kidney transplantation in pediatrics ahmed oshiba pediatric surgery and urology alexandria university

1. PEDIATRIC KIDNEY
TRANSPLANTATION
Ahmed Oshiba
Assistant Lecturer
Pediatric Surgery and Urology Department
Alexandria University

2. Dr. Emerich Ullmann
(1861-1937)
• Performed the first
experimental transplant in a
dog.
• He was able to
autotransplant a kidney
from its normal position to
the vessels of the neck in
March 1902.

3. HISTORY
• 1902: First experimental kidney
transplantation by Emerich Ullmann.
• 1933: First human kidney transplant by
Voronoy.
• 1950-53: First functioning human kidney
transplant.
• 1961: Azathioprine first used successfully.
• 1962: First use of tissue matching to select a
donor
• 1963: Prednisolone and Azathioprine
combination produced longer graft survival.
• 1972: Successful transplantation into a 9
month-old girl.
• 1978: First clinical use of cyclosporine A

4. Who Qualifies ?
• Progressive, irreversible
renal disease.
• No active malignancy or
infection.
• Absence of systemic
disease.
• Effective family or social
support systems.
• Good compliance.

5. INDICATIONS
1. Focal segmental glomerulosclerosis.
2. Obstructive uropathy.
3. Polycystic kidney disease.
4. Renal aplasia, hypoplasia, dysplasia.
5. Ig A nephropathy.
6. Hemolytic uremic syndrome.
7. Prune belly syndrome.
8. Congenital nephrotic syndrome.
9. Chronic glomerulonephritis.

6. ABSOLUTE CONTRAINDICATIONS
1. Active malignancy.
2. Severe respiratory conditions.
3. Severe Ischemic heart disease.
4. Severe peripheral vascular
disease.
5. Severe cognitive impairment.
6. Active drug or alcohol
addiction.
7. Patient non-adherence to
therapy.

7. What the family need to know?
• Transplant process.
• Program options.
• Risks and benefits.
• Medication regimen.
• Lifestyle adjustments.
• Effect of transplantation on
existing medical conditions.
• Short and long term outcomes.

8. Recipient Selection

9. • Must have established ESRD.
• Recipient should have a life expectancy > 5 years.
• No evidence of active infection.
• No evidence of active malignant disease.
• Psychiatric evaluation.
• Absolute Contraindications:
1. Presence of potentially harmful antibodies against the donor kidney.
2. Antibodies against the ABO blood group antigens.
3. Antibodies against HLA class I and class II antigens.

10. Tissue Typing
• HLA antigens are the major
transplantation antigens, located on the short
arm of ch 6.
• 2 classes of HLA antigens.
• Class I HLA antigens (HLA – A, B, C), they are
target for cytotoxic T lymphocytes (CD8+).
• Class II HLA antigens (HLA DR) are restricted
to B cells, monocytes/ macrophages. They
are target for (CD4+).

11. • ABO computability: recipient must receive a transplant from a blood group
compatible donor.
• 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:
1. Pregnancy.
2. Blood transfusions.
3. Previous failed kidney transplant.

12. Recipient
Evaluation

13. RECIPIENT
ASSESMENT

14. Cardiovascular Assessment
• Nuclear medicine
myocardial perfusion
imaging (MIBI) with
exercise.
• ECG.
• Echocardiography with
exercise.
• Echocardiography with
dobutamine.

15. Bladder Assessment
• VCUG.
• Urodynamic
studies.

16. Vascular Assessment
CT angiography.
Doppler Ultrasound.
Iliac Angiography.

17. Immunizations
1. Hepatitis B
2. Meningococcal.
3. Pneumococcal.
4. Influenza.
5. MMR.
6. Varicella.

18. Donor Selection

19. Donor Selection
Living
donor.
Deceased
donor.
Paired
exchange.

20. Donor Evaluation

21. Criteria of Living Donor
• Not hypertensive.
• Not diabetic.
• Normal renal function.
• No infections; HIV, HBV, HCV.
• Psychiatric evaluation: psychologically sound.
• Lab: CBC, FBS,LFT, Urine analysis, assess GFR, CXR, ECG, HLA screening,
viral screening, tuberculin skin test, IVU, renal angiogram.

22. Why Living Donor?
• It provides the greatest chance of a
successful outcome, as the kidney is healthy
and may last longer than a kidney from a
deceased donor.
• Transplantation can be scheduled for the
most favorable time for the donor and thus
avoids the prolonged wait for a deceased
donor.
• It helps to alleviate the critical shortage of
deceased organs.

