a role in treating established disease
  • other cancers:
    • mild risk (RR2): colon, lung, prostate, gastric, oesophagus, pancreas, ovarian, breast
    • mild risk (RR4): testes adn urinary bladder
    • mod risk (RR5): melanoma, leukaemia, liver, gynae tumours
    • mod-high risk (RR15): kidney
    • high risk (RR>20): Kaposi’s sarcoma, PTLD, non-melanoma skin cancer
  • aetiology multifactorial
    • can be de novo, transmitted or reactivated with immunosuppression/recurrence of pre-existing malignancy
    • a combo of impaired immune activity against viruses, impaired immune-surveillance of neoplastic cells, DNA damage and disruption of DNA repair mechanisms, and upregulation of cytokines that can promote tumour progression
    • immmunosuppression - increased dose/intensity increases risk
      • anti-T-cell treatment particularly increases risk of EBV-associated PTLD
      • calcineurin inhibitors increase TGF-beta which ultimately stimulates tumour growth
    • exposure to carcinogens
      • UV shown to have effect both before & after transplant
    • host factors
      • genetics play a role
      • co-existence of viral infections, EBV, HSV8 for example that may have been dormant
  • strategies
    • prevention
      • avoid carcinogens - espec true for skin cancers & avoidance of UV radiation
      • avoid excessive immunosuppression - dose response for all transplant pts & all immunosuppressive therapies
      • avoid repeated exposure to depleting anti-lymphocytic antibodies
      • screen all donors & recipients for cancer
      • screen all donors & recipients for HSV8, EBV to minimise Kaposi’s and PTLD respectively
        • if positive recipient, measure EBV titres & adjust immunosuppression if increasing
    • early detection - screen recipients regularly for malignancy
      • including skin check q6-12mo and good pt education
      • if PTLD identified early, reduction/cessation of immunosuppressive therapy may cause disease regression & cure
    • management
      • prompt and aggressive management of malignancies - eg skin cancer progresses more rapidly if immunosuppressed
      • reduce immunosuppression in PTLD
      • consider conversion to mTOR inhibitor in Kaposi’s - been shown to induce complete regression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Provide an overview regarding risk of infectious disease in transplant patients.

A

Transplantation medicine is constantly negotiating a balance of risk of rejection against risk of infection from immune-suppression.

  • Infections are more common in the immediate post-operative period due to the mandatory immune suppression; early recognition and aggressive treatment is essential
  • Donor-derived infections occur but are rare
  • These may be missed in the pre-operative screen due to false negative tests, latency of onset, or lack of seropositivity
    • CMV, HIV, Hep B, Hep C, TB, Trypanosoma cruzii, West nile virus, and rabies are candidate infections.
  • Recipient-derived infections are much more common
  • Reactivation of CMV, EBV, Herpes simplex, VZV, PCP, HIV, parasites, and fungi occur much more commonly than transferred infections.
  • The risk of reactivation is highest in the first 6-12 weeks post transplant
  • Prophylactic regimens may be used, for example CTMX for PCP.
  • Bacterial infection - risk highest during first month
    • similar to any pt undergoing major surgery - at risk in wound, resp tract, urinary tract - standard to give broad spec abx to cover periop period as prophylaxis against wound ix & poss bacterial contamination of donor organ
    • if prev TB, given chemoprophylaxis for 6-12mo post transplant
  • Viral infection - risk highest during first 6mo post transplant
    • CMV = most common
      • may be reactivation of latent infection or primary infection that can be transmitted by an organ from a CMV-pos donor
      • w/o prophylaxis, usu presents at 4-8wks with high swinging fever, lethargy, leukopenia
      • severity variable; clinical picture depends on organ system most affected; may present as pneumonia, GI disease, hepatitis, encephalitis, retinitis
      • severe = potentially fatal
      • prophyylaxis = antiviral agents; most common valganciclovir
      • dx of active CMV = PCR to detect viral DNA in whole blood & by histo exam of biopsy
      • tx = oral valganciclovir or IV ganciclovir
    • HSV also common
      • usu from reaction of latent infnection
      • mucocutaneous lesions round mouth & genitalia
      • topical acyclovir or if severe systemic antiviral therapy
    • BK virus = important cause of renal graft dysfunction
      • almost universal infection during childhood w latent infection in epithelium of urinary tract
      • only effective tx = to reduce level of immunosuppression to allow natural immune mechanism to regain control of virus
    • Herpes zoster virus common
      • reactivation of latent varicella-zoster - systemic antivirals
      • primary infection = otentially v serious but rare
  • Fungal infection - usu within first 3mo, need early dx and aggressive tx
    • pneumocystis jiroveci presents w resp sx
      • dx on bronchoalveolar lavage or lung biopsy
      • chemoprophylaxis highly effective, usu continued for up to 6mo after transplant
    • others incl Candida or Aspergillus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the major groups of immunosuppressive medications?

