Living related recipient workup- CPG

37. LIVING RELATED RECIPIENT WORKUP

37.1 Contraindications to transplantation
37.1.1 HIV infection1,2 (Level C)

37.1.2 Malignancy (Table 37.1)3

Table 37.1: Guidelines for recommending tumor free waiting periods for common pretransplant malignancies3
Site Waiting period
Renal: Incidental, asymptomatic None
Large , infiltrating At least 2 years
Wilm’s tumor At least 2 years
Bladder : In situ None
Invasive At least 2 years
Uterus : In situ cervical None
Invasive cervical 5 years
Uterine body At least 2 years
Testis At least 2 years
Thyroid At least 2 years
Breast At least 5 years
Colorectal At least 2 years
Prostate At least 2 years
Lymphoma At least 2 years
Skin : Melanoma At least 5 years
Squamous cell 2 years
Basal cell None

37.1.3 Severe cardiovascular disease e.g. diffuse disease on coronary angiogram, ejection fraction of < 35 %, valvular heart disease, ventricular arrythmia1 (Level C)

37.1.4 Diabetes mellitus with multiorgan failure

37.1.5 Psychiatric illness e.g. psychosis4

37.1.6 Noncompliance1,4 (Level C)

37.1.7 Active substance dependence or abuse e.g. alcohol,
amphetamines, cocaine, heroin4

37.1.8 Chronic active hepatitis or cirrhosis4,5 (Level C)

37.1.9 Age: > 55 years old. Patients between the age of 55 and 65 years of age are not at a significantly increased risk of post transplant morbidity as long as they do not have significant vascular disease.3 Consideration should be given on an individual basis.

37.1.10 Any disease with an expected survival of less than 5 years or with a resultant poor quality of life.

37.1.11 Primary renal disease.
Patients with end stage renal disease due to the following aetiology may be transplanted with caution:
a. Focal segmental glomerulosclerosis
b. Antiglomerular basement membrane (Anti GBM) disease. Transplant should be considered one year after end stage renal failure and the circulating anti GBM titre is no longer detectable in the blood. 2
c. Membranoproliferative glomerulonephritis type II (MPGN II).
d. Oxalosis. Patients can be treated with orthophosphate and pyridoxine, and preemptive renal transplantation with possible liver transplantation should be considered.6
e. Fabry’s disease

37.1.12 Secondary GN
a. Systemic Lupus Erythematosus (SLE).
Disease should be inactive for at least 6 months prior to transplant as assessed by clinical and serological status.
b. Haemolytic Uraemic Syndrome (HUS) or Thrombotic Thrombocytopaenia Purpura (TTP). Delay for at least 1 year prior to transplantation.
c. Idiopathic crescentic GN or Wegener’s or microscopic polyangiitis. Stable ANCA and asymptomatic for at least 6 months prior to transplantation.

37.2 Dialysis and nutritional status
37.2.1 Potential renal transplant recipients should be adequately dialysed to achieve good control of blood pressure, optimum status of hydration and acquire satisfactory nutritional status

37.2.2 Potential renal transplant recipients should have the following assessment :
a. Body weight
b. Body mass index
c. Triceps skin fold thickness
d. Mid arm circumference (MAC.)
e. Serum albumin
Patients on continuous ambulatory peritoneal dialysis (CAPD) may undergo renal transplant without Tenckhoff catheter removal prior to transplantation provided they are free from peritonitis or catheter related infection for at least 4 weeks.4 Similarly, haemodialysis patients may undergo renal transplant with an indwelling central venous dialysis catheter provided there is no evidence of catheter related infection.

