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Transplant 101 Transplant 101: Overview


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Transplant 101 Transplant 101: Overview

  1. 1. Transplant 101
  2. 2. Transplant 101: Overview <ul><li>Transplant as treatment for ESRD </li></ul><ul><li>The pretransplant evaluation </li></ul><ul><ul><li>Contraindications to transplantation </li></ul></ul><ul><li>Deciding on a donor </li></ul><ul><ul><li>Deceased </li></ul></ul><ul><ul><ul><li>United Network for Organ Sharing (UNOS) and organ allocation </li></ul></ul></ul><ul><ul><li>Living </li></ul></ul><ul><ul><ul><li>Determining a suitable candidate </li></ul></ul></ul><ul><ul><ul><li>Donor evaluation </li></ul></ul></ul><ul><ul><ul><li>Matching donor and recipient </li></ul></ul></ul>
  3. 3. History of Kidney Transplantation <ul><li>Initial experiments date back to World War II </li></ul><ul><li>AZA debuted in 1960s </li></ul><ul><ul><li>Transplant outcomes improved </li></ul></ul><ul><li>CsA introduced in the early 1980s </li></ul><ul><ul><li>1-year graft survival rate exceeds 80% </li></ul></ul><ul><li>Now, transplant patients have survival advantages over those remaining on dialysis </li></ul>
  4. 4. Treatment Modalities for ESRD Patients (2002) N = 431,284 USRDS 2004 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. 2004.
  5. 5. Transplant-Related Quality-of-Life Benefits <ul><li>Relatively unrestricted diet </li></ul><ul><li>Freedom to travel </li></ul><ul><li>Ability to become pregnant and bear children </li></ul><ul><li>Can engage in training for athletic competition </li></ul><ul><li>Lifestyle free of dialysis constraints </li></ul>
  6. 6. ESRD Survival by Treatment Modality National Kidney Foundation. Available at:
  7. 7. Treatment Modality in ESRD Patients Alive Beyond 10 Years USRDS 2000 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. 2000.
  8. 8. 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.
  9. 9. 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.
  10. 10. Contraindications to Transplantation <ul><li>Active malignancy or metastatic cancer </li></ul><ul><ul><li>Immunosuppression can enable tumor growth </li></ul></ul><ul><li>Cirrhosis </li></ul><ul><ul><li>Unless simultaneous liver transplant is planned </li></ul></ul><ul><li>Severe myocardial dysfunction or peripheral vascular disease </li></ul><ul><ul><li>Unless due to potentially reversible ischemia, which should be corrected prior to transplant </li></ul></ul><ul><li>Other severe, irreversible extrarenal disease </li></ul><ul><li>Active mental illness </li></ul><ul><ul><li>If patient cannot give informed consent or comply with drug regimens </li></ul></ul>Kasiske BL, et al. Am J Transplant. 2001;1 (suppl 2):1-15.
  11. 11. Contraindications to Transplantation (cont’d) <ul><li>Chronic infection or untreated current infection </li></ul><ul><li>Irreversible limited rehabilitative potential </li></ul><ul><li>Persistent nonadherence to treatment </li></ul><ul><li>Active substance abuse </li></ul><ul><ul><li>Must be treated prior to transplant; drug screening may be required as proof of drug-free status </li></ul></ul><ul><li>Primary oxalosis </li></ul><ul><ul><li>Unless combined liver/kidney transplant is an option </li></ul></ul>Kasiske BL, et al. Am J Transplant. 2001;1 (suppl 2):1-15.
  12. 12. Referring Patients to the Transplant Center <ul><li>The referring nephrologist is responsible for coordinating all pretransplant care </li></ul><ul><ul><li>Point person in coordinating care with transplant center, specialists (eg, cardiology) </li></ul></ul><ul><li>Encouraging patients to learn about transplantation helps improve outcomes </li></ul><ul><li>Transplantation can be preemptive </li></ul><ul><ul><li>Identify potential donors </li></ul></ul><ul><li>Patient can be listed when GFR <20 mL/min </li></ul>
  13. 13. Kidney Transplant Evaluation Process Referred 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.
  14. 14. Pretransplant Recipient Evaluation <ul><li>Full medical history and physical exam </li></ul><ul><li>CBC and chemistry panel </li></ul><ul><li>PT and PTT </li></ul><ul><li>Blood type </li></ul><ul><li>HBV and HBC serology </li></ul><ul><li>HIV screen </li></ul><ul><li>CMV test </li></ul><ul><li>Pelvic exam and Pap smear </li></ul><ul><li>Chest X-ray </li></ul><ul><li>ECG </li></ul><ul><li>HLA tissue typing and cytotoxic antibodies </li></ul><ul><li>VDRL screen </li></ul>Routine tests Kasiske BL, et al. Am J Transplant. 2001;1 (suppl 2):1-95.