23. Discussion
1. Open discussion between the
donor and recipient.
2. The procedure, implications,
risks and benefits to the donor.
3. Help the donor to take the
decision.
4. Book the surgery.
5. Repeat the cross match before
the surgery.

24. Criteria of Deceased
Donor
• less than 70 years of age.
• Has no evidence of irreversible
renal dysfunction.
• Has no known risk factors for
transmission of disease to the
recipient.
• Has no known transmittable
disease or malignancy.

25. TRANSPLANT

26. Routine Investigations
• CBC and platelet count.
• PTT and INR.
• Blood group; crossmatch of 2-4 units packed red cells.
• Electrolytes.
• Urea, creatinine and uric acid.
• Albumin and total protein.
• AST, ALT or gamma GT and alkaline phosphatase.
• Transplant immunology (10 cc of clotted blood).
• Chest X-ray.
• 12-lead electrocardiogram.

27. Pre Surgical Preparation
• Dialysis if required.
• Surgical preparation.
• Notation of last mealtime.
• Explanation of procedure to patient; signing of surgical consent form by patient.
• Establishment of time of surgery.
• Intravenous access lines.
• Administration of prophylactic antibiotics: cefazolin, penicillin, clindamycin.

28. Operation
The renal allograft is placed extra-peritoneally in the right or left iliac fossa.
Vascular anastomosis are between the donor renal vessels and usually the
external iliac vessels of the recipient.
Urinary reconstruction is almost always via uretero-neocystostomy (donor
ureter to recipient bladder).
Initial function is enhanced by short cold ischemic times, short re-warm
(anastomosis) times, and intravascular volume repletion.

32. How to preserve the kidney?
1. Hypothermic perfusion techniques.
2. Normothermic preservation techniques.
3. Oxygen insufflation technique.
4. Cold preservation solution at 4°C:
• The Euro-Collins (EC) solution.
• University of Wisconsin (UW) solution.
• Histidine-Tryptophan-Ketoglutarate (HTK) solution.
• Celsior solution.

33. Immunosuppression

34. Phases of Immunosuppression
• Induction immunosuppression: requires use of powerful drugs that
are specific for cells that initiate & effect allograft directed immune
response like Antibodies ALG, ATGAM, OKT3, IL-2 receptor Abs.
• Maintenance immunosuppression: steroids, CNI, adjunctive agents
AZT, MMF.
• Treatment of acute rejection: Abs, pulsed methyl prednisolone,
Intravenous Immunoglobulin (IVIG), Rituximab.

35. Corticosteroids
• Used for induction, maintenance and treatment of rejection.
• Mechanism of action:
Inhibit function of dendritic cells.
Inhibit translocation to nucleus of NF-κB.
Suppress production of IL-1, IL-2, IL-3, IL-6, TNF-α, and γ-IFN.
• Component of >80% of transplant protocols.
• Given IV at high doses (250-500 mg/day) for induction or treatment of rejection.
• Tapered to maintenance dose of 5-10 mg/day in early post-transplant phase.

36. Anti-thymocyte Globulin
• Used for induction and treatment of rejection.
• Causes depletion of peripheral blood lymphocytes.
• Administered generally via central line for 3-10 days.
• Premedication required: acetaminophen, corticosteroids
and antihistamine.

37. IL-2 Receptor Blockers
• Basiliximab (Simulect®) and Daclizumab (Xenapax®).
• Block CD25 (IL-2 receptor) on activated T cells.
• Used for induction only.
• Almost no side effects, but also much less potent.

38. Calcineurin Inhibitors
• Used for maintenance immunosuppression.
• Two agents in clinical practice: Cyclosporine, Tacrolimus.
• Generics NOT clinically therapeutically equivalent.
• At present are key to maintenance immunosuppression and a
component of the majority of transplant protocols.
• Nephrotoxicity is the most common complication in this group.

39. Proliferation Signals Inhibitors
• A key regulatory kinase in cell division.
• Sirolimus is the only available mTOR inhibitor.
• Administered once daily, 24-hour trough levels monitored.

40. Antimetabolites
• Azathioprine (Imuran) is a purine analogue that is incorporated into
RNA and inhibits cell replication.
• A mainstay of transplantation for 30 years, it has largely been
replaced by the below drugs.
• Mycophenolate mofetil and enteric-coated mycophenolate sodium
are prodrugs of mycophenolic acid (MPA), an inhibitor of inosine
monophosphate dehydrogenase (IMPDH).

