Download Proposed PMB guide torenal transplant listing

Proposed PMB guide
to renal transplant listing
For SATS controversies meeting
7 May 2011
Background
• Transplantation currently optimum available form
of renal replacement therapy
• In ideal case
– Improved survival
– Improved QoL
– Cheaper
• Above not universally true for all on dialysis
– May not improve survival or may lead to loss of life
– May worsen QoL
– May not more expensive
Roles of discriminant criteria
• Exclude patients who will not benefit from
treatment
– Will have poorer survival outcome
– Qol unlikely to improve or likely to worsen
– These are medical contraindications
• Ration care to those most likely to optimise use
of a scarce resource
• Inclusion criteria –pick the best only
• Often not purely medical
• Rationing of care
Ideal candidate
•
•
•
•
•
•
•
•
•
•
Young 25-45yrs old
Non diabetic
Known cause of renal disease with no risk of recurrence
Little or no time on dialysis
No cardiac or other disease
No chronic infection
Not pre sensitized
Well educated
Has an identical twin
Is rich and grateful!
Medical contraindications
• Risk of transplant > benefit
– Survival
– Decreased QOL or morbidity
– Poor likely graft survival
•
•
•
•
•
•
•
Active infection
Active malignancy
Severe Cardiovascular disease
Other severe major organ failure
Active Psychiatric disease including substance abuse
High risk of recurrent native kidney disease
Structural problems precluding transplantation
– Bladder dysfunction
• Other
Rationing
•
•
Patients known to have poorer outcomes than others
These would still do better with transplant compared to dialysis but have poorer
than ‘ideal’ outcomes.
–
–
–
–
–
–
–
–
–
–
–
•
Diabetics
Moderate risk of recurrent disease or gradual recurrence
Morbidly Obese
Smokers
HIV positive
Hepatitis B/C
Adolescents
Elderly
Presensitized
Repeat transplants
Previous cancer
Where do you draw the line?
Age
• No age cutoffs
• Several studies show transplant better than
dialysis even in patients over 70 years old
–
Benefit of kidney transplantation beyond 70 years of age.Heldal K, Hartmann A, Grootendorst DC, et al.Nephrol Dial Transplant. 2010
May;25(5):1680-7.
• Complete history and physical exam to assess
suitability
• Emphasis on cardiac health
• Screen for common cancers
• May be candidate for ECD kidney
• Discuss with patient
Active infection
• Intuitive – dangerous to further suppress immunity in patient with active
infection
• HIV – evidence pre -ARV era suggests disastrous outcome
• Must be–
–
–
–
–
stable on ARVs
suppressed VL/CD4 > 200
Adherence
No AIDS defining illness post immune reconstitution
Ongoing available ARV options
• Higher risk of ACR
• More complicated but possibly cheaper?
• Hepatitis B – risk of progression
– Exclude cirrhotics ( may do Liver + kidney)
– Exclude active replicators – pre-treat
– Prophylactic therapy for carriers
Active infection
• Hepatitis C
– Similar to Hep B
– Treatment more problematic
– No prophylaxis
– Controversial area but not an absolute
contraindication in literature
Hep C algorithm
Morales and Campistol, J Am Soc
Nephrol 11: 1343–1353, 2000
Active infections
• HPV
– Treat pre-malignant lesions
– Vaccinate
• Other
– TB –treat
– Genital Herpes –prophylaxis
– Treat diabetic foot ulcers
• In general if infection not treatable or
controllable not for transplant
Malignancy
• Screening for common cancers
–
–
–
–
–
–
Mammogram
Pap smear
PSA/DRE
CXR
PHYSICAL EXAM
Further guided by individual risk eg
• Family history
• Analgesic nephropathy
• Previous cyclophosphamide
Malignancy
• Cured malignancy may be transplanted after a waiting
period.
• Criteria defining cure - oncology
• The issue of recurrence was addressed in a retrospective
study of 1297 renal allograft recipients with a history of
malignancy .
– tumors diagnosed before transplantation- frequency of
recurrence after transplantation was 21%.
– For tumors diagnosed after transplantation the respective figure
was 33%.