  15. 15. Pretransplant Recipient Evaluation <ul><li>Voiding cystourethrogram </li></ul><ul><li>Pharmacologic or exercise stress test </li></ul><ul><li>ECG </li></ul><ul><li>Coronary angiogram </li></ul><ul><li>Mammogram </li></ul><ul><li>Noninvasive vascular study </li></ul><ul><li>Abdominal ultrasound </li></ul><ul><li>Upper GI series and upper endoscopy </li></ul><ul><li>Barium enema and lower endoscopy </li></ul><ul><li>PSA test </li></ul><ul><li>Immunoelectrophoresis </li></ul><ul><li>EBV screen </li></ul><ul><li>VZV test </li></ul><ul><li>HSV titer </li></ul><ul><li>Toxoplasmosis titer </li></ul><ul><li>Lipid profile </li></ul><ul><li>PPD tuberculin test </li></ul>Elective tests Siddqi N, et al. In: Danovitch GM, ed. Handbook of Kidney Transplantation. 2005:169-192.
  16. 16. Reasons for Exclusion From Transplant Eligibility Holley JL, et al. Am J Kidney Dis. 1998;32:567-574.
  17. 17. Conditions Requiring Therapy Prior to Transplantation <ul><li>Active infection </li></ul><ul><ul><li>Hepatitis </li></ul></ul><ul><ul><li>Diabetic foot infections </li></ul></ul><ul><ul><li>Tuberculosis </li></ul></ul><ul><li>Cardiovascular disease </li></ul><ul><ul><li>Angiography and revascularization as necessary </li></ul></ul><ul><li>Peptic ulcer disease </li></ul><ul><li>Cerebrovascular disease </li></ul><ul><li>Substance abuse </li></ul>Kasiske BL, et al. Am J Transplant. 2001;1 (suppl 2):1-95.
  18. 18. Malignancy and Transplantation <ul><li>Standard waiting time is 2 years for most cancers </li></ul><ul><li>Liver cancer —kidney transplant not recommended without liver transplant </li></ul><ul><li>Multiple myeloma — transplant not recommended </li></ul><ul><li>2- to 5-year wait recommended </li></ul><ul><ul><li>Malignant melanoma (2 years if in situ) </li></ul></ul><ul><ul><li>Breast cancer </li></ul></ul><ul><ul><li>Cervical/uterine cancer (longer wait may reduce recurrence) </li></ul></ul>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.
  19. 19. Advantages and Disadvantages of Living-Donor Transplantation Kendrick E, et al . In: Danovitch GM, ed. Handbook of Kidney Transplantation. 2005:135-168. <ul><li>Psychological stress to donor </li></ul><ul><li>Long donor evaluation process </li></ul><ul><li>Operative donor mortality (~1/3000 patients) </li></ul><ul><li>Major complications (0.2%-2%) </li></ul><ul><li>Minor complications (~50%) </li></ul><ul><li>Potential donor hypertension, proteinuria </li></ul><ul><li>Risk of trauma to remaining kidney </li></ul><ul><li>Risk of unrecognized covert renal disease </li></ul><ul><li>Preemptive transplant option </li></ul><ul><li>Can select donor for haplotype match, age </li></ul><ul><li>Better outcomes </li></ul><ul><li>Minimal delayed graft function </li></ul><ul><li>No wait for deceased-donor kidney </li></ul><ul><li>Can time transplant for convenience </li></ul><ul><li>Immunosuppressive regimen may be less aggressive </li></ul><ul><li>Emotional gain to donor </li></ul>Disadvantages Advantages
  20. 20. Living and Deceased Kidney Donors, 1993-2002 Year 2003 Annual Report of the United States OPTN/SRTR: Transplant Data 1993-2002 .
