Introduction Introduction to to

Kidney Kidney TransplantationTransplantation

Dr Natasha CookDr Natasha CookRenal Physician, Austin Health and Northern HealthRenal Physician, Austin Health and Northern Health

September 2009 September 2009

Treatment for Kidney Treatment for Kidney FailureFailure

DialysisDialysis:: Haemodialysis Haemodialysis & & PeritonealPeritoneal

TransplantTransplantationation

A kidney transplant is only one A kidney transplant is only one type of treatment for End Stage type of treatment for End Stage Renal Failure. Renal Failure.

It is NOT a cureIt is NOT a cure

Where does my new kidney go?

Where does my new kidney go?Where does my new kidney go?

Kidney Transplant - Kidney Transplant - AdvantagesAdvantages

What are the benefits of a kidney What are the benefits of a kidney transplant?transplant?

Quality of Life:Quality of Life: normal life normal life NoNo dialysis dialysis Back to wBack to work, holiday etc. ork, holiday etc. Food and fluid intake less restrictedFood and fluid intake less restricted Improved sexual function and fertilityImproved sexual function and fertility

Improved Medical Outcome:Improved Medical Outcome: Increased longevity in the majority of Increased longevity in the majority of patientspatients

Short Term Risks of Short Term Risks of TransplantationTransplantation

Anaesthesia and surgical complications:Anaesthesia and surgical complications: including infection (wound, pneumonia, including infection (wound, pneumonia,

urine infections), urine infections), bleeding, bleeding, clots in the legs and lungs.clots in the legs and lungs. death death

Donors are screened thoroughly for Donors are screened thoroughly for infections and cancers, however unknown infections and cancers, however unknown infectious agents and microscopic cancers infectious agents and microscopic cancers in the donor which are not detectable may in the donor which are not detectable may be transmitted to the recipient. This is be transmitted to the recipient. This is very uncommon. very uncommon.

Risks of Risks of Transplantation Transplantation

Complications from the anti-rejection medicationsComplications from the anti-rejection medications

Infections overall and includes infectious Infections overall and includes infectious organisms which the general population would not organisms which the general population would not normally acquire (“opportunistic infections” eg. normally acquire (“opportunistic infections” eg. Viral, fungal, atypical – examples are Viral, fungal, atypical – examples are Cytomegalovirus, Pneumocystis)Cytomegalovirus, Pneumocystis)

Cancers in general are increased in transplant Cancers in general are increased in transplant recipients; especially skin cancers and lymphoid recipients; especially skin cancers and lymphoid cancerscancers

Diabetes Diabetes High blood pressureHigh blood pressure High cholesterol and other lipidsHigh cholesterol and other lipids OsteoporosisOsteoporosis Specific side-effects of each anti-rejection Specific side-effects of each anti-rejection medicationmedication

Kidney Transplant – Other Kidney Transplant – Other considerationsconsiderations

Hospital stay is usually about 1 week but Hospital stay is usually about 1 week but complications can lead to a longer stay or coming complications can lead to a longer stay or coming back into hospitalback into hospital

Delayed Graft Function : You may need dialysis Delayed Graft Function : You may need dialysis for a while until your kidney starts to work for a while until your kidney starts to work

RejectionRejection InfectionInfection Technical Problems with Surgery at the blood Technical Problems with Surgery at the blood vessel or the bladder endvessel or the bladder end

Frequent visits to clinic, frequent blood tests.Frequent visits to clinic, frequent blood tests. It may take some time before you feel the It may take some time before you feel the

benefitsbenefits..

