Evaluation of kidney transplant candidates

Preparing for a transplant evaluation referral

Labs

• Must have a combined CKiD GFR <60 mL/min/1.73m²
• Get an ABO blood type if they have not had one prior

Imaging

• Get an echocardiogram if they have not had one prior
• If getting a kidney/bladder ultrasound, also have the radiologists assess the abdominal vessels for patency
  • Specify in the order details: “This is for a kidney transplant evaluation. Please assess aorta, IVC and iliac vessels for patency.”

Laboratory evaluation of candidates

• The exact laboratory evaluation that is performed varies by institution and patient history, but typically includes:
  • Blood type: ABO/Rh, completed on two separate samples

• Human leukocyte antigen (HLA)
• Chem 23: comprehensive metabolic panel (CMP), magnesium, phosphorus, triglycerides, total cholesterol, gamma-glutamyltransferase (GGT), total lactate dehydrogenase (LDH), uric acid, direct bilirubin
• Complete blood count (CBC) with differential
• Coagulation factors: prothrombin time (PT), partial thromboplastin time (PTT)/international normalized ratio (INR)
• Cystatin C
• Urinalysis
• Urine protein/creatinine ratio (UPCR)

Infection screening

• Hepatitis A virus (HAV): Anti-HAV antibody (IgG)
• Hepatitis B virus (HBV): [PDF: CDC interpretation guide]
  • HBcAb: hepatitis B core antibody (total, IgG + IgM),
  • HBsAb: hepatitis B surface antibody (quantitative and qualitative), and
  • HBsAg: hepatitis B surface antigen
• Hepatitis C virus (HCV): anti-HCV antibody (IgG)
  • If <18 months of age (maternal antibodies may persist), known infection, increased risk factors: also obtain quantitative HCV ribonucleic acid (RNA) nucleic acid amplification test (NAT or NAAT)
  • If <12 years of age, also obtain quantitative HCV RNA NAT prior to transplant (may be done as part of evaluation)

• Varicella-zoster virus (VZV) antibody (IgG and IgM)
• Cytomegalovirus (CMV) antibody (IgG and IgM)
• Epstein-Barr virus (EBV):
  • EBV nuclear antigen (NA) antibody (IgG),
  • EBV early antigen (EA) antibody (IgG), and
  • EBV viral capsid antigen (VCA) antibody (IgG and IgM)
• HIV-1 and HIV-2 immunoassay (ELISA)
  • If <18 months of age, maternal antibodies may persist: also obtain quantitative HIV 1 RNA PCR (viral load)
• Syphilis (Treponema pallidum): may use traditional or “reverse testing” algorithm, varies by institution
  • At Stanford Children’s, a chemiluminescent immunoassay (CLIA) is used as part of reverse testing algorithm
• Tuberculosis (TB): purified protein derivative (PPD) or interferon-gamma release assay (IGRA) [Redbook🔒]
  • PPD testing preferred if <2 years old
  • IGRA (e.g., QuantiFERON-TB Gold Plus or T-Spot) preferred if patient has received BCG vaccine or if unable to return for PPD check
• Toxoplasmosis: Toxoplasma antibody (IgG)
  • Recommended in all candidates by American Society of Transplantation (AST), though some centers will screen based on epidemiologic risk factors
  • Higher risk in Mexico as well as parts of Europe, Central and South America
• Titers (will re-immunize if serologies are negative/low):
  • Hepatitis B
    • If low (anti-HBs <10 IU mL), administer single dose and recheck; if still low, repeat entire series
  • Haemophilus influenzae type b (Hib)
    • Antibodies >0.15 mg/L confer protection
  • Measles, mumps, rubella
  • Pneumococcal
  • Varicella
    • While seronegativity is not as sensitive in vaccination-induced immunity (compared to that induced by wild type virus) and patients with varicella seronegativity may still have robust immune responses to VZV, the sensitivity is still quite good and there is correlation between antibody levels and varicella disease occurrence
    • Given the risk of severe varicella infection in transplant recipients, reimmunization of seronegative candidates is generally recommended prior to transplantation
      • Persistent seronegativity is an indication for postexposure prophylaxis

Infection screening based on epidemiologic risk factors (i.e., exposure):