  21. 21. Living Donor Evaluation <ul><li>Donor’s risk must be considered separately from recipient’s need for transplant </li></ul><ul><li>Donor must be informed of the risks </li></ul><ul><li>ABO blood-type compatibility, tissue type, and crossmatch are initial screening steps </li></ul><ul><li>With multiple suitable donors, the transplant center will help determine the best donor </li></ul><ul><ul><li>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 </li></ul></ul>
  22. 22. Living Donor Evaluation (cont’d) <ul><li>Medical history and physical exam </li></ul><ul><li>Comprehensive lab screening </li></ul><ul><ul><li>Blood count/chemistry panel </li></ul></ul><ul><ul><li>HBV, HCV, HIV, and CMV tests </li></ul></ul><ul><ul><li>Glucose tolerance test </li></ul></ul><ul><li>Urinalysis </li></ul><ul><ul><li>24-hour protein and creatinine </li></ul></ul><ul><li>Cardiovascular workup </li></ul><ul><ul><li>Chest X-ray </li></ul></ul><ul><ul><li>ECG </li></ul></ul><ul><ul><li>Exercise treadmill for donors older than age 50 </li></ul></ul><ul><li>Helical CT urogram </li></ul><ul><li>Psychosocial evaluation </li></ul><ul><li>Repeat crossmatch before transplant </li></ul>
  23. 23. Contraindications to Kidney Donation <ul><li>Age </li></ul><ul><ul><li><18 years or >65-70 years </li></ul></ul><ul><li>Hypertension </li></ul><ul><ul><li>>140/90 mm Hg or need for medication </li></ul></ul><ul><li>Diabetes </li></ul><ul><li>Proteinuria </li></ul><ul><ul><li>>250 mg/24 hours </li></ul></ul><ul><li>GFR <80 mL/min </li></ul><ul><li>Microscopic hematuria </li></ul><ul><li>Multiple renal vessels </li></ul><ul><li>Significant medical illness </li></ul><ul><li>History of thrombosis or thromboembolism </li></ul><ul><li>Strong family history of renal disease, diabetes, or hypertension </li></ul><ul><li>Psychiatric conditions or substance abuse </li></ul><ul><li>Pregnancy </li></ul>Kasiske BL, et al. J Am Soc Nephrol. 1996;7:2288-2313.
  24. 24. Donor/Recipient Matching <ul><li>Three factors are involved in tissue matching and antibody production </li></ul><ul><ul><li>Human leukocyte antigen (HLA) antibodies </li></ul></ul><ul><ul><li>Crossmatch </li></ul></ul><ul><ul><li>Panel-reactive antibody (PRA) </li></ul></ul>
  25. 25. HLA Matching <ul><li>Three groups of HLA proteins (HLA-A, HLA-B, HLA-DR) </li></ul><ul><ul><li>Many different specific HLA proteins in each group, each with a numerical designation </li></ul></ul><ul><li>One HLA in each group (haplotype) is inherited from each parent </li></ul><ul><ul><li>4 different combinations from 2 parents </li></ul></ul><ul><ul><li>25% chance of siblings being haploidentical </li></ul></ul><ul><ul><li>25% chance of siblings sharing no haplotype </li></ul></ul><ul><ul><li>50% chance of siblings sharing 1 haplotype </li></ul></ul>
  26. 26. Crossmatch <ul><li>Crossmatch tests whether the recipient has antibodies to the potential donor </li></ul><ul><ul><li>Negative crossmatch is desired </li></ul></ul><ul><ul><li>Positive crossmatch increases risk of rejection </li></ul></ul><ul><ul><li>Antibodies can develop, so repeat crossmatch testing is required immediately before transplant </li></ul></ul>
  27. 27. Panel-Reactive Antibody (PRA) <ul><li>PRA is the amount of HLA antibody present in the recipient’s serum (expressed as a percentage) </li></ul><ul><ul><li>Determined by testing the recipient’s serum against a panel of cells from 60 people with different HLA proteins </li></ul></ul><ul><ul><li>HLA antibodies can change, especially in response to blood transfusion, prior transplant, or pregnancy </li></ul></ul><ul><ul><li>Higher % PRA makes finding a donor more difficult </li></ul></ul>
  28. 28. Open Nephrectomy <ul><li>Advantages </li></ul><ul><ul><li>Long-term safety record </li></ul></ul><ul><ul><li>Simpler equipment requirements </li></ul></ul><ul><ul><li>Minimal potential abdominal complications </li></ul></ul><ul><ul><li>Shorter operative time </li></ul></ul><ul><ul><li>Minimal warm ischemia time </li></ul></ul><ul><ul><li>Excellent early graft function </li></ul></ul><ul><li>Disadvantages </li></ul><ul><ul><li>Postoperative pain </li></ul></ul><ul><ul><li>Recovery time prior to return to work (6-8 weeks) </li></ul></ul><ul><ul><li>Long surgical scar with potential for hernia </li></ul></ul><ul><ul><li>Abdominal wall asymmetry possible </li></ul></ul>Kendrick E , et al. In: Danovitch GM, ed. Handbook of Kidney Transplantation. 2005:135-168.
  29. 29. Laparoscopic Nephrectomy <ul><li>Advantages </li></ul><ul><ul><li>Less postoperative pain </li></ul></ul><ul><ul><li>Minimal surgical scarring </li></ul></ul><ul><ul><li>Rapid return to work (~4 weeks) </li></ul></ul><ul><ul><li>Shorter hospital stay </li></ul></ul><ul><ul><li>Magnified view of renal vessels </li></ul></ul><ul><li>Disadvantages </li></ul><ul><ul><li>Impaired early graft function </li></ul></ul><ul><ul><li>Pneumoperitoneum may compromise renal blood flow </li></ul></ul><ul><ul><li>Longer operative time </li></ul></ul><ul><ul><li>Tendency to have shorter renal vessels and multiple arteries </li></ul></ul><ul><ul><li>Graft loss/damage during “learning curve” </li></ul></ul><ul><ul><li>Added expense </li></ul></ul><ul><ul><li>Slight increase in donor mortality </li></ul></ul>Kendrick E , et al. In: Danovitch GM, ed. Handbook of Kidney Transplantation. 2005:135-168.
