1. Renal transplantation

2. is the procedure of choice & the most cost effective strategy for the management of pt with end stage renal disease.
Successful renal transplant is associated with
substantial improvement in quality of life
significant reduction in morbidity & mortality from end stage renal disease.

3. Patient Survival After Kidney Transplantation VS haemodialysis
Annual mortality rates for patients under dialysis range from 21%-25%, but <8% with cadaveric and <4% with living-related transplant recipients.
Healthier patients generally are selected for transplantation.
The benefit of transplantation is most notable in young people and in those with diabetes mellitus.

4. Previously the outcome of pt with chronic renal failure is dialysis to get rid of waste product of metabolism (nitrogenous & non nitrogenous substance) either by peritoneal or hemodialysis.
Indications for dialysis in the patient with acute kidney injury are summarized with the vowel acronym of "AEIOU“
1- Acidemia from metabolic acidosis in situations in which correction with sodium bicarbonate is impractical or may
result in fluid overload.
2- Electrolyte abnormality, such as severe hyperkalemia, especially when combined with acute kidney injury.

5. 3- Intoxication, that is, acute poisoning with a dialyzable substance
3- Intoxication, that is, acute poisoning with a dialyzable substance. These substances can be represented by the mnemonic SLIME: salicylic acid, lithium, isopropanol,
magnesium-containing laxatives, and ethylene glycol.
4- Overload of fluid not expected to respond to treatment with diuretics.
5- Uremia complications, such as pericarditis, encephalopathy, or gastrointestinal bleeding.

6. *kidney normally responsible for
1- water & electrolyte balance.
2- maintenance of acid base balance of the body.
3- excretion of waste products
(urea, uric acid, & creatinine ).
4- production of erythropoietin necessary for erythropoiesis.
5- renin secretion & hydroxylation of V.D3 to 1, 25
dihydroxycholecalceferol which essential for
bone.

7. Selection & preparation of recipient
The causes of renal failure include
diabetes 36%,
hypertension nephrosclerosis 30%,
chronic glomerulonephritis 24%,
autosomal dominant polycystic kidney disease 12%,
Renal failure in children <18 yr old
congenital urologic condition
(hydronephrosis with obstruction or congenital atrophy) as major cause 45% of renal failure.

8. Contraindications of renal transplantation
Today there are few absolute contraindications to renal transplantation other than
-active infection
-active malignant disease
Usually upper age limit is 70 yr, however
pt with life expectancy < 5yr should be maintained on dialysis.

9. CONTRAINDICATIONS TO RENAL TRANSPLANTATION
ABO incompatibility.
Cytotoxic antibodies against HLA antigens of donor.
Recent or metastatic malignancy.
Active infection.
AIDS.
Severe extrarenal disease (cardiac, pulmonary, hepatic).
Active vasculitis or glomeulonephritis.
Uncorrectable lower urinary tract disease.
Noncompliance.
Psychiatric illness including alcoholism and drug addiction.
Morbid obesity.
Age > 70 years.
Primary oxalosis.
Persistent coagulation disorder.

10. Access to circulation by doing external fistula connecting artery to vein like posterior tibial artery with short saphenous vein done to ensure preoperative hemodialysis.
Preoperative blood transfusion of at least 5 unit of blood during the period of hemodialysis appear to produce better result by diminishing the result of certain tissue type mismatch
(the best is donor specific blood transfusion).

11. Nowadays with the era of
-cyclosporine &
-synthetic erythropoietin
blood transfusion no more indicated.

12. Pretransplant bilateral native kidney nephrectomy
Seldom required , common indication include:
1- Infection
(pyelonephritis, huge kidney filled with pus).
2- Malignant disease.
3- Medically uncontrolled renin mediated hypertension
4- Nephrotic syndrome.
5- Other less common like polycystic disease.
Bilateral laparoscopic nephrectomy has obvious advantages over the open approach.

13. Selection of donors
1-Living related donors (LRDs)
The potential donor must be free of any condition that increase risk of any complication from the operation, diminish the function of remaining kidney, or change their baseline quality of life.
First-order LRDs continue to provide significantly higher success rates in renal transplantation than cadaveric donors.

