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 lifeLower long term mortality riskFiscally responsible – vastly decreased

costs

Transplant Options

Cadaver

Living related

Living non related

Preparation for transplant

Stop smokingOptimal dialysisDon’t be fatBP controlDental care Exercise

Cadaver

Kidney donated by someone who is deceased – either by there pre death will or from family

Different team look after donor’s family and recipient’s family

Problem with ‘down’ time – ischaemic time

Cadaver kidney source

Cause of Donor Death

563 574

743

164129 139121 125

245

30 35 15

250261

385

1989-1994 1995-2000 2001-2007

CerebrovascularTrauma-RoadTrauma-Non RoadOtherCerebral Tumour

Donation after Cardiac Death

ICU Following cessation

treatment On Registry Pre family consent

Living

Higher success rate 5-10%May need fewer anti-rejection drugsCan plan the operation at a suitable timeNo ‘down’ time

Source of Live Donor KidneyAustralia 1999 - 2007

169 181213 230

218244 246

273 271

1999 2000 2001 2002 2003 2004 2005 2006 2007

Unrelated

Related

Advantages of living donor Transplant

Better resultsLong wait for cadaveric kidneyRelieves stress on cadaveric donor

supplyEmotional gain to donorPlanning convenience

Donor complications

PnemothoraxBlood transfusionThrombosis – DVT, PEPneumoniaInfections – wound, urineKidney failure – laterOther – AMI, Bowel obstructinRisk of dying 3 in 10,000

Complications for recipient

RejectionInfectionCancerHypertension

Disadvantages of live donor Transplant

Operative mortality 3 in 10 000Major post op complications 2%Minor post op complications 50%Risk of traumatic injury to single kidneyMinimise 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

Blood Type Can receive kidney from:

Generally can donate a kidney to:

O O O, A, B, AB

A A, O A, AB

B B, O B, AB

AB O, A, B, AB AB

Cadaveric Donor Matching

Blood Group CompatibleTissue Typing - A, B, AB, OAntibodiesTime on Dialysis CrossmatchLong 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?

DONORRECIPIENT

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

What…does the future hold?

Altruistic donors to make a chainDutch experience.US experience, how far can it go?More states involved…even nationwide.

Kidney Transplant

First one in 1954 in BostonIdentical twinsMore than 600 in Australia last year

Figure 7.3

Patients on Waiting Lis t Related to Race and Age <65 years 31-Dec-2007

QLD NSW ACT VIC TAS SA NT WA AUST NZ

Caucasoid 85 391 32 240 15 49 2 53 867 138

Aboriginal/TSI 8 13 1 0 0 5 1 21 49 0

Maori 0 6 0 3 0 0 0 0 9 46

Pacific People 1 15 0 5 0 0 0 0 21 34

Asian 12 110 3 48 0 2 1 12 188 24

Other 2 11 1 8 0 0 0 3 25 2

Total 108 546 37 304 15 56 4 89 1159 244

Waitlist

1800 on national organ transplant waiting lists – half for kidneys

Average wait 3-4 years

Medications used

Cyclosporine TacrolimusSirolimusAzathioprineMycophenolate Mofetil Prednisone OKT3 Antithymocyte Ig (ATGAM)

Cyclosporin (Neoral)

1980’sVast improvement in graft successBlocksSide 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 tacrolimus-FKBP-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 FK506Cyclosporin

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 fibrosisHyaline arteriolopathyFocal 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 Azathioprine1995Side effects; diarrhoea,constipation,

nausea, indigestion, fluid retention

Prednisolone

SteroidHigh doses initially and then weaned

Side 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 suitable65 - 70 yearsScreening ProtocolCardiac and Medical Risk Categories

High Cardiac Risk

Cardio, cerebro or peripheral vascular disease

DMage >55significant smoking historyIndigenous

High Medical Risk

Severe chronic lung diseaseHistory malignancyActive infection PUDMental illness/ poor complianceObesityPrior transplants

Pre op Care

IsolationImmunosuppression- quadruple or tripleSteroidsIV FluidsECG, ? Dialysis

Intra op/ Recovery

CVC and IDCIVAB prophylaxis- cefazolin 1GIV Frusemide 80mg at cross clamp

releaseMannitol and albuminMinimise ischaemic timePink + 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 12-

15 Pain, nausea, resp, vital signs U&E, K+,Hb, BSL Renal ultrasound and doppler

Ward Care

Immunosuppression- daily levelsDiltiazem, AB proph, famotidine, statin,

+/- lasix, CMV prophRemoval of IV, CVC, IDC day 2-3Biopsy if signs of rejectionDischarge 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

PlasmapharesisImmunoadsorption columnTitresRituximabHigher riskMade in Japan

Following Nephrectomy for Renal Cell Carcinoma

ALTRUISTIC DONORALTRUISTIC DONOR

REMOVED KIDNEY REMOVED KIDNEY (WITH TUMOUR) (WITH TUMOUR)

FROM DONORFROM DONOR

TUMOUR REMOVED TUMOUR REMOVED FROM KIDNEY PRIOR TO FROM KIDNEY PRIOR TO

TRANSPLANTING TRANSPLANTING INTO RECIPIENTINTO RECIPIENT

HEALTHY KIDNEY HEALTHY KIDNEY TRANSPLANTED TRANSPLANTED INTO RECIPIENTINTO RECIPIENT

TUMOUR SENT FOR TUMOUR SENT FOR MICROSCOPIC MICROSCOPIC EXAMINATIONEXAMINATION

2008 in WA

25 live donors – x2 ABOi6 tumour resected/altruistic1 altrustic7 Kidney exchange41 cadaveric.

Total of 80 transplants in WA.

KIDNEYS FOR SALE

Internet

MatchingOrgans.Com

Xenotransplantation

Signs of rejection

FeverMalaiseTenderness over the kidneyHypertensionIncreased creatinine

CMV

Belongs to a group of herpesvirusesCommon80% adults show seropositivity to

infectionMost common viral infection following

renal transplantCMV infection – detected without

evidence of diseaseCMV 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 WargerCARI guidelinesRPH protocolsKidney Health AustraliaAIHW websiteChronic Kidney Disease in Australia

2009