renal transplantation

1. PEDIATRIC KIDNEY
TRANSPLANTATION

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.

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. Congenital nephrotic syndrome.
8. Chronic glomerulonephritis.

6. ABSOLUTECONTRAINDICATIONS
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 familyneed 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. RecipientSelection

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 (human leukocyte antigen) class I and class II
antigens.

10. TissueTyping
• HLA antigens are the major transplantation
antigens, located on the short arm of ch 6.
• 2 classes of HLA antigens.
• Class I HLA
• Class II HLA

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. CardiovascularAssessment
• Nuclear medicine myocardial perfusion
imaging (MIBI) with exercise.
• ECG.
• Echocardiography with exercise.
• Echocardiography with dobutamine.

15. BladderAssessment
•VCUG.
•Urodynamic studies.

16. VascularAssessment
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 LivingDonor
• 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 LivingDonor?
• 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 ofDeceased
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. RoutineInvestigations
• 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 SurgicalPreparation
• 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 preservethekidney?
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 ofImmunosuppression
•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-thymocyteGlobulin
• 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 ReceptorBlockers
• 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. CalcineurinInhibitors
• 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 SignalsInhibitors
• 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 TransplantationComplications
1. Surgical complications.
2. Delayed graft function.
3. Lymphocele.
4. Acute rejection.
5. Infectious complications.
6. Malignancy.
7. Chronic allograft
dysfunction.

43. SurgicalComplications
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 GraftFunction
• 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. AcuteRejection
• 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 AllograftDysfunction
• 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 DoGrafts Fail?
1. Chronic rejection.
2. Acute rejection.
3. Vascular thrombosis.
4. Recurrent disease.
5. Non adherence to the
treatment.

58. ROUTINE POST-OPERATIVEREGIMEN
• 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.