• Inquire about all international travel as well as travel within the US in the past 2 years

Parasitic

• Strongyloidiasis: Strongyloides stercoralis antibody (IgG)
  • Serologic testing is more sensitive than stool ova & parasites
  • Tropics/subtropics: Central and South America, Africa, Southeast Asia, Western Pacific [map]
• Trypanosomiasis (Chagas disease): Trypanosoma cruzi (T. cruzi) serology
  • Parts of Mexico, Central and South America

Fungal

• Coccidioidomycosis (Valley fever, cocci): Coccidioides serology
  • California (esp. Central Valley and Central Coast), Utah, Nevada, Arizona, New Mexico, Texas, as well as parts of Mexico, Central and South America [CDC maps]
    • California: latest prevalence maps can be found in the Epidemiologic Summaries (final year-end reports) from CDPH
• Histoplasmosis: Histoplasma antibody (IgG)
  • Central/Eastern US (esp. Ohio and Mississippi River Valleys), as well as parts of Central and South America, Africa, Asia, and Australia [CDC maps]
  • Poor predictive value, so pretransplant screening is of limited utility.
    • American Society of Transplantation (AST) recommends against Histoplasma screening
    • Still important to consider histoplasmosis as a potential etiology when investigating post-transplant fever

Imaging evaluation

• Chest X-ray
• Electrocardiogram (ECG, EKG)
• Echocardiogram
• Abdominal ultrasound with doppler
• To evaluate anatomy and patency of iliacs, IVC and aorta
• MRA
• Consider in patients <20 kg, known vascular abnormalities, or ≤10 years old with congenital urologic abnormalities
• Use ferumoxytol (Feraheme®) for contrast (increased risk of nephrogenic systemic fibrosis with gadolinium-based contrast agents in patients with chronic kidney disease)

Multidisciplinary evaluation

• Nephrology
• Transplant surgery
• Urology (if indicated)
• Dietitian
• Pharmacy
• Social work
• Psychology
  • Typically for patients ≥6 years of age, but consider on a case-by-case basis for patients <6 years old
  • Also will evaluate caregivers
• Dental clearance
• Additional specialties as indicated

Specific considerations in evaluating candidacy

Chronic kidney disease

• Is etiology known?
  • Kidney biopsy? Review slides in-house if possible
  • Family history of kidney disease?
  • Genetic testing? Obtain report if possible
• Current estimated GFR:
  • Must be <60 mL/min/1.73m² to be listed
  • Consistently <20 mL/min/1.73m² before being activated for transplant
• If on
  hemodialysis (HD)
  or
  peritoneal dialysis (PD)
  , note date of initiation and obtain copy of form CMS 2728
  • Must consider the need for dialysis prior to transplant and the potential impact on timing of admission/transplant
  • Patients will get credit for time on the waitlist from the first day of starting dialysis, but documentation is required

• Polyuria or oliguria?
• If possible, quantify by measuring 24-hour urine output

Cardiovascular/hypertension

• Is blood pressure well controlled?
• Number of antihypertensive medications?
• 24-hour ABPM done?
  • Recommend in patients on dialysis or those with known hypertension
• Assess for left ventricular hypertrophy (LVH) on echocardiogram
• Cardiac function normal?
  • If not, consult cardiology for consideration of cardiac cath

Pulmonary

• History of pulmonary hypoplasia?

History of steroid exposure

• Length of steroid use?
• Last dose of steroids?
• Known side effects/complications from steroid use?

Autoimmune disease

• Serologies?
• Maintenance immunosuppression?
• Date of last flare?
• If patient has autoimmune disease, consult rheumatology for transplant clearance

Urology

• Any congenital anomalies of the kidneys or urinary tract (CAKUT)?
• Kidney and bladder ultrasound normal?
• History of neurogenic bladder or dysfunctional voiding?
• History of kidney stones?
• Any urinary tract infection (UTI) history?
  • Frequency of prior UTIs
  • Date and severity (e.g., simple cystitis, pyelonephritis, cyst infection) of most recent UTI
  • Is circumcision indicated at time of transplant?
• Presence of vesicostomy?
  • Plan for takedown before or after transplant?
• If any of the above, consider urology consult

Gastrointestinal (GI)

• Feeding intolerance?
• Feeding tube in place?
• Oral aversion?
  • Able to tolerate any PO meds?

