Transplant 101 Transplant 101: Overview

Transplant 101

Transplant 101: Overview

• Transplant as treatment for ESRD• The pretransplant evaluation

– Contraindications to transplantation

• Deciding on a donor– Deceased

• United Network for Organ Sharing (UNOS) and organ allocation

– Living• Determining a suitable candidate• Donor evaluation• Matching donor and recipient

History of Kidney Transplantation

• Initial experiments date back to World War II• AZA debuted in 1960s

– Transplant outcomes improved

• CsA introduced in the early 1980s– 1-year graft survival rate exceeds 80%

• Now, transplant patients have survival advantages over those remaining on dialysis

Treatment Modalities for ESRD Patients (2002)

28%

65%

6%

Transplantation

Hemodialysis

Peritonealdialysis

N = 431,284

USRDS 2004 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. 2004.

Transplant-Related Quality-of-Life Benefits

• Relatively unrestricted diet• Freedom to travel• Ability to become pregnant and bear

children• Can engage in training for athletic

competition• Lifestyle free of dialysis constraints

ESRD Survival by Treatment Modality

77.8%

93.7% 97.6%

62.9%

91.6%96.4%

31.9%

80.6%90.4%

9.0%

58.9%

77.8%

0%

20%

40%

60%

80%

100%

120%

Dialysis (post day91 of ESRD)

Posttransplantsurvival (deceased

donor)

Posttransplantsurvival (living

donor)

1 yr 2 yrs 5 yrs 10 yrs

National Kidney Foundation. Available at: http://www.kidney.org.

Treatment Modality in ESRD Patients Alive Beyond 10 Years

3%

28%

69%

Transplantation

Hemodialysis

Peritonealdialysis

USRDS 2000 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. 2000.

Graft Survival in 2405 Paired-Kidney Transplants: Short vs Long ESRD Time

Adapted with permission from Meier-Kriesche HU, et al. Transplantation. 2002;74:1377-1381.

Survival Benefit of Transplant vs Remaining on Waiting List

Adapted with permission from Ojo AO, et al. J Am Soc Nephrol. 2001;12:589-597.

Contraindications to Transplantation

• Active malignancy or metastatic cancer– Immunosuppression can enable tumor growth

• Cirrhosis– Unless simultaneous liver transplant is planned

• Severe myocardial dysfunction or peripheral vascular disease– Unless due to potentially reversible ischemia,

which should be corrected prior to transplant

• Other severe, irreversible extrarenal disease• Active mental illness

– If patient cannot give informed consent or comply with drug regimens

Kasiske BL, et al. Am J Transplant. 2001;1 (suppl 2):1-15.

Contraindications to Transplantation (cont’d)

• Chronic infection or untreated current infection• Irreversible limited rehabilitative potential• Persistent nonadherence to treatment• Active substance abuse

– Must be treated prior to transplant; drug screening may be required as proof of drug-free status

• Primary oxalosis– Unless combined liver/kidney transplant is an option


Referring Patients to the Transplant Center

• The referring nephrologist is responsible for coordinating all pretransplant care– Point person in coordinating care with

transplant center, specialists (eg, cardiology)

• Encouraging patients to learn about transplantation helps improve outcomes

• Transplantation can be preemptive– Identify potential donors

• Patient can be listed when GFR <20 mL/min

Kidney Transplant Evaluation ProcessReferred for transplant

Initial information session

Still a candidate?

Potential barrier?

Evaluate

Barrier removed?

Proceed with evaluation

Dialysis when indicated

No

No

Yes

Yes

No

Adapted with permission from Kasiske BL, et al. Am J Transplant. 2001;1 (suppl 2):1-95.

Pretransplant Recipient Evaluation

• Full medical history and physical exam

• CBC and chemistry panel

• PT and PTT• Blood type• HBV and HBC

serology• HIV screen

• CMV test• Pelvic exam and

Pap smear• Chest X-ray• ECG• HLA tissue typing

and cytotoxic antibodies

• VDRL screen

Routine tests


Pretransplant Recipient Evaluation

• Voiding cystourethrogram

• Pharmacologic or exercise stress test

• ECG• Coronary angiogram• Mammogram• Noninvasive vascular

study• Abdominal ultrasound• Upper GI series and

upper endoscopy

• Barium enema and lower endoscopy

• PSA test• Immunoelectrophoresis• EBV screen• VZV test• HSV titer• Toxoplasmosis titer• Lipid profile• PPD tuberculin test

Elective tests

Siddqi N, et al. In: Danovitch GM, ed. Handbook of Kidney Transplantation. 2005:169-192.

