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Dr David McGregorClinical Director/Nephrologist
Christchurch Hospital
Christchurch
11:00 - 11:30 Renal Transplantation Basics
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Kidney Transplantation
Dr David McGregor
Department of Nephrology
Christchurch Hospital
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Overview
• ESKD
• Why transplant?
• Transplant workup
• Transplant procedure
• Complications post transplant
• Kidney Donation
• How can general practice help ?
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End stage kidney disease (ESKD)
• Permanent failure of the kidneys, such that a person would die without treatment
• eGFR < 15 ml/min (normal = 100)
• Usually symptomatic
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More patients with treated ESKD each year
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Starting treatment in New ZealandPatients 65 to 84 years have highest incidence of treatment (and diabetes is most common cause)
2010 16
13
14
63
8574 77
86
254 253
222
227
215
324
364
406
311
345
216224
274260
293
1455
39
0
61
0
50
100
150
200
250
300
350
400
450
2012 2013 2014 2015 2016
Inci
den
ce, p
er m
illi
on
po
pu
lati
on
0-24
25-44
45-64
65-74
75-84
85+
0 10 20 30 40 50 60
GN
Analgesic
Polycystic
Reflux
Hypertension
Diabetes
Other
Uncertain
Not reported
Percentage of patients starting RRT
New Zealand
Australia
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Treatment Options
• Haemodialysis
• Peritoneal Dialysis
• Kidney Transplant
• Supportive Care (= Palliative Care)
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Benefits of kidney transplantation
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1-Quality of Life much better with transplant
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ESKD symptoms
• Malaise, lethargy
• Anorexia, weight loss
• Restless legs, cramps, itch
• Fluid overload, pulmonary oedema
• Loss of libido, infertility
• All improve or resolve with transplant
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Complications of ESKD
• Anaemia
• Bone disease – PTH, osteomalacia
• Abnormal calcifications
• Accelerated atherosclerosis
• Depression, inability to work
• Most improved with transplant
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2 - Survival is better with a transplant
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13
Fully adjusted HR for death 0.27 (0.11-0.64)
*age, ethnicity, gender, presence and type of DM, co-morbidity, treating hospital, primary renal disease, BMI, eGFR at RRT inception, smoking, late referral for RRT
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3 –Transplants less expensive
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Kidney transplantation
• The treatment of choice for almost all patients with ESKD• Quality of life
• Quantity of life
• Cost
• So what proportion of incident NZ ESKD patients are transplanted?
•About 5%
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Starting treatment in New ZealandMost patients start treatment with dialysis (and haemodialysis)
0
10
20
30
40
50
60
70
80
90
Haemodialysis
Peritoneal dialysis
Transplant
New patients, modality per million
0
100
200
300
400
500
600
Transplant Dialysis
533 people started with dialysis and
26 had a preemptive transplant
Relative to population growth, PD
appears to be increasing, HD
decreasing, and (so far) transplant
unchanged
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0
5,000
10,000
15,000
0
1,000
2,000
3,000
1990
19
91
1992
1993
19
94
1995
19
96
1997
1998
1999
2000
20
01
2002
2003
20
04
2005
20
06
1990
1991
1992
1993
19
94
1995
1996
19
97
1998
19
99
2000
2001
20
02
2003
20
04
2005
2006
Australia New Zealand
Dialysis Graft
Nu
mb
er
Prevalent ESKD Patients
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Prevalence of renal replacement therapy in New ZealandTransplant prevalence growing faster than population, however different by ethnicity
561587 594
582 580
345 355 359 369 376
0
100
200
300
400
500
600
700
2012 2013 2014 2015 2016
Nu
mb
er o
f p
ati
ents
, pm
p
Dialysis
Transplantation
0
20
40
60
80
100
120
140
160
180
2012 2013 2014 2015 2016
Tran
spla
nts
per
10
0 d
ialy
sis
pat
ien
ts
Pacific men
Pacific women
Maori men
Maori women
NZ European men
NZ European women
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Why not transplant everyone with ESKD ?