– Among tumors diagnosed and treated before transplantation,
the frequency of recurrence after transplantation was highest
for breast cancer, symptomatic renal cell cancer, sarcoma,
bladder cancer, and multiple myeloma
Penn I: Evaluation of transplant candidates with preexisting malignancies. Ann Transplant 2: 14–17, 1997
Recommended Wait Time (Years) Based on Type of
Cancer Before Listing for Transplantation
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Type of Cancer
Breast cancer
Colorectal cancer
Melanoma
Uterine cervical cancer
Renal cell carcinoma/Wilm's tumor
5 cm)
Bladder cancer
Kaposi sarcoma
Leukemia
Lung cancer
Lymphoma
Prostate cancer
Testicular cancer
Thyroid cancer
Skin (nonmelanoma) cancer
Liver cancer
Myeloma
Recommendation (years)
> 5 (> 2 for early disease)
> 5 (> 2 for Dukes Stage A or B1)
> 5 (> 2 melanoma in situ)
> 2 (> 5 for more advanced cervical cancer)
> 2 (> 5 for large cancers; no wait for incidental tumor <
>2
>2
> 2 (limited data to make recommendation)
>2
> 2 (possibly > 5)
> 2 ( possibly less for localized disease)
>2
>2
0-2 (no wait for basal cell carcinoma)
Unable to give recommendation
Unable to give recommendation
Kasiske BL, Cangro CB, Hariharan S, et al. The evaluation of
renal transplant candidates: clinical practice guidelines.
Recommendations for outpatient surveillance of renal
transplantation. Am J Transplant. 2001;suppl 2:5-95.
Cardiovascular disease
• Peri-operative risk
– Death
– Perioperative morbidity
• Post transplant –accelerated vascular disease
• Need to risk stratify and investigate appropriate
patients
• Can the condition be improved?
– Coronary revascularization
– Treatment of other reversible factors
• Can the transplant surgery be done –technically?
Cardiovascular disease
• Manske et al -151 diabetic candidates for
transplant angiography, 31 had stenotic
lesions >75% without typical pain and EF>35%
• 26 agreed to be randomized
– Medical (aspirin and CCB)
– Intervention (angioplasty or CABG)
• Over median 8,4 months 10/13 medical vs
2/13 revasc hads CVS endpoint
Cardiovascular disease
• In 2001 AST recommended
– High risk patients with DM or >2 risk factor should
have stress test
– If stress positive do angiography
– Patients with critical lesions should be
revascularized
– Practiced widely
Cardiovascular disease
• More recent Coronary artery revascularization
prophylaxis (CARP) trial
• Pre major non cardiac vascular surgery (not
transplant population) found no difference
between medical and interventional approaches
• ACC/AHA do not recommend routine screening
without symptoms for non-cardiac surgery (not
transplant patients)
• Even more recently Aalten et al found no
additional benefit to standardized screening for
asymptomatic patients as recommended
Jeroen Aalten, Stijn A. Peeters, Maureen J. van der Vlugt, and
Andries J. HoitsmaIs standardized cardiac assessment of
asymptomatic high-risk renal transplant candidates
beneficial?Nephrol. Dial. Transplant. (2011) first published online
February 14, 2011
CVS risk
• Carotid plaque is associated with increase risk of
ischaemic heart disease and stroke.
• Older Age and diabetes are associated with
increased risk
• Length of time on dialysis is associated with
increased risk of cardiac death post transplant
• Post transplant factors have immense weight on
cardiovascular outcome
• Traditional risk factors tend to underestimate risk
Cardiovascular disease
•
Kumar et al (2009) – pre –dialysis angio for transplant workup is safe (avg GFR 12)
–
•
Lorenz et al-similar results in 2010 study
–
•
•
•
•
Effect of Elective Coronary Angiography on Glomerular Filtration Rate in Patients with Advanced Chronic Kidney Disease,” CJASN December
2009 vol. 4 no. 12 1907-1913
Lorenz, E. et al (2011), The effect of coronary angiography on renal function in preemptive renal transplant candidates. Clinical
Transplantation, 25:
Silent Coronary artery disease common in Diabetics (esp older) in general
population
Several observational studies have found stress ECG, Perfusion scanning and other
non-invasive test to have low sensitivities
Varying recommendations for surveillance of patients on list
KDOQI
–
–
–
Similar to AST
No routine stress testing or angiography
Surveillance on wait list
KDOQI guidelines
•
•
•
•
•
•
•
•
•
•
•
•
•
2.1 The evaluation of CAD in dialysis patients depends on individual patient status. (C)
2.1a If the patient is on the kidney transplant waitlist and is diabetic (and initial evaluation is negative for CAD), then evaluation for CAD
every 12 months is recommended.