Ongoing issues and changes to Kidney Transplantation

Supply and Demand - increasing waiting time on deceased donor waiting list (Currently about 3-6 years depending on blood group and antibody level)

Changes to Practice due donor organ shortage

•Increasing Live Donor Transplantation•Transplantation of patients with “positive cross-match”•ABO incompatible transplantation •Paired exchange

Significant changes to anti-rejection therapy

Types of TransplantsTypes of Transplants Deceased Donor TransplantsDeceased Donor Transplants Live DonorLive Donor

Related (genetic)Related (genetic) Unrelated (“emotionally”)Unrelated (“emotionally”)

OtherOther Live Non-directed donationLive Non-directed donation Paired ExchangePaired Exchange

0

100

200

300

400

500

600

700

<1 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 >32

Duration in Years

Deceased (4478)

Live (2061)

Number and Duration of Functioning Grafts Australia 2005

All Functioning Grafts (6,269)

Deceased Donor Deceased Donor TransplantsTransplants

How are the kidneys obtained?How are the kidneys obtained?The Donor Transplant Coordinator facilitates, The Donor Transplant Coordinator facilitates, coordinates and assists in the procurement coordinates and assists in the procurement of donor organs 24 hours a day.of donor organs 24 hours a day.

Provides the link between the donor Provides the link between the donor hospital and the transplant hospitalhospital and the transplant hospital

Receives referrals from Intensive Care Receives referrals from Intensive Care Units who believe they may have a potential Units who believe they may have a potential donordonor

Attends the referring hospital to assist in Attends the referring hospital to assist in organising the donationorganising the donation

Who is eligible for a Who is eligible for a transplant?transplant?

FFor people who are or people who are NearNear ddialysisialysis or d or dialysis dependentialysis dependent

Medically Medically & Surgically & Surgically FitFit

Transplant is Transplant is NOTNOT a suitable a suitable treatment treatment for everyonefor everyone

AgeAge It’s not the age in years that count but It’s not the age in years that count but how worn your body is or how many other how worn your body is or how many other disease you have.disease you have.

The Transplant List

There is only ONE Transplant List which is the “Active Transplant List” – ready to be called for transplantation

Interim Patients under consideration or temporarily off the Active List do NOT appear on the active transplant list

Transplant Waiting List Transplant Waiting List RequirementsRequirements

22ndnd Monthly Monthly blood test for antibodiesblood test for antibodies

YearlyYearly Transplant Review Transplant Review Review Review recipients recipients due to increasing due to increasing waiting timewaiting time

Medical & Surgical fitnessMedical & Surgical fitness

Education Seminar every 2 yearsEducation Seminar every 2 years Update on new developmentsUpdate on new developments Update on Risks/Benefits of Update on Risks/Benefits of TransplantationTransplantation

Transplant “Work Up”Transplant “Work Up”

Transplant Doctor & Transplant Transplant Doctor & Transplant Nurse in Transplant Outpatient Nurse in Transplant Outpatient ClinicClinic

Detailed History and ExaminationDetailed History and Examination Blood tests Blood tests X raysX rays Heart TestsHeart Tests Check up by Transplant SurgeonCheck up by Transplant Surgeon Referrals to other specialists as Referrals to other specialists as needed- Cardiac, Gastroenterology, needed- Cardiac, Gastroenterology, Dermatology, Liver, Psychiatrists, Dermatology, Liver, Psychiatrists, Vascular SurgeonsVascular Surgeons

Tissue Typing and Cytotoxic Tissue Typing and Cytotoxic antibodiesantibodies

Tissue typingTissue typing identifies identifies Transplantation Transplantation or Tissue or Tissue antigensantigens Must be completed before acceptance Must be completed before acceptance onto the transplant listonto the transplant list

Cytotoxic AntibodiesCytotoxic Antibodies (antibody to (antibody to “Transplantation or Tissue” antigen)“Transplantation or Tissue” antigen) Monthly testMonthly test Patient removed from the transplant Patient removed from the transplant list if blood is not received list if blood is not received regularlyregularly

Living Donor Living Donor TransplantsTransplants

Donor WorkupDonor Workup

Living Donor Living Donor TransplantsTransplants

Who can donate? Who can donate?

Parents, brothers, sisters, Parents, brothers, sisters, cousins, husbands, wives, cousins, husbands, wives, friends.friends.