• Older sicker patients may not benefit
• Unable to find suitable match
• Lack of engagement with transplant process
• Contraindications• Bad vascular disease (Diabetics)
• Cancer or chronic infection
• Risk of recurrent kidney disease
• Poor adherence with medication
• More ESKD patients than kidneys available
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Overview
• ESKD
• Why transplant?
• Transplant workup
• Transplant procedure
• Complications post transplant
• Kidney Donation
• How can general practice help ?
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Transplantation is a team sport
• Nephrologists, dialysis staff
• Transplant surgeons (vascular surgeons)
• Donor surgeons (urologists), Radiologists
• Transplant Coordinators
• NZ Blood service
• Donor counsellor, Psychologist
• South Island Transplant committee
• Retrieval team
• Nurses, anaesthetists, pharmacist
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Recipient Workup
• Suitable patient identified by nephrologist
• Education – transplant and dialysis
• Medical tests• Viral serology and vaccinations (VZV, HBV)• Stress echocardiogram• Dental check• Cancer check – skin, breast, cervix, prostate• Surgical assessment
• Committee decision • DD list - Central NZ-wide list, monthly bloods• Living donor only - less stringent criteria
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Deceased donor kidney waiting list and allocation
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Deceased donor list eligibility
* Can be listed before dialysis but no waiting point accrual until on dialysis# DD list only – LRD still possible of donor available
*
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Why restrict eligibility?
• Utility vs equity considerations
• Kidneys in short supply
• Aim to gain most benefit from scarce resource
• Not solely based on age but predicted survival
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Allocation
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Overview
• ESKD
• Why transplant?
• Transplant workup
• Transplant procedure
• Complications post transplant
• Kidney Donation
• How can general practice help ?
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Transplant procedure (DD)
• Donor identified (ICU)
• Central coordination (ODNZ)
• Recipient selection• ABO compatibility
• HLA (tissue) typing
• Waiting time
• Cross match negative (monthly bloods)
• Nephrologist called
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Transplantation process (DD)
• 3 transplant units – Auckland, Wellington, Christchurch
• Nephrologist:• Confirms recipient suitability
• Contacts recipient • ?well ?avail ?want this kidney ?dialysis
• Contacts surgeon
• Contacts ward
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Post transplant care
• Usually discharge day 5-7
• Daily OP visits for first month
• Then reducing frequency
• After 1 year reviewed 3-6 monthly
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Immunosuppression
• Immunosuppression prevents rejection
• Used in combination for as long as kidney is working• Prednisone
• Mycophenolate (Cellcept)
• Cyclosporine (Neoral) or Tacrolimus (Prograf)
• Many interactions (foods, other drugs)
• Adherance vital• Timing
• Not skipping
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Prednisone
• Dose dependent
• Worse early
• Progressive dose reduction
• Patients hate SE’s but stopping = risk of rejection
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Immunosuppresion side effects
• Mycophenolate• Nausea and diarrhoea
• Bone marrow suppression (monitor FBC)
• Cyclosporine• Hypertension
• Toxic to kidneys (monitor)
• Facial/ body hair
• Gum hypertrophy
• Tacrolimus• Diabetes – may require insulin
• Thinning hair
• Toxic to kidneys
• Neurotoxicity
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Other medicines after transplant
• Iron
• Omeprazole
• Sulphamethoxazxole/Trimethoprim• To prevent PCP lung infection
• Valganciclovir 450mg• To prevent CMV infection (if necessary)
• Antihypertensives
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Overview
• ESKD
• Why transplant?
• Transplant workup
• Transplant procedure
• Complications post transplant
• Kidney Donation
• How can general practice help ?
