Pediatric and Adult Transplantation

1. Pediatric and AdultTransplantation • ORGANS Heart Lung (single or double) Heart & Lung Kidney Pancreas Kidney & Pancreas Intestine • TISSUES Bone Marrow Stem Cell Cornea Heart valves Tendons Skin Bone

2. The Numbers - Completed http://www.unos.org

3. The Numbers http://www.unos.org

4. The Numbers – By Organ ORGAN Heart Lung (single or double) Heart & Lung Kidney Pancreas Kidney & Pancreas Liver Feb 2006 38,878 13,866 903 218,381 4,813 13,309 75,532 http://www.unos.org

5. The Numbers – Still Waiting As of ORGAN Heart Lung (single or double) Heart & Lung Kidney Pancreas Kidney & Pancreas Liver Feb 2006 3,023 3,122 150 69,752 1,772 2,585 17,734 http://www.unos.org

6. The Numbers – The Wait Days 206+22 704+30 889+120 1099+30 179+35 442+35 517+35 ORGAN Heart Lung (single or double) Heart & Lung Kidney Pancreas Kidney & Pancreas Liver http://www.optn.org

7. The Numbers – Die Waiting This yr. 2/16/04 465 386 15 2,980 28 181 1,506 ORGAN Heart Lung (single or double) Heart & Lung Kidney Pancreas Kidney & Pancreas Liver 51,179DEATHS awaiting ’95-’04 http://www.optn.org

8. Survival Rates (%) http://www.optn.org

9. Organ Shortage • less than half of the nation's donor pool is being utilized • rate of organ donation varies: age, racial, and demographic groups - the family of a donor <50 years old is 5x more likely to consent to organ donation than a family of a donor >60 years old - African Americans donate organs half as frequently as Caucasians (Asians, Hispanic) • differences attributed to several factors: - way families are approached and informed about organ donation clergy members or social workers are involved in these discussions, higher donation rates - distrust of the organ donation system

10. Indiana Donor Choice Law • supports your donation decision – legal directive • Previously, family consent was required for organ donation • Now, if 18+ and have signed driver's license, donor card, or other legal document indicating that you want to be a donor, qualified medical personnel have the legal authority to carry out your last wish • <18yrs old, can still be a donor, but parents or guardian will be asked for consent *House Enrolled Act 1628, Amended IC 29-2-16-2.5, effective July, 2001.

11. Cadaver Donor Process • UNOS maintains a centralized computer network linking all organ procurement organizations & transplant centers. • When a deceased organ donor is identified, a transplant coordinator from an organ procurement organization accesses UNOS system • Each patient in the "pool" is matched by the computer against the donor characteristics • A ranked list of patients for each organ that is procured from that donor is generated • Factors affecting ranking: tissue match, blood type, length of time on the waiting list, immune status and the distance between the potential recipient and the donor • The organ is offered to the transplant team of the first person on the list: Often, top patient will not get the organ: must be compatible with donor, must be healthy enough to undergo major surgery, and willing to be transplanted immediately. http://www.unos.org

12. Live Donation Living donor transplants are a viable alternative for patients in need of new organs: • 1954, 23-yr-old identical twins - ktx - Donor went on to live an active, normal life, died from causes unrelated to the transplant • Related: parents, children, siblings, and other relatives donate to family members • Unrelated donors (ie. spouses or close friends) may also donate their organs if a match • Living "stranger-to-stranger" donation is new & growing source of donors – ethics? http://www.unos.org

13. Organ Types for Living Donation • Single kidney most frequent type of living organ donation • Liver donate segments of the liver- ability to regenerates & regains full function • Lung donate lobes of the lung- lung lobes do not regenerate • Pancreas donate a portion of the pancreas - the pancreas does not regenerate, but usually no problems w/ reduced function ------------------------------- • Domino transplant http://www.unos.org