2.1b If the patient is on the transplant waitlist but is not diabetic and is classified as “high risk,” then evaluation for CAD every 24
months is recommended.
*2.1c If the patient is on the transplant waitlist and is classified as not high risk, then evaluation for CAD every 36 months is
recommended.
*2.1d If the patient is on the transplant waitlist with known CAD (and not revascularized), evaluation for CAD should be performed
every 12 months.
2.1e If the patient is on the transplant waitlist and has a history of PTCA or coronary stent, evaluation for CAD should be performed
every 12 months.
2.1f If the patient has “complete” coronary revascularization (i.e., all ischemic coronary vascular beds are bypassed), the first reevaluation for CAD should be performed 3 years after coronary artery bypass (CAB) surgery, then every 12 months thereafter.
2.1g If the patient has “incomplete” coronary revascularization after CAB surgery (i.e., not all ischemic coronary beds are
revascularized), then evaluation for CAD should be performed annually.
2.1h If there is a change in symptoms related to IHD or clinical status (e.g., recurrent hypotension, CHF unresponsive to dry weight
changes, or inability to achieve dry weight because of hypotension), evaluation for CAD is recommended.
2.1i Dialysis patients with significant reduction in LV systolic function (EF<40%) should be evaluated for CAD
.2.1j Evaluation for heart disease should occur at initiation of dialysis and include a baseline electrocardiogram (ECG) and
echocardiogram (see Cardiomyopathy guideline for echocardiography after dialysis initiation). Both of these tests provide information
pertinent to, but not restricted to, CAD evaluation. Annual ECGs are recommended after dialysis initiation.
2.2 In patients fulfilling 2.1.a-2.1.i above, CAD evaluation should also include exercise or pharmacological stress echocardiographic or
nuclear imaging tests. “Automatic” CAD evaluation with stress imaging is currently not recommended for all dialysis patients (i.e.,
patients not fulfilling 2.1.a-2.1.i). Stress imaging is appropriate (at the discretion of the patient’s physician) in selected high-risk dialysis
patients for risk stratification even in patients who are not renal transplant candidates. (C)
2.3 Patients who are candidates for coronary interventions and have stress tests that are positive for ischemia should be referred for
consideration of angiographic assessment. (C)
Non invasive testing
• Physical stress often not possible to achieve adequate
target HR
• Perfusion scans with pharmacologic stress often done
• Sensitivity varies in studies 37-90%
• Specificity varies 40-90%
• Positive test correlates with six fold risk of death.
• In high risk cases more useful if positive, may be less
useful if negative
• Dobutamine stress echo gaining popularity but also
imperfect
Angiography
• Invasive
• Costly
• Not clear benefit even with revascularization
in view of better medical management
• Not clear what best approach is
– Bare stent
– Drug eluting stent
– CABG
Evaluation
•
•
•
•
•
•
No widely accepted standard recommendations
Most practice cardiac evaluation of “HIGH-RISK’ candidates
Evaluation strategies generally hinge around initial non-invasive testing .
All symptomatic patients ,known CAD pts or patients with low EF should have
testing and probable angiography
Angiography recommended by some guidelines for Asymptomatic Diabetics due to
poor negative predictive value of non-invasive testing in high risk patients and high
incidence of silent disease (especially in older) but not evidence based
Asymptomatic Diabetics with following criteria at low risk (may not need further
testing)
–
–
–
–
•
•
<45 yrs old
IDDM <25 yrs
<5pk yrs smoking history
Normal ecg
LV systolic dysfunction(<40%) poor prognosis but some studies have documented
improval in some cases
Not clear what best revascularization approach is
Other vascular disease
• Patients with severe CVA may have poor
rehabilitative potential
• Anti –seizure and other meds that interact
with transplant drugs should be modified if
possible pre transplant to avoid problems
• Peripheral vascular disease if severe may
preclude transplant technically and have
poorer post op survival
Other organ failure
• Limits peri operative survival if severe
– All patients should have CXR in addition to full
clinical assessment for pulmonary disease
– Adequate pulmonology assessment including
lung function testing in symptomatic patients
– Patients with suppurative lung diseases precluded
• Liver disease
– Liver kidney transplant may be appropriate for
selected patients with cirrhoses
Git disease
• H pylorii should be treated if found but
routine screening not done in all centres
• Patients with history of diverticular disease
should have assessment by barium study or
scope and may require surgery if very
extensive
• Colonoscopy in patients over 50 or those with
risks for cancer
Psychiatric disease
• Untreated substance abuse a contraindication
• Active psychosis/BMD/Depression a contraindication
• Stress around transplant procedure may precipitate
worsening of condition
• Transplant drugs may be neurotoxic
• All patients need detailed psychosocial assessment before
wait listing –with psychiatric referral if appropriate
• Assessment of cognitive function should be included
• Education is a key aspect of care to prevent peritransplant
psychosocial morbidity
• Treated patients with low risk of relapse may be listed.