41. Rituximab
• Used in the treatment of antibody-mediated rejection.
• Monoclonal antibody directed at CD20 antigen on B lymphocytes.
• Causes rapid and sustained depletion of B lymphocytes.
• Adverse events: infusion reactions, and increased susceptibility to
infection.

42. Post Transplantation Complications
1. Surgical complications.
2. Delayed graft function.
3. Lymphocele.
4. Acute rejection.
5. Infectious complications.
6. Malignancy.
7. Chronic allograft dysfunction.

43. Surgical Complications
Vascular thrombosis:
• Caused by thrombosis of donor renal artery or vein.
• Usually happens in the first week.
• Diagnosed by ultrasound with doppler studies.
• Almost always requires retransplantation.
 Urine leak:
• Elevated creatinine.
• May or may not have abdominal pain.
• Diagnose with nuclear medicine scans (DTPA or
MAG3).
• Surgical repair and/or relief of obstruction

44. Delayed Graft Function
• Need for dialysis in the first week after transplantation.
• Causes:
1. ATN from prolonged cold ischemia.
2. Acute rejection.
3. Recurrent disease.
• Usually requires biopsy for diagnosis and management.

45. Lymphocele
• Collection of lymph caused by leakage from iliac lymphatics.
• Presents several weeks post-operatively.
• Symptoms:
1. Compression of kidney, ureter, bladder causing obstructive
uropathy and ARF.
2. Compression of iliac vessels leading to unilateral lower extremity
edema and DVT.
3. Abdominal mass.
• Treatment is peritoneal window for drainage via open or laparoscopy.

47. Acute Rejection
• May present with ARF or proteinuria.
• Occurs in about 20%.
• Diagnosis made by renal biopsy.
• Acute cellular rejection: treat with steroids or ATG based
on severity.
• Antibody-mediated rejection: may require steroids, ATG,
rituximab, IVIG or plasmapheresis based on severity and
setting.

49. Malignancy
• May be related to impaired immune surveillance as a
result of immunosuppression.
• Skin cancer most common: sun protection mandatory.
• Specific malignancies:
1. Kaposi sarcoma.
2. Post-transplant lymphoproliferative disorder (PTLD).

51. Chronic Allograft Dysfunction
• Persistent rise in serum creatinine and worsening GFR over weeks to
months.
• Histological counterpart is chronic allograft nephropathy (CAN):
Characterized by nonspecific interstitial fibrosis and
tubular atrophy.
• Usually irreversible and will lead to allograft failure and need for
dialysis or retransplantation.

53. Infections
• Bacterial infection:
Most common during the first four weeks post-transplant.
• Fungal infection: Oral candidiasis is the most common fungal
disease in the early post-transplant period.
• Viral infection:
Usually seen between 4 to 26 weeks after transplant, The
principal viral infections are:

54. 1. Herpes simplex (HSV) stomatitis: responds rapidly to acyclovir or valacyclovir therapy.
2. Cytomegalovirus (CMV) infection: is the most common viral infection, it is usually treated with
ganciclovir IV or oral.
3. Epstein-Barr virus infection: there is a spectrum of clinical disease ranging from sore throat
and fever to post transplant lymphoproliferative disease (PTLD).
4. BK Polyoma Virus (BKV): Asymptomatic viruria with BKV occurs in approximately 30% of
kidney transplant recipients. Viruria precedes viremia which precedes kidney invasion.

55. Why Do Grafts Fail?
1. Chronic rejection.
2. Acute rejection.
3. Vascular thrombosis.
4. Recurrent disease.
5. Non adherence to the treatment.

58. ROUTINE POST-OPERATIVE REGIMEN
• Clinical Examination:
1. Urine output, blood pressure, CVP and weight are monitored daily.
2. Daily lab investigations include: serum creatinine (SCr), and
calcineurin inhibitor (CNI) blood.
3. Prophylactic Antibiotic Treatment: is continued for 24 to 36 hours
following transplantation.

59. • Peritoneal Dialysis (PD) Catheter: As long as the peritoneal cavity is
not entered during surgery, peritoneal dialysis may be performed
post-transplant as needed.
• Wound Care: The patient's incision is managed according to standard
hospital protocols.