Renal Transplantation

Cherelle Fitzclarence
6.2009

Kidney Transplantation

Why Transplant?
Figures
Cadaveric/Live donors
Donor Criteria
Recipient criteria
Post Op management
Medications
Issues to consider
Workup

Why Transplant?
Quality

of life
Lower long term mortality risk
Fiscally responsible vastly decreased
costs

Transplant Options
Cadaver
Living

related

Living

non related

Preparation for transplant

Stop

smoking
Optimal dialysis
Dont be fat
BP control
Dental care
Exercise

Cadaver
Kidney

donated by someone who is

deceased either by there pre death will
or from family
Different team look after donors family
and recipients family
Problem with down time ischaemic
time

Cadaver kidney source

Cause of Donor Death

Donation after Cardiac Death

ICU
Following

cessation

treatment
On Registry
Pre family consent

Living
Higher

success rate 5-10%

May need fewer anti-rejection drugs
Can plan the operation at a suitable time
No down time

Source of Live Donor Kidney

Australia 1999 - 2007

Advantages of living donor

Transplant
Better

results
Long wait for cadaveric kidney
Relieves stress on cadaveric donor
supply
Emotional gain to donor
Planning convenience

Donor complications
Pnemothorax
Blood

transfusion
Thrombosis DVT, PE
Pneumonia
Infections wound, urine
Kidney failure later
Other AMI, Bowel obstructin
Risk of dying 3 in 10,000

Complications for recipient

Rejection
Infection
Cancer
Hypertension

Disadvantages of live donor

Transplant
Operative

mortality 3 in 10 000
Major post op complications 2%
Minor post op complications 50%
Risk of traumatic injury to single kidney
Minimise risk factors to prevent future
health problems

Disadvantages of live donor

transplant
Psychological Stress

Exclusion Criteria - For Donation

Hypertensive
Diabetic
proteinuria,

haematuria
Hx recurrent kidney stones
Significant medical illness
Hx thrombosis, thromboembolism
Strong family Hx renal disease, diabetes, high
BP
Healthy weight

Exclusion Criteria - For Donation

<18
>65

ABO compatibility

Cadaveric Donor Matching

Blood

Group Compatible
Tissue Typing - A, B, AB, O
Antibodies
Time on Dialysis
Crossmatch
Long term waiters

Other option

Who?
Pt

must be eligible for a kidney transplant.

Recipient must have a living donor(s) who are
willing but unable to donate because of ABO
incompatibility or a positive crossmatch.
Donors must be willing to take part and willing
to donate their kidney to another person.
Cadaver organ available
Common blood groups with low sensitisation
have greater chance.

How?
DONOR

RECIPIENT
Mr

One

Ms One

Mr

Two

Mrs Two

Chains
DONORS

RECIPIENTS

Mr

G Samaritan

Ms One

Mr

One Mrs two

Mr

Two Ms C Waitlist

Whatdoes the future hold?

Altruistic

donors to make a chain

Dutch experience.
US experience, how far can it go?
More states involvedeven nationwide.

Kidney Transplant
First

one in 1954 in Boston

Identical twins
More than 600 in Australia last year

Waitlist
1800

on national organ transplant

waiting lists half for kidneys
Average wait 3-4 years

Medications used
Cyclosporine
Tacrolimus
Sirolimus
Azathioprine
Mycophenolate

Mofetil

Prednisone
OKT3
Antithymocyte

Ig (ATGAM)

Cyclosporin (Neoral)
1980s
Vast

improvement in graft success

Blocks
Side effects; hirsutism, gum hypertrophy,
liver impairment, fatigue,
hyperlipidaemia, nausea, hypertension

Tacrolimus (Prograf)

Tacrolimus is a macrolide lactone with potent in vitro and in vivo

immunosuppressive activity.
Studies suggest that tacrolimus inhibits the formation of cytotoxic
lymphocytes which are regarded as being primarily responsible for graft
rejection.
Tacrolimus suppresses T cell activation and T helper cell dependent B
cell proliferation, as well as the formation of lymphokines such as
interleukins-2 and 3 and gamma-interferon and the expression of the
interleukin-2 receptor.
At the molecular level, the effects of tacrolimus appear to be mediated by
binding to a cytosolic protein (FKBP) which is responsible for the
intracellular accumulation of the compound. A complex of tacrolimusFKBP-12, calcium, calmodulin and calcineurin is formed and the
phosphatase activity of calcineurin inhibited.
Side Effects; Tremor, hypertension, nausea, renal impairment, diabetes

Tacrolimus
Higher

rate of diabetes, gastro

symptoms and neurological symptoms
Similar risk rate to cyclosporin for
infection and post transplant malignancy

Sirolimus (Rapamune)
Sirolimus

inhibits T cell activation induced by

most stimuli by blocking calcium dependent
and calcium independent intracellular signal
transduction.
Studies demonstrated that its effects are
mediated by a mechanism that is different
from that of cyclosporin, tacrolimus and other
immunosuppressive agents.