14. Qualifications for Living Donors • physically fit, in good general health, & free from high blood pressure, diabetes, cancer, kidney disease, and heart disease • usually 18-60 yrs of age • gender & race are not factors in determining a successful match • living donor must first undergo a blood test to determine blood type compatibility with the recipient. Blood Type Compatibility Chart RecipientDonor O = O A = A or O B = B or O AB = A, B, AB, or O http://www.unos.org

15. Qualifications for Living Donors • Medical history & physical examination • Tissue Typing:blood draw for tissue typing of the WBCs • Crossmatching: blood test to check if react to the donor organ "positive," = incompatible, "negative" tx proceeds routinely performed for kidney and pancreas transplants • Antibody Screen: Donor’s WBCs and recipient’s serum are mixed to see if there are antibodies in the recipient that react with the antigens of the donor • Urine Tests: kidney donation, urine samples are collected for 24 hours to assess the donor's kidney function • X-rays & ECG: screen the donor for heart and lung disease • Arteriogram: screen for CVD • Psychiatric and/or psychological evaluation: donor & recip. http://www.unos.org

21. Kidney Transplant

22. Kidney • Donor kidney ureter is attached directly to the bladder & is connected to the recipient's blood vessels

23. Lung Transplant Lung - uni/bilateral C under armpit - remove rib/s

24. Lung • Orthotopic - single, double or heart-lung • living-donor lobar lung tx -extends lives for double-lung or heart-lung tx -lower lobe of one lung (2 living donors -related or not) transplanted into the recipient -complex & performed rarely

25. Heart Transplant

26. Heart Transplant

27. Orthotopic vs Heterotopic Heterotopic -"backup battery“ • recipient’s heart not removed -chambers & blood vessels of both hearts • very rarely used (d-heart need extra help to fx in recipient) -recipient’s body > donor's -donor's heart functions poorly -pulmonary hypertension Heart - Orthotopic • blood flow diverted from heart to heart-lung bypass machine & heart stopped with chemical solution • front part of heart cut away & back walls of left & right atria stay • donor heart (minus its back walls) grafted into remaining part heart

28. Pancreas Transplant

29. Pancreas (PA/SPK) • diseased pancreas & the duodenum not removed • donor pancreas & duodenum inserted in right lower portion of patient's abdomen & attached to their blood vessels and intestine Islet Transplantation • local anaesthetic & 60 mins. -islets injected into liver & secrete insulin directly into circulatory system to control blood sugars.

30. Liver Transplant

31. Liver - orthotopic • Removal of the patient's liver, leaving portions of major blood vessels in place • donor liver will then be inserted and attached to these blood vessels and to the patient's bile ducts Heterotopic – • provides an auxiliary liver – fewer technical difficulties • won't need lifetime immunosuppressant therapy • worst-case scenario, liver doesn't come back & donor liver functions in its place just like a regular transplant • results discouraging rarely used Liver – live donation

32. Medical/Surgical Concerns • Primary non-function (early) • Bleeding, thrombosis (early) • Infection - bacterial, viral, fungal • Wound infections • Medication toxicities • Rejection • Anastomotic leaks • Other: electrolyte imbalance • Immunosuppressive side effects - Diabetes - Hypertension - Hyperlipidemia - Increased bone resorption (osteoporosis)

33. Organ SpecificMed/Surg Concerns Liver • Biliary leaks, strictures, obstructions • Vascular problems: HAT, HVT • Ascites • Recurrent Disease (HBV, HCV) • Malignanacies - imaging, labs

34. Organ SpecificMed/Surg Concerns Kidney/Pancreas • delayed graft function • kidney imaging: renal scan, renal arteriogram Heart • echo for left ventricular function (global graft atherosclerosis) Lung • bronchoscopy • PFTs (FVC, FEV1, F25/75)

