RENAL TRANSPLANTATION

PROF DR MOHAMMED YOUSSIFPROF DR MOSTAFA SAEID

NAIM HAZIMI BIN YAHYA 10-5-240

Introduction & Indication

Introduction

• Kidney / renal transplantation is the organ transplant of a kidney into a patient with end-stage renal disease

• End-stage renal disease is the name for kidney failure so advanced it cannot be reversed

• Dialysis and kidney transplantation are the only treatments for this condition

Dialysis vs TransplantCriteria Dialysis Transplant

Life expectency 5+/- years Up to 20 years

Cost Cheap, but require lifelong Expensive, one time

QOL Not good Better than dialysis (diet, energy)

Etc. Restrictive life Long waiting list

Indication

• DM• Malignant HTN• Glomerulonephritis• Hereditary (polycystic kidney) -AD-• Lupus• Tumour(??)

75%

NAWAR NADHRAH BINTI ABDUL WAHID

10-5-241Contraindications for Kidney

Transplantation

Absolute Contraindication

Life threatening condition:-untreated cancer

-infection that cannot be treated

-uncorrectable heart disease

History of chronic non-compliance to treatment:

-affect ability to fully care for themselves

History of chronic and ongoing drug/ alcohol abuse

that cannot be treated :Risk to continue abusing

after transplantation

History of serious psychiatric disease that cannot

successfully treated :Risk for ongoing increased

severity

Relative Contraindication Treated malignancy.

-The cancer-free interval required will vary depending on the stage and type of cancer.

-Consultation with a board-certified oncologist is required in most cases.

-Most centers need 2-5 years of cancer free diagnosis before he could be enlisted in the

candidate to receive living donor organ.

Substance abuse history.

-Patients must present evidence of involvement in at least 12 months of drug-free

rehabilitation.

-This includes written documentation of participation in rehabilitation including negative random

toxicologic screens.

Chronic liver disease.

-Candidates with chronic hepatitis B or C or persistently abnormal liver function testing must have

hepatology consultation prior to transplantation.

Cardiac disease. -All patients over the age of 55 or those with a history of diabetes, hypertension, or tobacco abuse must have dobutamine stress echocardiography, or exercise or pharmacologic stress cardiac scintigraphy. -Any patient with a history of a positive stress test or history of congestive heart failure must have cardiology evaluation prior to transplantation.Structural genitourinary abnormality or recurrent

urinary tract infection.-Urologic consultation is required prior to transplantation.

Past psychosocial abnormality. -Master of Social Work (MSW) or psychiatry evaluation, as appropriate.Aortoiliac disease.-Patients with abnormal femoral pulses or disabling claudication, rest pain or gangrene will require evaluation by a board certified vascular surgeon prior to consideration.-Patients with significant aortoiliac occlusive disease may require angioplasty or aortoiliac grafting prior to transplantation.

NUR AFIQAH AUNI ZAWAWI 10-5-242

Prognosis and Outcomes of Renal Transplantation

Overall, average kidney survival times are:• 1 year – 85-95%• 5 years – 70-80%

• 15 years – 50-60%

• Kidney transplantation is a life-extending procedure. • People generally have better quality of life, and fewer

complications with a kidney transplant than if they stay on conventional dialysis.

• The typical patient will live 10 to 15 years longer with a kidney transplant than if kept on dialysis.

Factors that may affect prognosis

1. Deceased and living donors2. Age of donor and recipient3. HLA-matching4. Cold ischaemia time5. Time on dialysis6. Overall health of the person

receiving the donation

NUR AFIQA BINTI ROSLAN 10-5-243

Preprocedural Care

Basic Pretransplant Studies

Pysical examination

Chest x-rayElectrocardiogram

EchocardiogramUltrasound with doppler

examinationPulmonary function

Upper GI seriesLower GI series

Viral testingMammogram

Pap smearDental evaluations

Blood testsBlood typingTissue typing

Panel reactive antibody (PRA)

Renal function studies

Donor GFR at least 80 ml/minCT – Renal

vasculature and parenchymal abnormalities

Steps will precede the transplant

Explain the procedure

Receive dialysis (on

routine)

Living transplant ( fast 8 hours)

Cadaver organ transplant (fast when

notified kidney available)

Receive sedative

sign a consent

Other specific preparation

(based on medical condition)

NUR AKMA ZAINAL SHAHROM10-5-244

Matching of Donors and Recipients

Histocompatibility (HLA) matching

• transplant outcome correlates with number of HLA mismatches.