A
  1. Corticosteroids
    • Prevents transcription of NF-kß and downstream cytokines, and T-cell activity
    • Also inhibits phospholipase A2 (AA cascade)
  2. Anti-proliferative agents
    • Azathiprine and mycophenolate prevent lymphocyte proliferation by blocking purine metabolism/synthesis - mostly T-cell but also bone marrow etc.
    • Side effects: leukopenia, thrombocytopenia, HTN, GI symptoms and in azathioprine, hepatotoxicity
  3. Calcineurin inhibitors
    • Prevent activation of IL-2, which is essential for T-call matruation.
    • Calcineurin has a critical role in facilitating transcription of IL-2, the main T cell growth factor and other cytokines after T cell activation
    • Cyclosporin and Tacrolimus
    • Side effects: nephotoxicity (tacrolimus > cyclosporine), glucose intolerance, neurotoxicity (tacrolimus), hypertension and hyperlipidaemia, and in cyclosporin gingival hypertrophy and hirsutism
  4. Antibodies
    • Anti-CD25
      • blocks IL-2 receptor on T lymphocytes
      • commonly given at time of transplant to augment effects of calcineurin blockade during early post-transplant period
      • side-effects uncommon
    • ALG
      • polyclonal antibody - antilymphocyte globulin
      • infusion reactions, leucopenia, thrombocytopenia
    • anti-CD52
      • ​monoclonal antibody against CD52 expressed on T cells & dendritic cells
      • infusion reactions, autoimmune disease
    • **ALG and anti-CD52 also widely used as more potent & alternative induction agents. These 3 cause temporary depletion in circulating lymphocytes that reduces rejection but may increase infection and malignancy
      • as well as use as induction agents, may be used to treat acute rejection episodes that don’t respond to steroids
    • anti-CD20 - rituximab
      • monoclonal antibody, depletes B lymphocytes
      • widely used in protocols to enable ABO & HLA incompatible renal transplants & also may be helpful in antibody-mediated acute rejection
      • infusion reactions, pulmonary toxicity
    • Monoclonal (OKT3) agents target CD3 antigen and lead to T-cell depletion
    • Polyclonal (thymoglobulin) agents causes idespread T-cell inactivation
  5. Other
    • ​​Target of rapamycin (mTOR) inhibitors
      • sirolimus and everolimus
      • inhibit IL-2 induced T-lymphocyte proliferation (sometimes switch from CNI to these to minimise CNI-induced nephrotoxicity)
      • thrombocytopenia, hyperlipidaemia, pneumonitis, impaired wound healing
    • ​CTLA-41g
      • ​prevent full T cell activation (alternative to CNI)
      • ​?increased risk of PTLD
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the steps involved in donation after circulatory death?

A
  1. Consensus by treating team that withdrawal of intensive therapies (ETT, inotropes etc) not compatible with life
  2. Discussion with transplant centre about suitability of DCD
  3. Consensus by treating team that intensive therapies will be withdrawn
  4. Disucssion of DCD with the family
  5. Family agreement (coroner also if needed)
  6. Withdrawal of intensive therapies
  7. Determination of death
  8. Organ retrieval after death.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the assessment of a live kidney donor

A

Comprehensive

Medical, Surgical, Psychosocial assessments including:

  • 24 hour ambulatory BP monitoring
  • 24 hour urine collect for creatinine
  • Nuclear medicine estimation of GFR
  • CTA for anatomy.