Live Donor TransplantsLive Donor Transplants

The Donor is the very important The Donor is the very important person in this situation and person in this situation and every possible care is taken to every possible care is taken to make sure make sure any potential riskany potential risk is is minimised to acceptable levels minimised to acceptable levels

Individuals who may be excluded Individuals who may be excluded for living donationfor living donation

Age – the elderlyAge – the elderly Women who have not completed childbearing: preferably Women who have not completed childbearing: preferably

not usednot used Diabetes – complete contraindicationDiabetes – complete contraindication Obesity/overweightObesity/overweight Renal disease complete contraindicationRenal disease complete contraindication

Abnormal GFR. (The volume of urine filtered by the kidney over Abnormal GFR. (The volume of urine filtered by the kidney over a set time)a set time)

Protein in the urineProtein in the urine Kidney stonesKidney stones Kidney surgeryKidney surgery RefluxReflux High Blood PressureHigh Blood Pressure Blood in the urineBlood in the urine

Heart diseaseHeart disease Lung diseaseLung disease CancerCancer InfectionInfection Inability to give consentInability to give consentThe donation must not be coerced and must be truly The donation must not be coerced and must be truly

altruistic.altruistic.

Live Kidney Donor WorkupLive Kidney Donor Workup

Blood testsBlood tests Urine tests: to check for blood Urine tests: to check for blood and protein and protein

Special Kidney XraysSpecial Kidney Xrays Ultrasound of kidneys and urinary tractUltrasound of kidneys and urinary tract Renal ScanRenal Scan CT CT AngiogramAngiogram

Review by Transplant Surgeon, Review by Transplant Surgeon, Psychiatrist and Independent Psychiatrist and Independent Renal PhysicianRenal Physician

Donor NephrectomyDonor Nephrectomy

Post Transplant Follow Post Transplant Follow upup

Maximising Survival of the Maximising Survival of the kidneykidney

Factors that we watch for, which Factors that we watch for, which may contribute to poor function:may contribute to poor function:

Kidney Rejection (Early and Late)Kidney Rejection (Early and Late) Drug ToxicityDrug Toxicity Proteinuria Proteinuria Poorly controlled blood pressurePoorly controlled blood pressure BK virus infectionBK virus infection

Post Transplant Post Transplant ComplicationsComplications

InfectionInfection PCP pneumonia: Bactrim 3 times weekly or PCP pneumonia: Bactrim 3 times weekly or nebulised pentamadine for 6 monebulised pentamadine for 6 mo

CMV: anti-viral treatment depending on CMV: anti-viral treatment depending on exposure status of donor and recipientexposure status of donor and recipient

Recurrence of kidney diseaseRecurrence of kidney disease Diabetic nephropathyDiabetic nephropathy Glomerulonephritis (Primary or Secondary)Glomerulonephritis (Primary or Secondary)

Cardiovascular diseaseCardiovascular disease Diabetes (prednisolone, tacrolimus)Diabetes (prednisolone, tacrolimus) Cancer: Screening, Dermatology reviewCancer: Screening, Dermatology review Osteoporosis: 2 yearly DEXA scan Osteoporosis: 2 yearly DEXA scan

Other Health IssuesOther Health Issues

ObesityObesity SmokingSmoking DietDiet Issues relating to FertilityIssues relating to Fertility

Transplantation issues Transplantation issues in Alport Syndromein Alport Syndrome

Transplantation is an Transplantation is an Excellent Treatment for End Excellent Treatment for End Stage Renal Failure due to Stage Renal Failure due to

Alport SyndromeAlport Syndrome

Anti-Glomerular Basement Anti-Glomerular Basement Membrane Antibody diseaseMembrane Antibody disease

2-3% risk of graft loss due to 2-3% risk of graft loss due to formation of anti-Glomerular formation of anti-Glomerular Basement Membrane Antibodies in Basement Membrane Antibodies in male transplant recipients with male transplant recipients with Alport SyndromeAlport Syndrome