• HLA incompatibility proliferation & activation of recipient’s

CD4+ & CD8+ T-cells activation of B-cell allo-antibody

production cellular and humoral graft rejection

• HLA-A, HLA-B, and HLA-DR phenotypes should be determined in all

potential recipients and donors.

Cross-matching• detects preformed allo-antibodies in recipient’s serum

directed against lymphocytes of the potential donor.

• carried out using unseparated lymphocytes or T-

enriched lymphocytes of the potential donor

• complement-dependent lymphocytotoxicity (CDC)

assay.

• positive T-cell cross-match is a contraindication to

transplantation.

Panel Reactive Antibodies (PRA)• results of HLA-antibody testing in a recipient’s serum expressed

as the percentage of panel reactive antibodies (%PRA) and as

the HLA specificity against which these antibodies react

• Sera from potential organ recipients screened for HLA-specific

antibodies every 3 months or 2 and 4 weeks after every

immunising event.

• flow cytometry & ELISA (use solubilised/recombinant HLA

molecules instead of lymphocytes more specific &

sensitive

ABO compatibility

• blood group antigens can behave as

strong transplant antigens.

• incompatibility in the ABO antigen system between donor and

recipient can cause early HAR (hyper-acute rejection).

• introduction of antibody elimination methods and anti-B cell

agents increased numbers successful ABO-incompatible

transplantations (even without splenectomy).

NURUL IMAN BINTI ZULKEFLI10-5-245

Postoperative Care

POSTOPERATIVE MANAGEMENTPostoperative management involves 2 key tasks :

1) Maintain the normal fluid balance.With improving renal function:

• fluid balance must be maintained• hypertension management may need modification, and• electrolyte abnormalities may require correction.

2) Administration of immunosuppression.Current immunosuppressive therapy can be divided into 2 phases : induction and maintenance

IMMUNOSUPPRESSIVE DRUGSCalcineurin inhibitors

•Cyclosporin•Tacrolimus•Sirolimus

Antiproliferative agent

•Mycophenolate

Steroid

•Prednisone

IMMUNO SUPPRESSIVE

DRUGS

EXAMPLE OF DRUGS NAME

MECHANISM OF ACTION SIDE EFFECTS ADVANTAGES

Calcineurin inhibitors

CyclosporineTacrolimus

Target proliferating T cells by blocking the elaboration of cytokines

•Dose-related nephrotoxicity•Hypertension

Antiproliferative agent

Mycophenolate Inhibits de novo synthesis of purines during the S phase

•Nausea•Diarrhea

reduces interstitial fibrosis associated with chronic rejection in animal models

Steroid Prednisone •bone disease•hypertension•peptic ulcer disease•glucose intolerance•growth retardation•infection•obesity•lipid abnormalities

A key role in induction and maintenance of immunosuppression and in treatment of rejection

NURUL AQMAR MOHD SUHAIMI10-5-246

Technique Of Living Donor Renal Transplantation

LAPAROSCOPIC DONOR NEPHRECTOMY

• Tiny incisions and a scope or camera• Shorter recovery period • Complication rate : very low• Quality and function of the transplanted kidneys are excellent.• significantly better long-term survival than kidneys from a

deceased donor• New technique - Embryonic natural orifice transumbilical surgery (e-NOTES) - Laparoendoscopic single site (LESS) surgery

• Blood Type Incompatible• Paired Exchange• Plamapheresis• Positive Crossmatch• Waiting List Exchange• Blood Type Incompatible

Kidney Transplant

Potential Barriers to Living Donation• Age < 18 years• Uncontrollable hypertension• History of pulmonary embolism or

recurrent thrombosis• Bleeding disorders• Uncontrollable psychiatric illness• Morbid obesity• Uncontrollable cardiovascular disease• Conronic lung disease• History of melanoma• History of metastatic cancer• Bilateral or recurrent nephrolithiasis

(kidney stones)• Chronic Kidney Disease (CKD) stage 3 or

less• Proteinuria > 300 mg/d excluding

postural proteinuria• HIV infection

Special programs for living donor transplants

NURULZIANI IZZATI BINTI MOKHTAR10 – 5 – 248

Renal Transplantation from

Deceased Donor

• Deceased donor can be divided into two groups:

Brain-dead (BD) donors

Cardiac Death (DCD) donors

• their heart and body is maintained alive but their brain has died.