Traditionally most living-donor transplants were between genetically related individuals, but living-donor kidney tranpslants performed between genetically unrelated individuals also fare better than even well-matched deceased donor grafts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the risks of live kidney donation?

A
  • Risks attendant to lap nephrectomy
  • 3 in 1000 donors will go onto develop ESKD
    • Usually due to systemic disease that affects both kidneys anyway so
    • Only ~1 in 10,000 develop ESKD that they otherwise would not have developed.
  • 1 in 5000 death
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the mortality rates for live organ donation?

A

Kidney donor = 1/5000 (major complication rate <5%)

Left liver lobe donor = 1/1000

Right liver lobe donor = 1/300

(major complication rate for liver donor up to 15%, bile leak one of more common)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the side effects of corticosteroids?

A
  • Diabetes
  • Cataracts
  • Hypertension
  • Bruising
  • Striae
  • Cushingoid appearance (moon face; buffalo hump)
  • Psychoses
  • GI irritation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Classify the different types of transplant.

A
  • Xenograft
    • Transfer of organs from one species to another
  • Allograft
    • Transfer of organs between members of the same species
  • Isograft
    • Transfer of organs between identical twins
  • Autograft
    • Transfer of organs within the same individual
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the factors affecting success of solid organ transplant?

A
  • Donor factors
    • live related > live unrelated > deceased donor
    • Younger donor age
    • Donor comorbidity affects success rates
  • Recipient factors
    • Previous rejection is very bad
    • Length of time of dialysis is proportional to failure - if transplanted before starting dialysis, graft has 70% survival at 10yrs vs 50% at 10yrs
    • Worse comorbidities confer worse prognosis
  • Operative/technical factors
    • Cold ischaemic time
    • Warm ischaemic time
    • Preservation method
    • Reperfusion injury
    • Compromised inflow/outflow
  • Post-operative factors
    • Immunosuppression
    • Compliance
    • Secondary malignancies
    • Early recognition of rejection - salvage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the sources of transplanted organs?

A
  • Deceased donor (multi-organ)
    • After brain death (brain-stem dead, heart-beating donors)
    • After cardiac death
  • Live donor (single organ)
    • Risk to donor!
  • living donation limited to kidney and to much lesser extent, liver or lung lobe
  • DBD provide most of organs for transplant for all other types, though DCD donors provide increasing numbers of kidneys, livers, pancreas glands & lungs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How is brain-death diagnosed?

A

Brain death occurs when severe brain injury causes irreversible loss of capacity for consciousness combined with irreversible loss of capacity of breathing. In many countries brain death is defined in terms of permanent functional death of the brainstem as neither consciousness nor spontaneous respiration is possible in absence of a functional brain stem.

The medicolegal definition of brain-death varies between states and countries within Australasia, however some principles remain constant;

  • The diagnosis must be made by two specialist consultants, neither of whom are members of the transplant team
  • The patient must be comatose requiring ventilator support and all reversible physiological causes must have been addressed
    • ensure muscle relaxant agents & drugs with known CNS depressant effects aren’t contributing to clinical picture
    • hypothermia, profound hypotension & metabolic or hormonal conditions as contributors excluded
  • There must be a CNS catastrophe that is compatible with the patient’s state and of known aetiology

Examination must demonstrate absence of:

  • cranial nerve reflexes - pupillary reflex, corneal reflex, pharyngeal (gag) and tracheal (cough) reflex, oculovestibular (caloric) reflex
  • motor response - to painful stimuli applied to head/face and absence of motor response within cranial nerve distribution to adeqaute stimulation of any somatic area
  • spontaneous respiration - disconnected from ventilator for 10 minutes after pre-ventilating with 100% oxygen

(Radiological diagnoses may be made with absent flow on brain CTA.)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How is “brain death” determined in Australia and New Zealand?

A

Before testing can begin other causes of deep coma must be ruled out. There must also be a minimum of four hours observation and mechanical ventilation, during which the patient is completely unresponsive to all stimuli.

Must be carried out independently by two medical practitioners with experience and qualifications according to State laws.

