Dr David McGregorClinical Director/Nephrologist

Christchurch Hospital

Christchurch

11:00 - 11:30 Renal Transplantation Basics

Kidney Transplantation

Dr David McGregor

Department of Nephrology

Christchurch Hospital

Overview

• ESKD

• Why transplant?

• Transplant workup

• Transplant procedure

• Complications post transplant

• Kidney Donation

• How can general practice help ?

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

More patients with treated ESKD each year

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

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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

Treatment Options

• Haemodialysis

• Peritoneal Dialysis

• Kidney Transplant

• Supportive Care (= Palliative Care)

Benefits of kidney transplantation

1-Quality of Life much better with transplant

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

Complications of ESKD

• Anaemia

• Bone disease – PTH, osteomalacia

• Abnormal calcifications

• Accelerated atherosclerosis

• Depression, inability to work

• Most improved with transplant

2 - Survival is better with a transplant

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

3 –Transplants less expensive

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%

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

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

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

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

Overview

• ESKD

• Why transplant?

• Transplant workup

• Transplant procedure

• Complications post transplant

• Kidney Donation

• How can general practice help ?

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

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

Deceased donor kidney waiting list and allocation

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

*

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

Allocation

Overview

• ESKD

• Why transplant?

• Transplant workup

• Transplant procedure

• Complications post transplant

• Kidney Donation

• How can general practice help ?

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

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

Post transplant care

• Usually discharge day 5-7

• Daily OP visits for first month

• Then reducing frequency

• After 1 year reviewed 3-6 monthly

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

Prednisone

• Dose dependent

• Worse early

• Progressive dose reduction

• Patients hate SE’s but stopping = risk of rejection

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

Other medicines after transplant

• Iron

• Omeprazole

• Sulphamethoxazxole/Trimethoprim• To prevent PCP lung infection

• Valganciclovir 450mg• To prevent CMV infection (if necessary)

• Antihypertensives

Overview

• ESKD

• Why transplant?

• Transplant workup

• Transplant procedure

• Complications post transplant

• Kidney Donation

• How can general practice help ?

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

Immunosuppression complications

• Infection • Bacteria (UTI common)

• Fungal (thrush)

• Viral (cold sores, shingles, CMV)

• Pneumocystis

•Cancer• Skin cancers +++++++++++++++++++++

• Lymphoma +

• Others (eg breast, cervical)

Other late complications

• Ischaemic heart disease

• Post transplant diabetes

• Osteoporosis

• Graft loss• Chronic rejection (antibody mediated)

• Recurrent disease eg. GN, diabetes

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

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

Overview

• ESKD

• Why transplant?

• Transplant workup

• Transplant procedure

• Complications post transplant

• Kidney Donation

• How can general practice help ?

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

Kidney donors

• Deceased• Brain death

• After cardiac death

• Living• Related (eg sibling, parent)

• Unrelated, directed (eg wife, friend)

• Non-directed (anonymous)

International Deceased Donor Rates (per million population) 2009

Int Med

2012

Progress!

138 147 172113x̅=110

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

Expanding donor pool

• Non-directed donors

• DCD donors

• Marginal kidneys

• ABO incompatible transplants

• Paired kidney exchange

• Laparoscopic nephrectomy

• Donor reimbursement

Live kidney donor transplantation

Laparoscopic hand assisted donor nephrectomy

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

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

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

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

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