Anti-Glomerular Basement Anti-Glomerular Basement Membrane Antibody diseaseMembrane Antibody disease

The glomerular basement membrane in The glomerular basement membrane in the kidney is made of Type 4 Collagenthe kidney is made of Type 4 Collagen

Production of components ofProduction of components of type IV type IV collagen is reduced or defective in collagen is reduced or defective in Alport SyndromeAlport Syndrome

When normal components are encountered When normal components are encountered in the new kidney by a recipient with in the new kidney by a recipient with Alport Syndrome, they are seen as Alport Syndrome, they are seen as foreign and antibodies can be formed foreign and antibodies can be formed

This leads to glomerulonephritis and This leads to glomerulonephritis and graft lossgraft loss

Anti-Glomerular Basement Anti-Glomerular Basement Membrane Antibody diseaseMembrane Antibody disease

Men with deafness and kidney failure before Men with deafness and kidney failure before 30 years of age are more susceptible30 years of age are more susceptible

COL4A5 deletions (The gene encoding COL4A5 deletions (The gene encoding αα5 5 chain of Type IV collagen)chain of Type IV collagen) are associated are associated with higher riskwith higher risk

However studies generally find the risk of However studies generally find the risk of anti-GBM nephritis is still less than anti-GBM nephritis is still less than predictedpredicted

Plasma exchange, cyclophosphamide and more Plasma exchange, cyclophosphamide and more recently rituximab are treatment optionsrecently rituximab are treatment options

Difficult to treat Difficult to treat

Anti-Glomerular Basement Anti-Glomerular Basement Membrane Antibody DiseaseMembrane Antibody Disease

Bone marrow plus Kidney Bone marrow plus Kidney transplantation:transplantation:

Recipient’s immune system is a mixture Recipient’s immune system is a mixture of cells from the native and donor of cells from the native and donor immune systemimmune system

Immune cells do not react against the Immune cells do not react against the kidney transplant kidney transplant

Use of Alport ‘Carriers’ Use of Alport ‘Carriers’ with isolated haematuria with isolated haematuria

as Renal Donorsas Renal Donors One recently published study with One recently published study with very small numbers but follow up very small numbers but follow up for 2-14 years:for 2-14 years:

Gross et al NDT May 2009:Gross et al NDT May 2009: 6 “Carrier” mothers donating to sons6 “Carrier” mothers donating to sons 3/6 new high blood pressure3/6 new high blood pressure 2/6 new protein in the urine2/6 new protein in the urine 4/6 decline in kidney function (but 4/6 decline in kidney function (but kidney function still about 40% or kidney function still about 40% or more of normal)more of normal)

Use of Alport ‘Carriers’ Use of Alport ‘Carriers’ with isolated microscopic with isolated microscopic haematuria as Renal Donorshaematuria as Renal Donors Significant risk of Significant risk of

New Onset ProteinuriaNew Onset Proteinuria New Onset HypertensionNew Onset Hypertension Decline in Renal functionDecline in Renal function

HEARING LOSS, PROTEINURIA, HEARING LOSS, PROTEINURIA, HYPERTENSION, OR KIDNEY FAILURE HYPERTENSION, OR KIDNEY FAILURE PRIOR TO DONATION ARE ABSOLUTE PRIOR TO DONATION ARE ABSOLUTE CONTRAINDICATIONSCONTRAINDICATIONS

Use of Alport ‘Carriers’ Use of Alport ‘Carriers’ with isolated microscopic with isolated microscopic haematuria as Renal Donorshaematuria as Renal Donors

Should be a rare eventShould be a rare event Close follow up is requiredClose follow up is required Donors should be given ACE Donors should be given ACE inhibitors (which reduce inhibitors (which reduce protein leak into the urine as protein leak into the urine as well as blood pressure)well as blood pressure)

Questions?Questions?