RENAL TRANSPLANTATION

The best treatment for patients with ESRD

NEPHROLOGY UNITUITH, ILORIN

• Renal transplantation is the organ transplant of a kidney into a patient with end-stage renal disease.

• Kidney transplantation is typically classified as deceased-donor or living-donor transplantation depending on the source of the donor organ.

• Living-donor renal transplants are further characterized as genetically related (living-related) or non-related (living-unrelated) transplants, depending on whether a biological relationship exists between the donor and recipient.

INDICATIONS•The indication for kidney transplantation is end-stage renal disease (ESRD), regardless of the primary cause.

•This is defined as a glomerular filtration rate <15ml/min/1.73 sq.m.

CHRONIC KIDNEY DISEASE•All individuals with a glomerular filtration rate (GFR) <60 mL/min/1.73 m2 for 3 months are classified as having chronic kidney disease, irrespective of the presence or absence of kidney damage.

•The rationale for including these individuals is that reduction in kidney function to this level or lower represents loss of half or more of the adult level of normal kidney function, which may be associated with a number of complications.

• All individuals with kidney damage persisting for 3 or more months are classified as having chronic kidney disease, irrespective of the level of GFR.

• The rationale for including individuals with GFR >

60 mL/min/1.73 m2 is that GFR may be sustained at normal or increased levels despite substantial kidney.

STAGES OF CHRONIC KIDNEY DISEASEStage 1•kidney damage with normal or relatively high GFR (≥90 mL/min/1.73 m2). Stage 2•Mild reduction in GFR (60–89 mL/min/1.73 m2) with kidney damage. Stage 3•Moderate reduction in GFR (30–59 mL/min/1.73 m2). Stage 4•Severe reduction in GFR (15–29 mL/min/1.73 m2)Stage 5• End stage renal disease (ESRD) (GFR <15 mL/min/1.73 m2

• Sources of kidneys: DeceasedLiving related Living unrelated

Organ trade•In the developing world some people sell their organs. Such people are often in grave poverty or are exploited by salespersons.• The people who travel to make use of these kidneys are often known as "transplant tourists." •This practice is opposed by a variety of human rights groups, including Organs Watch, a group established by medical anthropologists, which was instrumental in exposing illegal international organ selling rings.

RECIPIENT EVALUATION• Must have established ESRD without any

potentially reversible component• Recipient should have a life expectancy > 5 years• No evidence of active infection• No evidence of active malignant disease• Psychiatric evaluation is very important to

establish motivation and likelihood of compliance and absence of substance abuse

• Most transplant recipients are between 15 – 50yrs however age is no longer a barrier

RECIPIENT EVALUATION

• Absolute contraindications1. Presence of potentially harmful antibodies

against the donor kidney2. Antibodies against the ABO blood group

antigens3. Antibodies against HLA class 1 and class II

antigens

TISSUE TYPING

• HLA antigens are the major transplantation antigens

• These genes are located in the short arm of chromosome 6 at the site termed the MHC

• The genes code for 2 classes of HLA antigens which are glycoproteins on the surface of all cells

• Class 1 HLA antigens (HLA – A, B, C) can be detected on most cells, they are target for cytotoxic T lymphocytes (CD8+)

TISSUE TYPING

• Class II HLA antigens (HLA DR) are restricted to B cells, monocytes/ macrophages. They are involved in immune recognition and regulation of immune responsiveness

• HLA typing is important in evaluating family members as kidney donors

• The degree of match is an important consideration in choosing an appropriate donor among family members

TISSUE TYPING

• The concentration of HLA genes in one defined area of chromosome are inherited as a packet or haplotype

• Each individual inherits one haplotype of HLA genes from each parent

• In clinical kidney transplantation, the HLA-A, B, and DR antigens are regarded as important

• The remarkable degree of polymorphism of these antigens accounts for the great difficulty in tissue matching

• Inherited in a Mendelian codominant way

Inheritance of HLA antigens

Mother FatherA B DR A B DR2 44 4 3 13 51 8 3 29 44 7

Sibling 1A B DR2 44 43 13 5

Sibling 2A B DR2 44 429 44 7

Sibling 3A B DR1 8 33 13 5

Sibling 4A B DR1 8 329 44 7

INHERITANCE OF HLA ANTIGENS

• Statistically there is 25% chance that the siblings will share the same parental haplotypes ( 2 haplotype match)