Reasons for Exclusion From Transplant Eligibility

46%

25%

10%

6%

5%8%

Medicalcontraindication

Patient declined

Obesity

Death

Insurance/financial

Unknown/unspecified

Holley JL, et al. Am J Kidney Dis. 1998;32:567-574.

Conditions Requiring Therapy Prior to Transplantation

• Active infection– Hepatitis– Diabetic foot infections– Tuberculosis

• Cardiovascular disease– Angiography and revascularization as

necessary

• Peptic ulcer disease• Cerebrovascular disease• Substance abuse


Malignancy and Transplantation• Standard waiting time is 2 years for most

cancers• Liver cancer—kidney transplant not

recommended without liver transplant• Multiple myeloma—transplant not

recommended• 2- to 5-year wait recommended

– Malignant melanoma (2 years if in situ)– Breast cancer – Cervical/uterine cancer (longer wait may reduce

recurrence)

Siddqi N, et al. In: Danovitch GM, ed. Handbook of Kidney Transplantation. 2005:169-192. Kiberd BA, et al. Am J Transplant. 2003;3:619-625.

Advantages and Disadvantages of Living-Donor Transplantation

Advantages Disadvantages

• Preemptive transplant option

• Can select donor for haplotype match, age

• Better outcomes

• Minimal delayed graft function

• No wait for deceased-donor kidney

• Can time transplant for convenience

• Immunosuppressive regimen may be less aggressive

• Emotional gain to donor

• Psychological stress to donor

• Long donor evaluation process

• Operative donor mortality (~1/3000 patients)

• Major complications (0.2%-2%)

• Minor complications (~50%)

• Potential donor hypertension, proteinuria

• Risk of trauma to remaining kidney

• Risk of unrecognized covert renal disease

Kendrick E, et al. In: Danovitch GM, ed. Handbook of Kidney Transplantation. 2005:135-168.

Living and Deceased Kidney Donors, 1993-2002

0

1000

2000

3000

4000

5000

6000

1993 1994 1995 1996 1997 1998 1999 2000 2001 2002

Tra

nsp

lan

ts,

No

.

Deceased donor Living donor

Year

2003 Annual Report of the United States OPTN/SRTR: Transplant Data 1993-2002.

Living Donor Evaluation

• Donor’s risk must be considered separately from recipient’s need for transplant

• Donor must be informed of the risks • ABO blood-type compatibility, tissue type, and

crossmatch are initial screening steps• With multiple suitable donors, the transplant

center will help determine the best donor – For a younger recipient who may require a second

transplant, a parent may be selected over a sibling, whose kidney may be needed in the future

Living Donor Evaluation (cont’d)• Medical history and physical exam• Comprehensive lab screening

– Blood count/chemistry panel– HBV, HCV, HIV, and CMV tests– Glucose tolerance test

• Urinalysis – 24-hour protein and creatinine

• Cardiovascular workup– Chest X-ray– ECG– Exercise treadmill for donors older than age 50

• Helical CT urogram• Psychosocial evaluation• Repeat crossmatch before transplant

Contraindications to Kidney Donation

• Age – <18 years or >65-70 years

• Hypertension – >140/90 mm Hg or need

for medication

• Diabetes

• Proteinuria – >250 mg/24 hours

• GFR <80 mL/min

• Microscopic hematuria

• Multiple renal vessels • Significant medical

illness• History of thrombosis or

thromboembolism• Strong family history of

renal disease, diabetes, or hypertension

• Psychiatric conditions or substance abuse

• Pregnancy

Kasiske BL, et al. J Am Soc Nephrol. 1996;7:2288-2313.