  • 4 eye signs + pain + gag + breathing
    • Fixed and unresponsive pupils
    • Absent corneal reflexes
    • No oculo-cephalic reflexes
    • No vestibulo-ocular reflex
    • No pain reflex
    • No gag or cough
    • No respiratory efforts with high CO2
  • Can use imaging to determine loss of blood flow in special cases (facial trauma ++)
17
Q

How can shortages of organs for transplantation be overcome?

A
  • maximising DBD (donation after brain death) donation
  • use of marginal DBD donors
  • use of donation after circulatory death (DCD) donors
  • increased use of split-liver transplantation (right lobe into adult, part (even just segment 2) into child)
  • increased living donor kidney (and liver) transplantation; options are
    • standard transplant
    • paired kidney exchange
    • ABO incompatible - transient depletion of ABO antibodies from potential recipients by passing their blood through special absorption columns or by performing plasmaphoresis along w admin of pre-transplant immunosuppressive agents
      • graft outcome after desensitisation similar to after paired exchange
    • altruistic donor
  • countries have different approaches to referral/consent
    • in some countries all pts dying in ICU have to be referred for their potential suitability to be an organ donor to be assessed
    • some have ‘opt out’ systems - unless specifically registered objection before death
18
Q

What is donation after circulatory death and how are such donors categorised?

A
  • donation after circulatory arrest and death, previously called non-heart-beating-donation
  • 5 Maastricht categories of DCD:
    • category 1: dead on arrival at hospital
    • category 2: resuscitation attempted w/o success
    • category 3: ‘awaiting cardiac arrest’ after withdrawal of support
    • category 4: cardiac arrest while brain dea
    • category 5: cardiac arrest and unsuccessful resus in hospital
  • categories 1, 2 and 5 sometimes referred to as uncontrolled DCD donors
    • warm ischaemic time of organs from these 3 categories of donor usu longer & less predictable than in the case of categories 3&4 (controlled) donors
    • most DCD donors are category 3; may also use carefully selected cat 1 or 2/5 pts (in Spain & France most DCD kidneys from uncontrolled donors)
  • in Aus & NZ, DCD can occur after a decision has been made to withdraw treatment bc it is considered no longer to be in the person’s best interest; this decision is usually reached by healthcare staff and family, though in v rare and exceptional circumstances the decision may be made by the conscious, competent patient
    • situations where it’s considered include severe brain injury that hans’t and isn’t likely to progress to brain death, end-stage cardio-resp or other organ failure, high spinal cord injury & progressive neuro-muscular conditions
    • most of these in ICU on ventilation; if cardiac standstill, and thus death, occurs within a short timeframe after withdrawal of cardio-resp supportive treatment (generally within 60-90mins (liver 30, lungs/kidneys 90mins), donated organs can be transplanted with success (~70% die within this timeframe)
19
Q

Evaluation of deceased donor

A
  • no absolute age restriction
  • satisfactory organ function
  • no serious transmissible disease
    • some viral infections ok - would use hep C liver these days as long as not cirrhotic bc can cure them post-op
      • can use hep B positive too - just have to keep them on suppressive tx
      • HIV only if going into HIV positive recipient
    • no untreated bacterial sepsis
    • no malignancy (except primary cerebral maliganncy - doesn’t cross BBB, non melanotic skin cancer & carcinoma in situ of cervix)
  • use of marginal donors been increased bc of demande - definitioin of this depends on organ being considered & varies between countries
20
Q

What is warm ischaemic time?

A

Time between cardiorespiratory death and infiltration of chilled perfusate?

21
Q

Consent for live donor nephrectomy

A
  • now usually do lap (previously loin incision w retroperitoneal approach or through a midline abdo incision & transperitoneal approach)
    • lap = less wound pain, quicker mobilisation, shorter LOS
  • mortality 1 in 5000 (half from PE)
  • major complication rate <5%
    • complications include: haemorrhage requiring transfusion, infection (chest/abdo/renal tract/wound), damage to intra-abodminal structure, adverse rxn to drugs/anaesthesia, VTE)
  • in long term, may be at increased risk for HTN and need annual BP & urine check
  • 3 in 1000 donors will go onto develop ESKD
    • Usually due to systemic disease that affects both kidneys anyway so
    • Only ~1 in 10,000 develop ESKD that they otherwise would not have developed.
22
Q