• 50% chance that they will share one haplotype

• 25% chance that neither haplotype will be the same (zero haplotype match)

RECIPIENT EVALUATION

• Check for antibodies against VZV, CMV, HBV, HCV, HIV

• Check for strongyloides infection or schistosomiasis

• Patients blood group because recipient must receive a transplant from a blood group compatible donor, Rh factor not needed

RECIPIENT EVALUATION• Panel reactive antibodies (PRA) done by

monthly screening of recipients serum; > 50% patient is highly sensitized. Also important to define the antigens to which recipient is sensitized

PregnancyBlood transfusionsPrevious failed kidney transplant

• White cell cross match: Mix donor white cells with recipients serum & complement. A positive cross- match is a contraindication to transplant

DONOR EVALUATION

• Not hypertensive• Diabetic• normal renal function • No infections; HIV, HBV, HCV• Psychiatric evaluation: psychologically sound,

no coercion• Lab: CBC, FBS,LFT, Urine analysis, MC&S,

assess GFR, CXR, ECG, HLA screening, viral screening, tuberculin skin test, IVU, renal angiogram

Phases of immunosuppression

• Induction immunosuppression: requires use of powerful drugs that are specific for cells that initiate & effect allograft directed immune response

Antibodies ALG, ATGAM, OKT3, IL-2 receptor Abs

• Maintenance immunosuppression: steroids, CNI, adjunctive agents AZT, MMF

• Treatment of acute rejection: Abs, pulsed methyl prednisolone

KIDNEY DIALYSIS AND TRANSPLANTPROS AND CONS

PROS CONS

RENALTRANSPLANT

• Can be done prior to start of dialysis

• Improved health with more active lifestyle

• No longer need dialysis• Higher long term

survival rate

• Psychological stress of having a family member involved

• Time involved for evaluation and testing process

• May be responsible for travel expenses, wages lost

PROS CONSHAEMODIALYSIS • Patient gets to know

other dialysis patients

• Frequent access to health care team

• Fistula or AV graft surgically inserted

• May have to travel to a center

• Disrupts work schedule due to fixed schedule

• Less privacy (Sleep with other patients for nocturnal)

• More ups and downs in clinical condition

• Must maintain a strict diet and fluid restriction

• Must follow center’s rules regarding food, visitors etc

Longer Life with a Transplant•Patients who receive a kidney transplant typically live longer than those who stay on dialysis.

•A living donor kidney functions, on average, 12 to 20 years, and a deceased donor kidney from 8 to 12 years.

•Patients who get a kidney transplant before dialysis live an average of 10 to 15 years longer than if they stayed on dialysis.

• Younger adults benefit the most from a kidney transplant, but even adults as old as 75 gain an average of four more years after a transplant than if they had stayed on dialysis.

• Average relative risk of death after renal transplantation in the time periods 0 to 30 d, 31 to 365 d, and greater than 365 d in Ontario.

Data from US Renal Data System. USRD 2003 annual data report: atlas of end stage renal disease in the United States.

Effect of HLA-A, -B, -DR Mismatching on Kidney Graft Survival

The economics of kidney transplantation versus hemodialysis•Using 1998 data for 8 transplantation centers located in New York City, this study found that kidney transplantation was a more cost-effective treatment than dialysis. •The initially higher costs of transplantation were fully recouped 2 years and 10 months after surgery.•Transplantation will also generate average monthly savings of $3800 over dialysis for the 2 years following the break-even point.

RECOMMENDATIONS FOR INCREASING DONATION

Kidney donor selection and refusal criteria•The physical condition of the donor, especially of the organ to be donated, is more important than age. •Important risk factors for organ failure are a prolonged history of diabetes mellitus or serious hypertension with retinal vascular damage.•Factors for excluding potential donors include previous myocardial infarction, coronary bypass angina, severe systemic vascular disease and long-lasting hypotension, oliguria and a long period in intensive care.

• Different circumstances apply when a recipient is already infected with HIV or hepatitis and transplant from infectious donors is possible in certain situations.

• A previous history of malignancy is not usually a contraindication for organ donation. However, absolute contraindications are active cancer or a history of metastatic cancer (with a few exceptions, e.g. testicular cancer) and cancers with high recurrence rates, e.g. lymphoma.

CONCLUSION

Even though kidney transplant is a major surgery with a phased recovery period, it can, in comparison to dialysis, offer the opportunity for

a LONGER AND MORE SATISFYING LIFE.