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Complications - early
• Surgical• Bleeding, wound infection
• Urine leak, thrombosis
• Other medical problems• Eg MI, DVT, chest infection
• Delayed function• ~30% of deceased kidneys
• <10% of living donor kidneys
• Acute rejection• 15% first month
• Treated with iv steroids
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Immunosuppression complications
• Infection • Bacteria (UTI common)
• Fungal (thrush)
• Viral (cold sores, shingles, CMV)
• Pneumocystis
•Cancer• Skin cancers +++++++++++++++++++++
• Lymphoma +
• Others (eg breast, cervical)
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Other late complications
• Ischaemic heart disease
• Post transplant diabetes
• Osteoporosis
• Graft loss• Chronic rejection (antibody mediated)
• Recurrent disease eg. GN, diabetes
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How long does a transplant last?
• Living donor kidneys do better overall• ~95% survival at one year
• Median survival 18 years
• Deceased donor kidney survival is a little less• ~90% survival at one year
• Median survival 15 years
• Survival also dependant on• Donor age, matching
• Vintage
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SurvivalCauses of death differ by modality. Withdrawal from dialysis dominates among older patients. Cancer dominates among younger people with a transplant.
020406080
100
0-44 45-64 65-74 75+ 0-44 45-64 65-74 75+ 0-44 45-64 65-74 75+
Haemodialysis Peritoneal dialysis Transplant
Cardiovascular Withdrawal Cancer
Infection Other
Pe
rce
nt
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Overview
• ESKD
• Why transplant?
• Transplant workup
• Transplant procedure
• Complications post transplant
• Kidney Donation
• How can general practice help ?
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Despite increases in donation rates, deceased donor Kidney Transplant is not a good bet…
• Getting on wait list for DD (work-up and eligibility)• 20% chance at 2 years
• 30% chance at 6 years
• Getting a kidney from the list (organ supply)• 13% chance at 2 years
• 30% chance at 6 years
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Kidney donors
• Deceased• Brain death
• After cardiac death
• Living• Related (eg sibling, parent)
• Unrelated, directed (eg wife, friend)
• Non-directed (anonymous)
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International Deceased Donor Rates (per million population) 2009
Int Med
2012
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Progress!
138 147 172113x̅=110
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Multiple Interventions• Education and raised awareness•Hard work by clinical teams - ODNZ/ICUs, Transplant
Centres, Referring Centres•Additional Direct Staffing
• Eg Donor Liaison Coordinators
•Project funding• South Auckland project• NRTS
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Expanding donor pool
• Non-directed donors
• DCD donors
• Marginal kidneys
• ABO incompatible transplants
• Paired kidney exchange
• Laparoscopic nephrectomy
• Donor reimbursement
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Live kidney donor transplantation
Laparoscopic hand assisted donor nephrectomy
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Kidney donors
Living donor(LD; directed)
Recipient identified (n=1)
Deceased donor(DBD, DCD)
Recipients “on the list” (n=500), Allocation nationally by waiting/matching
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Who can donate a kidney?
• Anyone who is healthy with 2 normal kidneys
• Not obese
• Not diabetic or high risk of diabetes
• Normal BP
• Seen by counsellor and Psychologist• No psych illness
• No coercion
• Understanding of risks
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Is kidney donation safe?
• Surgical/anaesthetics risk very low
• Increased long-term risks of • Hypertension • Preeclampsia
• ESKD 3:1000 (less than general population)
• Donors can benefit too• Lose burden of dialysis from home• Sense of fulfilment from life changing gift
• Patient autonomy is respected
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General Practice transplant care• Before transplant
• Early diagnosis of CKD and timely nephrology referral
• Attention to cardiovascular risks
• Encourage patients and donors to consider transplant
• After transplant• Encourage adherence
• Beware nephrotoxic or interacting drugs
• BP checks, diabetes screening
• Cancer screening and skin checks
• Fluvax after 1 year (avoid live vaccines)
• Bone density – usually check once at 1 yr
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Kidney transplant key points
• Transplantation is the best treatment for ESKD
• Should be the goal for most ESKD patients
• Tx is a big team effort
• GP has important role• Timely referral
• Adherence with meds
• Long-term management of complications
• Encourage consideration of transplantation and donation
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