• Their bodies are maintained on a breathing machine

• their families are asked to give consent for their organs to be used for transplantation

• patients who do not meet the brain-dead criteria

• They have unlikely chance of recovery,

• elected via a living will or through family to have support withdrawn

special priorities for transplantation:

•HLA zero-mismatch pairings (because of their documented improved graft survival rate)•Pediatric recipients (to minimize the impact of chronic renal failure on growth)•Patients with a high panel-reactive antibody titer (to increase their probability of transplantation)

CONTRAINDICATIONS:• active infections• HIV infection• extracranial malignancy• poor renal function in the donor • advanced donor age

ADVANTAGES

50/50 chance of maintaining their function for 10-20 years post-

transplant

50-60% are fully functional immediately upon transplantation

living donor does not need to undergo a kidney donor operation

which has associated discomforts and risks

a kidney can last up to 72 hours before being transplanted due to: advances in preservation techniques

• Intravascular perfusion of the involved organs with cold (ie, 4°C) preservation solution (UW solution) which contain:

high levels of potassium impermeant sugars albumin or dextrans free radical scavengers and other

agents (eg, allopurinol)

kidneys are removed with care

packed sterilely in UW solution and kept at 4° C during transport to the appropriate transplant centers

NURUL ATIQAH BINTI ABU SAHMAH10-5-250

Ureteroneocystostomy & Ureteroureterostomy in Renal

Transplant

URETERONEOCYSTOSTOMYUretero-neo-cysto-stomy (UNC):• Means reimplantation of the ureter into the bladder.• UNC is performed by bringing the ureter through a

tunnel in the bladder submucosa (Leadbetter-Politano approach).

URETEROURETEROSTOMYUretero-uretero-stomy (UU):• Means anastomosis of the segments of ureter, with

excision of the intervening injured or scarred ureter

Maybe a direct uretero-ureterostomy (end-to-end) or transuretero-ureterostomy (end-to-side)

• Only done if anastomosis of the ureter to the bladder ureteroneocystostomy (UNC) is not possible. – Defunctionalized native’s (recipient) bladder– Devascularized donor’s ureter

End-to end End-to-side

NURUL AWATIF BINTI ABD RAHMAN 10-5-251

Complications of Renal Transplantation

Anatomic complications of surgery• Renal artery thrombosis is a complication most commonly seen in the

hospitalization period immediately after transplantation. It is caused by a low-flow state from hypotension or vascular kinking due to surgical error.

• Renal artery stenosis is typically a later complication. It presents as uncontrolled hypertension, allograft dysfunction, and peripheral edema.

• Urine leaks occur at the ureterovesical junction .They result from disruption of the anastomotic connection of the ureter to the graft, generally within the first 2 months after transplantation.

• Ureteral stenosis and obstruction are relatively late complications, occurring months or years after.Ultrasonography reveals hydronephrosis.

• Lymphocele, a circumscribed collection of retroperitoneal lmph as a result of operative trauma to lymphatics. It presents as a mass at the graft site that can impinge on and obstruct the ureter.Occuring 1-2 months after transplantation.

Computed tomographic- angiography demonstrates (arrow) a proximal stenosis of the transplant kidney artery.

Allograft dysfunction and rejectionHyperacute rejection -happens in the operating room within hours of the

transplant.- due to unrecognized compatibility of blood groups A, AB, B, and O (ABO) or to a positive T-cell crossmatch (class I human leukocyte antigen [HLA] incompatibility)

Acute rejection -appears within the first 6 months after transplantation- Rejection is secondary to prior sensitization to donor alloantigens (occult T-cell crossmatch) or a positive B-cell crossmatch.

Chronic rejection -rejection occurs more than 1 year after transplantation and is a major cause of allograft loss.-Requires clear strong evidence for a solely chronic immunological process.- Certain non-specific histological features and/or anti-HLA antibodies.

Infections

• Infection due to the immunosuppressant drugs that are required to decrease risk of rejection.

• Infection most commonly occurs in mucocutaneous areas , the urinary tract , and the respiratory tract .

• Cytomegalovirus , herpes simplex virus , and varicella-zoster virus are the most frequent viral pathogens. Infection is the most common cause of death, such as pneumonia.

Malignancy -Transplant recipients higher risk for many cancers than

members of the general population as a result of the following factors:

• Chronic immunosuppression• Chronic antigenic stimulation• Direct neoplastic action of immunosuppressants

-Transplant recipients are at particularly high risk for infection-related malignancies, such as non-Hodgkin lymphoma, Hodgkin lymphoma, and Kaposi sarcoma,.

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