Endocrine

• Diabetes in patient/family?
• Discuss increased risk of diabetes with tacrolimus, steroids

Hematologic

• Hypercoagulability?
• Increased risk in infants, nephrotic syndrome

History of malignancy

• How long has the patient been cancer free?
• Consult cardiology for transplant clearance

Infectious disease

• Are immunizations up to date?
  • If not, will need to have a catch-up plan. Should be caught up with inactivated vaccines at least 2 weeks prior and live vaccines at least 4 weeks prior to transplant.
• For patients on
  PD
  : history of peritonitis or PD catheter site infection?
• For patients on
  HD
  : history of HD catheter site infection?
• Note CMV, EBV IgG status
• Review titers (varicella, Hib, MMR, pneumococcal) and reimmunize if negative
• Ensure family is up to date on immunizations, particularly varicella and pertussis

Tuberculosis (TB)

• Review history of exposure to TB and details of prior TB testing results
  • Inquire about family members’ history of active/latent TB and prior treatments
  • Active disease should be treated aggressively
• Latent tuberculosis infection (TBI, LTBI) should also be treated [Redbook🔒]
• Treatment does not need to delay transplant; can start immediately and continue after transplant with increased surveillance for active disease

Zoonotic exposures

• Pets, farm animals, visits to petting zoos
• Recent insect bites (ticks, mosquitoes)
• If sexually active, consider testing for gonorrhea and chlamydia

Dietary exposures

• High risk foods
• Unpasteurized dairy (raw milk)

Neurologic

• History of seizures?
  • Discuss increase risk of seizures with tacrolimus

Sensitization risks

• History of sensitizing events: blood transfusions, repeat transplant, pregnancy
• Panel reactive antibody (PRA)?
• Does the patient require desensitization or plasmapheresis at time of transplant?

Vascular

• Did the patient require umbilical lines (UAC/UVC) as a neonate?
• Location(s) of previous central/PICC lines
• Do the relevant vessels remain patent on imaging?

Psychosocial considerations

• Family understanding of potential benefits as well as the burdens that transplant will place on the family
• Does the patient have a primary care physician (PCP)?
  • Are they comfortable with managing primary care for this patient post-transplant?

Immunosuppression plan

• Induction immunosuppression?
• Maintenance immunosuppression: steroid free or steroid based?

Nephrectomy

Patients may need to have one or both of their native kidneys removed at time of transplant:

• Uncontrolled kidney-related hypertension
• Difficult to control kidney-related hypertension
• Polycystic kidney disease, especially in patients with a history of infected cysts or very large kidneys
• Polyuria to a degree that the recipient would have difficulty keeping up enough fluid intake to balance the urine lost from the transplanted kidney and native kidneys
• Severe vesicoureteral reflux and megaureter that is not amenable to repair
• Recent history of recurrent UTIs
• Need for space

Immunization requirements

• Patients are typically required to receive all medically indicated immunizations prior to transplant
  • Transplant candidates are expected to continue to receive all medically indication immunizations after transplant

Timing of immunizations

• If necessary, catch-up immunizations should be started immediately upon referral
• Before transplant:
  • To ensure adequate immune response, inactivated vaccines should be given at least 2 weeks prior to transplant
  • To ensure viral replication has ceased prior to transplant, live-attenuated vaccines should be given at least 4 weeks prior to transplant
• Antibody-containing blood products:
  • Certain live virus vaccines (specifically MMR and varicella) can have diminished immune responses due to antibodies contained in blood products
  • Examples of antibody-containing blood products include: RBCs (excluding washed), platelets, plasma products, IVIG, infection-specific immune globulins, RSV antibody (Synagis [MedImmune])
  • If a patient receives antibody-containing blood products <14 days following MMR or varicella vaccine, vaccine should be repeated after the recommended interval unless serologic testing indicates a protective antibody response
  • For a patient who received antibody-containing blood products, MMR or varicella vaccines should be delayed by the recommended interval (≥3 months depending on the blood product and dose; see Table 3-6)
    • If that is not possible (e.g., patient is receiving regular IVIG infusions), try to time vaccine administration at least 14 days prior to next dose of antibody-containing blood products.
      • Note that the patient is unlikely to have an optimal immune response given the continued presence of passively acquired antibody.
      • If not contraindicated, vaccination should be repeated after the recommended interval (e.g., if therapy is discontinued)