• Some psychotic conditions not transplantable
Smoking
• Higher risk of cardiovascular disease and death in
recipients
• Higher risk of graft loss in some studies
• Only observational data
• No good data comparing to wait listed but not
transplanted smokers
• Some centres exclude patients not willing to quit
• Evidence of lung disease or severe cardiovascular
disease with ongoing smoking should preclude
transplant
Obesity
• Higher risk of peri-operative complications in morbidly
obese patient including wound infection
• Higher risk of DGF
• Higher risk of NODAT and cardiovascular disease
• Weight gain common post transplant
• Many use BMI >35% as cutoff although no specific data
support this figure, relationship likely to be linear
• Several studies demonstrate comparable graft and
patient survival even in morbidly obese patients
Urology
• Ideally
– Sterile
– Continent with no outflow obstruction
– Normal neurological function and compliance
• VCU is useful to diagnose asymptomatic problems in patient who
pass little urine (patients with good RRF can be screened for post
mic residual)
• Recent sonar (<2-3 yrs old should be available)
• Patients with a history of urologic disease and patients younger
than 20 should have full assessment including VCU, cystoscopy and
UDS with appropriate urological intervention where needed
• PSA and DRE should be done in all males over 40 and repeated
annually
Recurrent disease
• FSGS – 20-40% recurrence rate
– Younger, rapid onset, previous recurrence
– Exclude living donor if previous recurrence?
• IgAN –frequent recurrence but uncommon or
slow graft loss
• Congenital TTP
• Active SLE (should require minimal therapy)
• Active ANCA assoc vasculitis
• Primary oxalosis- must get liver also
Adherence to therapy
•
•
•
•
•
History of non-adherence
Poor support
Neurological/psychiatric issues
Drug interactions and complexity of regimen
Financial issues
Other
• Hyperparathyroidism- may need surgical
treatment in some
• Identify thrombophilic patients
• Identify highly sensitized patients
Suggested approach
• Patient should have need for chronic RRT
– On chronic dialysis
– GFR 18-20 and declining with anticipation of dialysis within 6-12 months
• Where possible cause of ESRD should be ascertained
• Educate patient and family as to risks and benefit of procedure ,assess
patients willingness to be transplanted
• Full clinical evaluation – look for obvious exclusions (eg other organ
failure)
• Lab tests
– FBC ,U&E, LFT ,CMP, HIV, Hepatitis studies, CMV, WR, PTH, glucose,
cholesterol, PI/PTT
– Other in individual patients eg ANCA ,ANF, PSA, CD4,CRP,ESR
– Urine MC&S and protein estimation
– Pap smear in women
Suggested approach
•
•
•
•
•
CXR
Mammogram in women >40 yrs old
Sonar (if not already available)
VCU (and further urology as discussed)
Cardiac evaluation as per risk stratification (at least ECG
and Echo in all)
• Psychosocial evaluation
– Psychology/psychiatry
– Social worker
• GIT evaluation where needed (all patients should be on
PPI post transplant)
Suggested approach
• Dental assessment –electively treat problems
and to rule out periodontal or oral infections
• Screen for sensitization with PRA
• Crossmatch CDC and Flow cytometric pre
transplant ( done before full workup of donor
in case of living donor)
Process of listing
• Must have multidisciplinary transplant evaluation committee with
standardised process.
• Guidelines will never cover every eventuality
• In general patient can be listed if
– Transplant would be better than dialysis for this patient
– Patient likely to survive at least 5 years (even on dialysis)
– Even with above rationing may be practiced if wait time ‘astronomical’
eg 10 yrs
• Decisions should be consistent –so wise to keep detailed minutes
• Useful to have tick lists
• Patients who initially fail may be re-presented if more data available
or reversible condition treated