37.3 Assessment of medical and psychiatric status
In women: breast and pelvic examination, Pap smear. In those over 40 years old or over 35 years old with a family history of breast carcinoma, mammography.6 In men: testicular and per rectal examinations

37.3.1 Assessment of the cardiovascular system
Full history and examination, CXR, ECG
Further assessment by cardiologist is indicated for the following cases:
a. male recipients who are more than 45 years old
b. female recipients who are 55 years old or premature menopause
c. recipients who are 35 years or older with coronary risk factors e.g. smoking, family history of coronary heart disease, diabetes mellitus, dyslipidaemia, obesity

37.3.2 Assessment of respiratory system
Full history and examination, CXR
Potential recipients with chronic smoking history and symptoms of chronic lung disease should be referred to a respiratory physician and anaesthetist for assessment

37.3.3 Assessment of the gastrointestinal system
Routine upper GI endoscopy should be performed in order to detect subclinical peptic ulcer disease (not routinely done in children unless symptomatic)

37.3.4 Urological evaluation
a. The following investigations should be routinely carried out in potential recipients
• KUB.
• Ultrasonography of kidneys / ureter.
• Micturating cystourethrogram (if there is a history of recurrent urinary tract infection, a suspicious renal tract abnormality or an unknown primary renal disease in a young patient).
b. For patients with suspected urological disorders, referral to urologist is required for further evaluation which may include a urodynamic study
c. The following group of potential recipients should be referred earlier to the transplant surgeon
• All diabetic patients
• Patients with a history of recurrent urinary tract infections
• Patients with raised PSA level
• Patients with adult polycystic kidney disease
• Patients with severe peripheral vascular disease

37.3.5 Assessment of pelvic vasculature
For selected patients e.g. past history of femoral catheterisation, long-term HD or increased iPTH, Doppler US studies, CT scan, MRA/angiogram when indicated

37.3.6 Assessment of the liver status
a. Routine assessment include ALT, HBsAg, HCVAb
• If HBsAg is positive, the patient should have HBeAg and HBV DNA tested.
• If HBsAg is negative and HBsAb is negative, the patient should be immunised with Hepatitis B vaccine (refer table 7.1)
b. Indications for liver biopsy4,8,9,10,11 (Level B)
• Patients with HCVAb or HCV PCR positive with or without elevation of liver enzymes
• Patients with positive HBsAg, negative HBeAg with or without raised liver enzymes

c. Following liver biopsy the patients should be treated as follows:
• If there is chronic active hepatitis (CAH), renal transplant is contraindicated.11,12 (Level C)
• If the liver enzymes is more than twice normal, renal transplant should be deferred until the enzyme has decreased to a level less than twice normal on 3 consecutive occasions separated by two weekly intervals between each reading. If there is chronic persistent hepatitis or milder disease with ALT less than 2X normal renal transplant may be carried out.13
d. Refer hepatologist for treatment of chronic hepatitis B and C
• Treatment of chronic hepatits B:
Treatment is indicated when HBsAg + > 6 months, HBeAg +, HBV DNA +, raised ALT (2X above upper limit), chronic hepatitis on biopsy. Treatment with either Interferon α-2b 5 million units daily or 10 million units 3X/ week for 3 to 6 months13,14,15 or Lamivudine 100 mg daily for at least 1 year.16,17,18
• Treatment of chronic hepatitis C:
Treatment is indicated when HCVAb +, HCV RNA +, raised ALT (2X above upper limit), chronic hepatitis (moderate to severe) on biopsy. Treatment is interferon α-2b 3 million units 3X per week for 6 to 12 months.19,20,21,22. Pegylated interferon 2a may be considered at a weekly dose of 135ug for 48 weeks with close monitoring for toxicity. 21

37.3.7 Assessment of the haematological system
Potential recipients should have haemoglobin of at least 8 g/dl before transplant. Blood transfusion for correction of anaemia is strongly discouraged. Patients should be treated with erythropoeitin after exclusion and treatment of underlying factors which contribute to anaemia

37.3.8 Psychological assessment 4
All potential recipients should be assessed psychologically with particular attention paid to the following areas:
a. Noncompliance with dialysis / medications
b. Alcohol and substance abuse (at least 6 months of documented abstinence)
c. Family support
d. Past psychiatric history / treatment
e. In children a full developmental assessment should be made
If indicated, a referral to a counselor or a psychiatrist should be made prior to further pretransplant evaluation.

37.3.9 Obesity
Attempts should be made for the potential recipients to achieve an ideal body weight (weight reduction should be carried out for potential recipient whose BMI> 30).