Calcineurin Inhibitors
Tacrolimus

FK506
Cyclosporin

Complications
Tacrolimus

and cyclosporin both can be

associated with chronic allograft
nephropathy (CAN)
Acute rejection on cyclosporin may be
able to be salvaged with a switch to
tacrolimus

Complications
Interleukin

2 mediated activation of
lymphocytes is a critical factor in the
cellular immune response of acute
kidney transplant rejection
Decreased loss of allograft at 12 months
in pts treated with tacrolimus as opposed
to cyclosporin

Calcineurin Inhibitor Nephrotoxicity

Gold

standard for diagnosis is renal

allograft biopsy

Acute calcineurin nephrotoxicity

Related

to haemodynamic changes on
the afferent arteriole which are dose
dependent and reversible

Chronic calcineurin
nephrotoxicity
Focal

or striped tubulo-interstitial fibrosis

Hyaline arteriolopathy
Focal collapsing glomerulosclerosis

Diltiazem

Antihypertensive
Increases available levels of anti rejection drugs via
the hepatic metabolism pathway
Inhibit the influx of calcium ions during membrane
depolarisation of cardiac and vascular smooth muscle
Produces its antihypertensive effects primarily by
relaxation of vascular smooth muscle and the resultant
decrease in peripheral vascular resistance. The
magnitude of blood pressure reduction is related to the
degree of hypertension

Azathioprine
Used

in combination with cyclosporin or

tacrolimus or sirolimus
Side effects; skin rash , myalgias, fever,
headache, vomiting

Mycophenolate (Cellcept)
Can

be used instead of Azathioprine

1995
Side effects; diarrhoea,constipation,
nausea, indigestion, fluid retention

Prednisolone
Steroid
High
Side

doses initially and then weaned

effects; weight gain, increased

appetite, high blood sugars, diabetes,
delayed wound healing, muscle wasting,
osteoporosis

Bactrim
Antibacterial

Meds and pregnancy

Trough

levels of cyclosporin tend to drop in

later pregnancy
Acute rejection decreased risk despite lower
levels
High level of 2 year post pregnancy graft loss
Miscarriage, prematurity, low birth weight,
preeclampsia risks are increased
Bubs have suppressed innate immunity
Excreted in breast milk same level as
maternal blood levels

Live Donation Steps

ID of suitable recipient.
Medical and surgical history, blood group, FBP,
renal function, LFT, chol, coags, urine tests.
Immunological and viral tests
Establish compatibility
CXR, ECG, psych review

Surgical review/ Surgery

Usually left kidney b/o

longer renal vein.
Assessed post Spiral CT
scan
Lap or Open. 2-3 hrs
Inpatient 3 to 7 days
Annual reviews of renal
function

Recipient Criteria
1/3

ESRF pts suitable

65 - 70 years
Screening Protocol
Cardiac and Medical Risk Categories

High Cardiac Risk

Cardio,

cerebro or peripheral vascular

disease
DM
age >55
significant smoking history
Indigenous

High Medical Risk

Severe

chronic lung disease

History malignancy
Active infection
PUD
Mental illness/ poor compliance
Obesity
Prior transplants

Pre op Care
Isolation
Immunosuppression Steroids
IV

Fluids
ECG,
? Dialysis

quadruple or triple

Intra op/ Recovery

CVC

and IDC
IVAB prophylaxis- cefazolin 1G
IV Frusemide 80mg at cross clamp
release
Mannitol and albumin
Minimise ischaemic time
Pink + output

Immediate Post Op
PCA,

redivac, CVC, IV access, IDC, wound

Monitor blood loss- drain, swelling, wound
dressing, hypotension
Urine output + fluid balance hourly, CVP 1215
Pain, nausea, resp, vital signs
U&E, K+,Hb, BSL
Renal ultrasound and doppler

Ward Care
Immunosuppression-

daily levels
Diltiazem, AB proph, famotidine, statin,
+/- lasix, CMV proph
Removal of IV, CVC, IDC day 2-3
Biopsy if signs of rejection
Discharge 5 -7 days

Long Term Management

Education
Daily

clinic visits 2 weeks

First 3 months are Hell!
Monitor for signs of rejection
JJ stent removal 5-6 weeks
BP, Chol, BSL, CMV
Cancer screenings- skin checks, pap smears,
mammograms
Dental, weight, diet

Options to consider?

Kidney Exchange
Pool of

Recipients/Donors
Consent
Going national in
July

ABO incompatible donation

Plasmapharesis
Immunoadsorption
Titres
Rituximab
Higher

risk
Made in Japan

column

Following Nephrectomy for

Renal Cell Carcinoma

ALTRUISTIC DONOR

REMOVED KIDNEY
(WITH TUMOUR)
FROM DONOR

TUMOUR REMOVED
FROM KIDNEY PRIOR TO
TRANSPLANTING
INTO RECIPIENT

HEALTHY KIDNEY
TRANSPLANTED
INTO RECIPIENT

TUMOUR SENT FOR

MICROSCOPIC
EXAMINATION

2008 in WA
25

live donors x2 ABOi

6 tumour resected/altruistic
1 altrustic
7 Kidney exchange
41 cadaveric.
Total of 80 transplants in WA.

KIDNEYS FOR SALE

Internet

MatchingOrgans.Com

Xenotransplantation

Signs of rejection
Fever
Malaise
Tenderness

over the kidney

Hypertension
Increased creatinine

CMV
Belongs

to a group of herpesviruses
Common
80% adults show seropositivity to
infection
Most common viral infection following
renal transplant
CMV infection detected without
evidence of disease
CMV disease evidence of organ
damage

CMV
Disease

characterised by fever,
mononucleosis, leucopaenia,
thrombocytopaenia
Pneumonitis, hepatitis, encephalitis, focal
gastrointestinal disease
Ganciclovir is the treatment of choice for
disease and should be given IV at least 2
weeks
Alternative is valganciclovir orally 10 times
the bioavailablity

CMV
CMV

disease associated with increased

morbidity and mortality
CMV infection is associated with
increased rejection and bacterial and
fungal infection
Treatment is associated with better
outcomes

CMV
Prophylactic

treatment of CMV is
recommended in solid organ transplant
Oral valaciclovir, oral or Iv ganciclovir or
or valganciclovir all equally effective
Indicated if donor positive and recipient
positive or negative

CMV

Acknowledgements
Anne

Warger
CARI guidelines
RPH protocols
Kidney Health Australia
AIHW website
Chronic Kidney Disease in Australia
2009