Notes on specific immunizations

• Influenza [immunize.org]
  • All transplant candidates and listed patients >6 months old should receive annual vaccination
• Pneumococcal [immunize.org]
  • PCV13 (Prevnar 13)
    • 13-valent pneumococcal conjugate vaccine protects against 13 capsular serotypes (~90% of invasive disease in children)
      • Produces memory B-cells by eliciting T cell immunity, reducing bacterial carriage in the respiratory tract
    • More effective than PPSV23 in children <2 years old
  • PPSV23 (Pneumovax 23)
    • 23-valent pneumococcal polysaccharide vaccine contains capsular polysaccharides from 23 common serotypes of S. pneumoniae
      • Produces a T-cell independent immune response; does not reduce bacterial carriage
• Measles, Mumps, Rubella (MMR)
  • If solid organ transplant is impending, it is acceptable to give MMR as early as 6 months of age
    • Note that doses administered prior to 12 months of age do not count toward the 2-dose primary series
  • See above regarding wait times around administration of blood product and derivatives

Close contacts

• It is strongly recommended that all close contacts (i.e., household members) be fully immunized prior to transplant
  • Varicella and pertussis immunizations are particularly important to remind families about
  • Annual influenza immunization is also recommended (inactivated virus is preferable)
• No live vaccinations are contraindicated, but precautions should be taken in the following circumstances:
  • Live-attenuated influenza vaccine (LAIV): maintain good hand hygiene for 2 weeks after the vaccine is given
  • Varicella (chickenpox)/herpes zoster (shingles): if skin lesions develop after getting the vaccine, avoid contact with the transplant recipient until the lesions have resolved
    • Note: for Zostavax (Merck); this precaution does not apply to Shingrix (GSK), which is a recombinant protein zoster vaccine
  • Rotavirus: transplant recipients should practice good hand hygiene and avoid handling diapers of recently-vaccinated infants for 4 weeks after vaccination
  • Measles, mumps, rubella (MMR): mother-to-infant transmission of rubella via breastmilk has been reported

Patient approval

After a full transplant evaluation is completed, the patient is presented at the multidisciplinary transplant selection meeting.

Criteria for candidacy

• Pediatric patients up to age 18 who have end stage kidney disease (ESKD) or are approaching ESKD.
  • Older patients (18-21 years) with ESKD are typically referred to adult nephrology for transplant evaluation, but may be considered in certain circumstances (e.g., complicated urologic issues, psychosocial/developmental issues).
  • Patients with intra-abdominal vascular compromise or thrombosis are typically considered as candidates only for pediatric (or very small adult) deceased donors.

Contraindications to candidacy

• Uncorrectable psychological instability that would interfere with treatment adherence
• Active malignancy
  • Can be listed inactive, but will not be activated for transplant until in remission for 2 years
• Sepsis
• Severe active viral disease

UNOS Listing

• For dialysis dependent patients, their waiting time starts with the first date of dialysis (i.e., when listed for transplant, dialysis patients retroactively get “credit” for time on the transplant list from the day they started chronic dialysis)
• For non-dialysis dependent patients who are accepted because of low GFR and/or uremic symptoms, their waiting time starts on the day they are accepted onto the waiting list

Active/inactive

• There are two “statuses” on the transplant wait list: active and inactive
• A patient’s status can be changed between active/inactive status if their clinical status changes
• Patients accrue time on the waiting list regardless of whether their status is active or inactive
• Active listing: eligible to receive offers from deceased donors
  • Patients are listed as active if the multidisciplinary committee determines they require a kidney transplant and are ready to receive a transplant at any time
• Inactive listing: not eligible to receive offers from deceased donors
  • Patients may be listed as inactive if the committee determines they will eventually require a kidney transplant but they are currently too sick to receive a transplant or if they are still well enough that they do not require a transplant immediately