Technical complications in renal transplant

A
  • vascular complications
    • renal artery thrombosis - 1%
    • renal vein thrombosis - up to 5%
      • presents during first week after transplantation w sudden pain & swelling at graft site
      • dx confirmed by Doppler USS
      • urgent surgical exploration; in most cases transplant nephrectomy required
      • incidence can be minimised by low-dose heparin or aspirin prophylaxis
    • renal artery stenosis - up to 10%
      • usu presents late (often yrs) after transplant with increasing HTN & decreasing renal function
      • dx by angiography
      • best tx = angioplasty; if fails surgical reconstruction
  • urological complications (can be decreased by leaving temporary ureteric stent)
    • urinary leaks
      • from technical errors at ureteric anastomosis or bc of ureteric ischaemia
      • discomfort & leakage of urine from wound
      • usu need surgical intervention & reimplantation of ureter into bladder or anastomosis of transplant ureter to ipsilateral native ureter
    • obstruction of transplant ureter - early or late
      • causes include technical error, external pressure from haematoma or lymphocele, ischaemic stricture
      • painless deterioration in graft fn
      • USS - hydronephrosis & ureteric dilatation on USS
      • initially tx by perc anterograde nephrostomy & insertion of stent
      • some ureteric stricture may be amenable to tx by balloon dailatation but most best tx by surgical intervention, reimplanting donor ureter into bladder or anastomosing it to native ureter
    • lymphocele
      • usu asymptomatic but may become large enough to cause ureteric obstruction or oedema of ipsilateral leg
      • USS-guided perc drainage
      • if large/recurrent may need to surgically drain into peritoneal cavity - can do USS-guided lap approach
23
Q

What are the early and late causes of allograft dysfunction?

A
  • early
    • primary non-function (irreversible ischaemic damage)
    • delayed function (reversible ischaemic injury)
      • ok for kidneys & SB & pancreas to have delayed function but need heart, lungs, liver to resume satisfactory function immediately
    • hyperacute and acute rejectoin
    • arterial or venous thrombosis of the graft vessels
    • drug toxicity (eg calcineurin inhibitor toxicity)
    • infection (eg CMV disease in graft)
    • mechanical obstruction (ureter/CBD)
  • latte
    • chronic rejection
    • arterial stenosis
    • recurrence of original disease in graft (glomerulonephritis, hep C)
    • mechanical obstruction (ureter, CBD)
24
Q

Investigation and management of renal graft dysfunction

A
  • early postop period graft dysfunction is common; possible causes:
    • acute tubular necrosis
      • delayed graft function (reversible ischaemic injury) (defined as a need for dialysis post-transplant) as a result of ATN occurs in 25% of kidneys from DBD & up to 50% of kidneys from DCD donors, but <5% after living donor transplants
      • ATN usu resolves within first 4wks but small number (<5%) have primary non-function - ie never function
    • arterial/venous thrombosis
    • urinary leak/obstruction
    • CNI toxicity
    • hyperacute/accelerated acute rejection
    • ?infection eg CMV in graft
  • management
    • irrigate urinary catheter in case occluded by blood clot
    • correct hypovolaemia if present
    • doppler USS of graft = v important - vasc thrombosis or urinary obstruction
    • renal radionuclide scanning provides info on renal perfusion & excretion, may be helpful but used infrequently
    • if graft dysfunction still present after several days: USS-guided needle biopsy to ensure graft rejection not present (then repeat ix every week or so til graft function improves)
    • CNI toxicity may cause graft dysfunction - monitor levels to avoid nephrotoxicity
  • late allograft dysfunction (>1mo after transplant)
    • acute/chronic rejection
    • arterial stenosis
    • ureteric obstruction (lymphocele/ureteric stricture)
    • recurrent disease
    • UTI
  • mx of late dysfunction:
    • check CNI levels
    • USS graft +/- perc antegrade urography to further ix if obstruction present
    • if uncertain re cause of graft dysfunction, transplant biopsy to establish whether allograft rejection present
25
Q