37.4 Dental evaluation
All potential recipients should be assessed by a dentist for dental clearance.

37.5 Management of pretransplant infection (1–2 weeks pre-transplant)
37.5.1 Screening for infection according to organ / system
a. ENT
Surveillance cultures should be taken from ear, nose and throat. Chronic suppurative otitis media should be excluded
b. Respiratory
CXR just prior to transplantation should be done
c. Genitourinary tract
Mid stream urine for C & S if potential recipient still having significant urine output
d. Miscellaneous
• CAPD catheter – dialysate for cell count and C & S and exit site swab for C & S if indicated
• Central venous catheter – exit site swab for C & S

37.5.2 Screening for specific infection
a. Tuberculosis (TB)
Any suspicion of active TB (radiological or clinical) should be thoroughly investigated and adequately treated. A six month period of observation after completing anti TB treatment is desirable before transplantation is undertaken
b. Toxoplasma
IgM antibody of > 1:4 is regarded as significant and the patient should be treated pretransplant
c. HCV
Screening is done by detecting HCV antibody
HCV antibody +ve patients can be considered for renal transplantation, subject to liver histology.24,25,26,27,28,29 Refer to figure 37.1 for details (Level C)
d. HIV
Screening by ELISA should be done twice during the pretransplant assessment. The first is done at the initial part of the assessment and the second preceding the transplant
e. HBV
Potential recipient who are HBeAg and HBV DNA positive in spite of treatment are excluded from transplantation
f. Cutaneous and genital warts should be treated pretransplant
g. Varicella Zoster Ab (refer to table 45.2)
h. Herpes Simplex Ab
i. Epstein Barr virus Ab
j. Cytomegalovirus (CMV)
IgG Ab against CMV is used for screening

37.6 Acute rejection prophylaxis
37.6.1 White cell cross match is done at the early stage of donor workup and one week prior to transplant (adapted from Guidelines for lymphocytotoxic cross match procedures, Renal Unit, Singapore General Hospital)

37.6.2 The following 6 cross matches should be performed by complement-dependent cytotoxicity (CDC) method:
a. T cell cross match (standard)
b. B cell cross match (standard)
c. Anti human globulin (AHG) enhanced T cell cross match
d. AHG enhanced B cell cross match
e. Dithiothreitol (DTT) treated T cell cross match
f. DTT treated B cell cross match

37.6.3 All T cell positive crossmatches i.e. presence of IgG or IgM anti HLA class I antibodies, contraindicate transplantation. IgG and especially IgM anti HLA class II antibodies indicate a less certain risk. T cell cross match detects anti HLA class I antibodies while B cell cross match detects both anti HLA class I and II antibodies. B cell cross matches are also more sensitive than T cell cross matches in identifying class I antibodies. AHG enhanced cross matches are more sensitive than the standard CDC (SCDC) method in detecting lymphocytotoxic antibodies, usually IgG. Conversion of a positive cross match to negative after pretreatment of recipient serum with DTT indicates the presence of IgM antibodies.

37.6.4 Many studies have confirmed that the historical crossmatch result is not relevant in sensitised recipients of a first transplant. The situation is less certain when the recipient of a historical positive, current negative crossmatch has become sensitised by loss of a first graft. Many centres would ignore a historical crossmatch result in first graft but not in regraft recipients.2,30 There remains considerable doubt about the degree of positive B lymphocyte crossmatch in influencing transplant outcome. Presence of autoantibodies in recipient sera can cause false positive crossmatch.30(Level C)



37.6.5 Panel Reactive Antibodies (PRAs)
PRAs are anti HLA antibodies against T & B cells from a panel of donors selected to represent the HLA specificities. The results are expressed as the % of panel cells that show positive antibody reactivity. Patients with PRA>20% should have enhanced immunosuppression. Serum screening determines:
a. Percentage of PRAs
Its value determines the likelihood of a negative cross match. Those with high % of PRAs are more likely to have a positive cross match and to be excluded from transplant. In international organ sharing algorithms, the PRAs value is used to increase queue points to improve patient’s chances of receiving a cadaveric transplant.
b. Anti HLA specificity of antibodies produced by the patient
A sequential record of antibody specificities over time can be used to avoid donors with those specificities and therefore diminish the likelihood of rejection episodes

References
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