Donor/Recipient Matching

• Three factors are involved in tissue matching and antibody production– Human leukocyte antigen (HLA) antibodies– Crossmatch– Panel-reactive antibody (PRA)

HLA Matching

• Three groups of HLA proteins (HLA-A, HLA-B, HLA-DR)– Many different specific HLA proteins in each

group, each with a numerical designation

• One HLA in each group (haplotype) is inherited from each parent– 4 different combinations from 2 parents– 25% chance of siblings being haploidentical– 25% chance of siblings sharing no haplotype– 50% chance of siblings sharing 1 haplotype

Crossmatch

• Crossmatch tests whether the recipient has antibodies to the potential donor– Negative crossmatch is desired– Positive crossmatch increases risk of rejection– Antibodies can develop, so repeat crossmatch

testing is required immediately before transplant

Panel-Reactive Antibody (PRA)

• PRA is the amount of HLA antibody present in the recipient’s serum (expressed as a percentage)– Determined by testing the recipient’s serum

against a panel of cells from 60 people with different HLA proteins

– HLA antibodies can change, especially in response to blood transfusion, prior transplant, or pregnancy

– Higher % PRA makes finding a donor more difficult

Open Nephrectomy

• Advantages– Long-term safety

record– Simpler equipment

requirements– Minimal potential

abdominal complications

– Shorter operative time– Minimal warm ischemia

time– Excellent early graft

function

• Disadvantages– Postoperative pain– Recovery time prior to

return to work (6-8 weeks)

– Long surgical scar with potential for hernia

– Abdominal wall asymmetry possible


Laparoscopic Nephrectomy

• Advantages– Less postoperative

pain– Minimal surgical

scarring– Rapid return to work

(~4 weeks)– Shorter hospital stay– Magnified view of renal

vessels

• Disadvantages– Impaired early graft

function– Pneumoperitoneum may

compromise renal blood flow

– Longer operative time– Tendency to have shorter

renal vessels and multiple arteries

– Graft loss/damage during “learning curve”

– Added expense– Slight increase in donor

mortality


Waiting List for a Deceased-Donor Kidney

• When a living donor cannot be identified• Wait can exceed 5 years for blood

types O and B • Administered by UNOS

– Patient can be listed when GFR <20 mL/min– Transplant center will list the patient after

evaluation

• Patients should ask the transplant center if their names are on the list

Deceased-Donor Kidney AllocationUNOS allocates kidneys in this order:• Perfect HLA match, national basis• Locally, within recovering hospital’s OPO• To patients with PRA >80%

– In “payback” OPOs, then regionally, then nationally

• To patients age <18 years– In payback OPOs, then regionally, then nationally

• To patients with PRA 21% to 79%– In payback OPOs, then regionally, then nationally

• To patients with PRA 0% to 20%– In payback OPOs, then regionally, then nationally

• Within above categories, per points system

United Network for Organ Sharing. Available at: http://www.unos.org.

Accruing Points on the UNOS List

Points are awarded in accordance with this formula:• Time on waiting list• Quality of antigen mismatch—HLA-DR antigens

only (no points for HLA-A or HLA-B matches)• PRA—points are assigned if PRA level is >80% with

a negative preliminary donor/patient crossmatch• Pediatric patients (age <18) awarded add’l points• Donation status—individuals who have donated a

vital organ in the US receive preference• Medical urgency NOT a factor in points system

except by local agreement

United Network for Organ Sharing. Available at: http://www.unos.org.

Interim Medical Examinations

• During wait for a deceased-donor, routine medical evaluations should be conducted– Lipid panels– Diabetes screening– Cancer screening

• Pap smears and mammograms for women• Digital rectal exam or PSA test for men

– Cardiovascular examination as indicated

• The community nephrologist should advise the transplant center of changes in health that preclude transplantation

• Patients who require medical intervention may remain on the UNOS list, but do not accrue “time of waiting” points

Expanded-Criteria Donor (ECD) Kidneys

• From “marginal” donors whose age (>50 years) or medical status would once have precluded donation

• More likely to fail, but make transplantation more widely available

• ~15% of deceased-donor kidneys are ECD• Offered only to patients who consent in

advance to accept ECD organs

Accepting an ECD Kidney

• Decision: present benefits of ECD kidney vs future “standard” kidney

• ECD kidneys more attractive due to:– Increasing waiting times for standard kidneys– Aging donor population, increasing ECD

availability– Clinical improvements may narrow gap

between ECD and standard kidney outcomes

• Placement on ECD waiting list does not preclude eligibility for standard kidney

Schnitzler MA, et al. Transplantation. 2003;75:1940-1945.

Conclusion• Community nephrologists play a key role

in the transplant process– Identification of patients who will benefit from

transplant– Referral to the transplant center– Coordination of specialists in pretransplant

evaluation– Continuation of care while waiting for

transplant• Notifying transplant center of health status changes

– Long-term care posttransplant

Documents

Transplant 101 Transplant 101: Overview