Outcomes after transplant

A
  • pt survival after deceased renal transplant >95% at 1yr, >85% at 5yrs
  • graft survival
    • after deceased renal transplant 90% 1yr, 80% 5yrs
    • after LR renal tranpslant 95% 1yr, 85% 5yrs

Graft survival after kidney, liver and heart transplantation = >90% at 1yr & 80% at 5yrs

Chronic rejection = most common cause of graft failure after all types of solid-organ transplant

Outcomes after liver transplant depend on underlying liver disease

  • best with chronic liver disease
  • those done for acute liver failure have higher early post-op mortality bc of multiorgan failure, but those who make satisfactory recovery have v good long-term liver allograft survival
  • those done for tumour - v good early outcome but ultimately fare much less well bc of recurrent malignancy
26
Q

What is the role of pancreas transplantation?

A
  • successful transplant restores normal control of glucose metabolism & obviates need for insulin therapy in pts w DM
  • improved control of BSLs in pts w diabetes decreases progression of secondary complications eg retinopathy, PVD, nephropathy - but have to weigh these against risks both of transplantation itself & immunosuppressive therapy required
  • for most pts w diabetes, additional risks assoc w panc transplant & immunosuppression means transplant only justified if kidney transplant for diabetic nephropathy also being done (though do need extra immunosuppression cf kidney transplant alone)
  • in US half pts w diabetes having kidney transplatn also get pancreas transplant (usu from same donor)
  • principal aim is to prolong life in pts w diabetes who otherwise have high mortality at 10yrs after receiving kidney transplant alone
  • also provides freedom from insulin tx & improves QOL
  • after SPK transplant, 1yr pt survival >95%, 1yr graft survival for panc 85% & kidney 95%
  • pt & kidney graft survival after SPK transplant in pts w diabetic neuropathy = at least as good as after kidney transplant alone in this group
27
Q

Indications for liver transplant

A

4 groups

  • cirrhosis
    • most common indication
    • in adults, most = alcoholic liver disease, viral liver disease (hep C, ehp B), NASH, PBC and sclerosing cholangitis
    • in children (10-15% all liver transplants) = biliary atresia
  • acute fulminant liver failure
    • this requiring urgent transplant = ~10% liver transplant activity, usu viral or drug induced
  • metabolic liver disease
    • eg Wilson’s, oxalosis
  • primary hepatic malignancy
    • more common in pts w cirrhosis espec virally induced disease; may be best tx by transplant bc field changes in cirrhotic liver predispose to further primary malignancies
    • cholangiocarcinoma has high recurrence rate & seldom an indication for liver transplantt
28
Q

Technical complications of liver transplant

A
  • haemorrhage
    • may need to pack peritransplant area for 2-3 days to achieve adequate haemostasis when diffuse oozing despite correction of coagulopathy
    • evacuation of extensive peir-hepatic haematoma may be required to avoid secondary infection
  • vascular complications
    • hepatic artery thrombosis
      • spontaneously or as a result of acute rejection
      • more common in PSC
      • may present as risk in serum transaminase levels, unexplained fever or bile leak
      • doppler USS or angiography to confirm dx & urgent retransplantation usu required
    • portal vein thrombosis - rare
      • presents w features of portal HTN
    • hepatic vein occlusion
      • often presents w increasing ascitic fluid losses over postop period
      • cavogram w hepatic vein pressure studies to confirm
      • treat with insertion of vasc stents, surgical correction or re-transplantation
  • biliary complications
    • biliary leaks now relatively uncommon
    • biliary stenosis more common
      • usu occurs within first few mo of transplant, managed by endoscopic dilatation & stenting or by surgical correction
29
Q

Give an overview of immunosuppressive regimens

A
  • aim: maximise graft protection w minimum of side effects
  • protocols use combo of agents acting at different points in the pathway of lymphocyte activation
  • most regimens: ‘triple therapy’
    • calcineurin inhibitor (often supplemented with anti-CD25 monoclonal antibody induction therapy)
    • antiproliferative agent (usu mycophenolate)
    • steroids
  • less commonly ‘double therapy’ with CNI and one of the other 2
  • acute rejection: short course high dose steroids
    • 2nd line if inadequate or recurs = ALG