35. Rejection • Fever or not • Tenderness or not • Elevated labs (CBC & organ specific) • Biopsy

37. Rejection Liver – fever, ↑ labs, bx Transaminase aspartate aminotransferase (AST) alanine aminotransferease (ALT) -elevation reflects hepatocyte injury • Cholestatic enzymes alkaline phosphatase (ALK), bilirubin (tot. bili) -reflect secretion of bile • Coagulopathy prothrombin time (PT)

38. Rejection Kidney- tenderness, acidic urine and/or ↓urine output, labs, bx • Blood urea nitrogen (BUN) waste product excreted by kidney – elevated with rejection but can be skewed by high protein intake • Creatinine (Cr) waste product excreted by kidney – elevated with rejection, dehydration, and with elevated levels of drugs that are toxic to kidney • Electrolytes potassium, sodium, chloride, bicarbonate, calcium, phosphorus

39. Rejection Heart • reduced exercise tolerance and/or SOB • transjugular biopsy • echo for left ventricular function (global graft atherosclerosis) • Labs: CBC (WBC) Lung • dyspnea • bronchoscopy with biopsy • PFTs (FVC, FEV1, F25/75) • Labs: CBC (WBC

40. Post Transplant Medications For Side Effects: • Antihypertensives • Antihyperlipidemics • Glucose regulators • Antiosteoporotics • Antidepressants For Transplant: • Immunosuppressants • Antifungals • Antivirals • Antibiotics • Anti ulcers • Digestant PLUSother medications for pre-existing conditions

41. Current Immunosuppressants • cyclosporin(ie.) Sandimmune, Neoral, Gengraf - inhibit cytokine synthesis & release – early t-cell activation tacrolimus (ie.) Prograf - 10-200x more potent than cyclosporin – same mechanism • azathioprine(ie.) Imuran - inhibits lymphocyte proliferation • mycophenolate mofetil (ie.) Cellcept - inhibits lymphocyte (T & B cells) proliferation – more specific,<toxicity • sirolimus (ie.) Rapamune -inhibits cytokine signaling transduction – late t-cell act. & maturation • corticosteroid(ie.)prednisone

42. Newest Immunosuppressants • daclizumab (ie.) Zenapax - monoclonal antibodies that inhibit antigen recognition • basiliximab (ie.) Simulect - monoclonal for injection only • anti-thymocyte globulin (rabbit) (ie.) Thymoglobulin -polyclonal antibodies that inhibit antigen recognition • muromonab –CD3 (ie.) OKT3 • - monoclonal, depletes blood of CD3+ t-cells • - leads to restoration of allograft function

43. Exercise for the Organ Transplant Recipient

44. Peak Oxygen Uptakes in Adult PRE Transplant Recipients VO2 (ml/kg/min) Heart & Lung Kidney D-Lung Liver Age-Pred. 40-49yo Heart

45. Improvements with Transplantation

46. Reasons for low functioning following transplantation • Residual effects of pre-transplant disease • Physical deconditioning / bedrest • Maintenance of sedentary behavior following transplant Transplant Rehab Intervention Project

47. 1996 U.S. Transplant Games Fitness Testing N = 128 • 76 kidney • 16 liver • 19 heart • 6 lung ( 4 single; 2 double) • 8 kidney/pancreas ( 1 pancreas only) • 4 bone marrow Painter, Transplantation. 64 (12): 1795, 1997

48. Transplant Games:cardiorespiratoryfitness 50 150 40 100 30 20 50 10 0 0 active inactive p=.000 p=.0001 Peak VO2 (ml/kg/min) % age-predicted VO2 Painter, Transplantation. 64 (12): 1795, 1997

49. Transplant Games: body composition 40 40 30 30 20 20 10 10 0 0 active inactive p=.02 p=.05 Skinfold % fat BMI Painter, Transplantation. 64 (12): 1795, 1997

50. 120 active p=.05 inactive 100 p=.08 p=.07 p=.05 p=.03 80 Scale Scores 60 40 20 0 PF BP GH RP VT SF RE MH Transplant Games Survey: SF-36 Scales Scores Painter, Transplantation. 64 (12): 1795, 1997