Proposed PMB guideto renal transplant listing

For SATS controversies meeting7 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 pre-existing malignancies. Ann Transplant 2: 14–17, 1997

Recommended Wait Time (Years) Based on Type of Cancer Before Listing for Transplantation

• Type of Cancer Recommendation (years)• Breast cancer > 5 (> 2 for early disease)• Colorectal cancer > 5 (> 2 for Dukes Stage A or B1)• Melanoma > 5 (> 2 melanoma in situ)• Uterine cervical cancer > 2 (> 5 for more advanced cervical cancer)• Renal cell carcinoma/Wilm's tumor > 2 (> 5 for large cancers; no wait for incidental tumor < 5 cm)• Bladder cancer > 2• Kaposi sarcoma > 2• Leukemia > 2 (limited data to make recommendation)• Lung cancer > 2• Lymphoma > 2 (possibly > 5)• Prostate cancer > 2 ( possibly less for localized disease)• Testicular cancer > 2• Thyroid cancer > 2• Skin (nonmelanoma) cancer 0-2 (no wait for basal cell carcinoma)• Liver cancer Unable to give recommendation• Myeloma Unable to give recommendationKasiske 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)

– 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 et al-similar results in 2010 study– 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 recommen

ded.• *2.1d If the patient is on the transplant waitlist with known CAD (and not revascularized), evaluation for CAD should be performed ever

y 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 eve

ry 12 months.• 2.1f If the patient has “complete” coronary revascularization (i.e., all ischemic coronary vascular beds are bypassed), the first re-evaluati

on 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 chan

ges, 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 echocardiogra

m (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