  30. 30. Waiting List for a Deceased-Donor Kidney <ul><li>When a living donor cannot be identified </li></ul><ul><li>Wait can exceed 5 years for blood types O and B </li></ul><ul><li>Administered by UNOS </li></ul><ul><ul><li>Patient can be listed when GFR <20 mL/min </li></ul></ul><ul><ul><li>Transplant center will list the patient after evaluation </li></ul></ul><ul><li>Patients should ask the transplant center if their names are on the list </li></ul>
  31. 31. Deceased-Donor Kidney Allocation <ul><li>UNOS allocates kidneys in this order: </li></ul><ul><li>Perfect HLA match, national basis </li></ul><ul><li>Locally, within recovering hospital’s OPO </li></ul><ul><li>To patients with PRA > 80% </li></ul><ul><ul><li>In “payback” OPOs, then regionally, then nationally </li></ul></ul><ul><li>To patients age <18 years </li></ul><ul><ul><li>In payback OPOs, then regionally, then nationally </li></ul></ul><ul><li>To patients with PRA 21% to 79% </li></ul><ul><ul><li>In payback OPOs, then regionally, then nationally </li></ul></ul><ul><li>To patients with PRA 0% to 20% </li></ul><ul><ul><li>In payback OPOs, then regionally, then nationally </li></ul></ul><ul><li>Within above categories, per points system </li></ul>United Network for Organ Sharing. Available at:
  32. 32. Accruing Points on the UNOS List <ul><li>Points are awarded in accordance with this formula: </li></ul><ul><li>Time on waiting list </li></ul><ul><li>Quality of antigen mismatch — HLA-DR antigens only (no points for HLA-A or HLA-B matches) </li></ul><ul><li>PRA — points are assigned if PRA level is > 80% with a negative preliminary donor/patient crossmatch </li></ul><ul><li>Pediatric patients (age <18) awarded add’l points </li></ul><ul><li>Donation status — individuals who have donated a vital organ in the US receive preference </li></ul><ul><li>Medical urgency NOT a factor in points system except by local agreement </li></ul>United Network for Organ Sharing. Available at:
  33. 33. Interim Medical Examinations <ul><li>During wait for a deceased-donor, routine medical evaluations should be conducted </li></ul><ul><ul><li>Lipid panels </li></ul></ul><ul><ul><li>Diabetes screening </li></ul></ul><ul><ul><li>Cancer screening </li></ul></ul><ul><ul><ul><li>Pap smears and mammograms for women </li></ul></ul></ul><ul><ul><ul><li>Digital rectal exam or PSA test for men </li></ul></ul></ul><ul><ul><li>Cardiovascular examination as indicated </li></ul></ul><ul><li>The community nephrologist should advise the transplant center of changes in health that preclude transplantation </li></ul><ul><li>Patients who require medical intervention may remain on the UNOS list, but do not accrue “time of waiting” points </li></ul>
  34. 34. Expanded-Criteria Donor (ECD) Kidneys <ul><li>From “marginal” donors whose age (>50 years) or medical status would once have precluded donation </li></ul><ul><li>More likely to fail, but make transplantation more widely available </li></ul><ul><li>~15% of deceased-donor kidneys are ECD </li></ul><ul><li>Offered only to patients who consent in advance to accept ECD organs </li></ul>
  35. 35. Accepting an ECD Kidney <ul><li>Decision: present benefits of ECD kidney vs future “standard” kidney </li></ul><ul><li>ECD kidneys more attractive due to: </li></ul><ul><ul><li>Increasing waiting times for standard kidneys </li></ul></ul><ul><ul><li>Aging donor population, increasing ECD availability </li></ul></ul><ul><ul><li>Clinical improvements may narrow gap between ECD and standard kidney outcomes </li></ul></ul><ul><li>Placement on ECD waiting list does not preclude eligibility for standard kidney </li></ul>Schnitzler MA, et al. Transplantation. 2003;75:1940-1945.
  36. 36. Conclusion <ul><li>Community nephrologists play a key role in the transplant process </li></ul><ul><ul><li>Identification of patients who will benefit from transplant </li></ul></ul><ul><ul><li>Referral to the transplant center </li></ul></ul><ul><ul><li>Coordination of specialists in pretransplant evaluation </li></ul></ul><ul><ul><li>Continuation of care while waiting for transplant </li></ul></ul><ul><ul><ul><li>Notifying transplant center of health status changes </li></ul></ul></ul><ul><ul><li>Long-term care posttransplant </li></ul></ul>