14. CRITERIA FOR LIVING DONOR SELECTION
Blood relative.
Highly motivated.
ABO blood group-compatible.
HLA-identical or haploidentical with negative cross-match.
Excellent medical condition with normal renal function.

15. 2-Living unrelated donors (LURDs)
LURDs should be considered only when medically & ethically appropriate to circumvent the worldwide shortage of organs from cadaveric donors.
It is medically acceptable if better result can be expected compared with cadaveric renal transplantation
Its ethically appropriate if enduring relationship between the donor & recipient exists, such as spousal donation.

16. Principles Involved In evaluating A Prospective Living Kidney Donor
Whether there is a medical condition that will put donor at increased risk for complications for general anaesthesia or surgery.
Wether the removal of one kidney will increase the donor’s risk for developing renal insufficiency.

17. Evaluation Of Kidney Function In Potential Kidney Donor
Serum creatinine.
Creatinine clearance.
Radionuclide glomerular filtration rate.
Urine analysis.
Urine Culture.
GFR > 70 ml/min.

18. Medical Conditions That Exclude Living Kidney Donation
Renal parenchymal disease.
Conditions that may predispose to renal disease
History of stone disease
History of frequent UTI
Hypertension
D.M.
Conditions that increase the risks of anaesthesia and surgery.
Recent malignancy.

19. when these criteria are used, the result of LURDs superior to cadaveric because of excellent physiologic quality (no preservation or ischemic injury)

20. Does Donation Of A kidney Pose A long-term Risk For The Donor?
Following nephrectomy, compensatory hypertrophy and increase in GFR occur in the remaining kidney.
Slight risk of poteinuria and hypertension.
Meta-analysis of data from donors followed for >20y confirmed safety of kidney donation.

21. 3-Cadaveric donors
Should not have any generalized disease that could adversely affect renal vascular integrity or perfusion, such as
chronic hypertension,
diabetes,
malignant disease
(with significant metastatic potential)
infection.

22. CRITERIA FOR CADAVER DONOR SELECTION
Irreversible brain damage.
Normal renal function appropriate for age.
No evidence of preexisting renal disease.
No evidence of transmissible diseases.
ABO blood group-compatible.
Negative cross-match.
Best HLA match possible, particularly at the DR and B loci.

23. In older donors or those with questionable systemic disease such as hypertension renal biopsy should be considered.
A biopsy finding of
significant glomerulosclerosis (>10-20%),
intimal hyperplasia,
interstitial fibrosis,
tubular atrophy, or
evidence of disseminated intravascular coagulopathy
renders the donors unacceptable.
High risk for HIV pts are unacceptable donors.

24. Compatibility
The principle histocompatability antigens are
major histocompatability complex (MHC) &
blood group.
The human MHC isolated on the short arm of chromosome 6 and include the genetic loci A, B, C, & D (DR, DQ, DP).
these genetic loci code antigen specialties which are detected on peripheral blood lymphocyte & known as human leukocyte antigen (HLA).

25. The antigens of genetic loci A, B, C can detected by tissue typing serology,
while antigen of D locus is detected only by mixed leukocyte culture (MLC). Which is done by mixing lymphocyte of donor & recipient in a tissue culture & it take about 5 days until we take the result,
it measure cell to cell reaction of lymphocyte.

26. This culture is not practical for cadaveric kidney because it take long time & in best way to preserve the kidney usually no more than 2 days.
HLA locus is the most important one in these reaction so
if the result is +ve indicate incompatibility
if –ve compatibility & transplant is possible.

27. Operative procedure
1-Donor operation
Routine nephrectomy,
give dopamine & chlorpromazine for donor developing hypotension & impaired renal function.
Preservation of kidney rarely necessary.
2-Recipient operation
Clear the external & internal iliac vessels from LN & adipose tissue.

28. Transplanted kidney best position is in iliac fossa.
The renal artery is anastomosed to external or internal iliac artery
the vein to external iliac vein & finally
the ureter is implanted to the urinary bladder.

29. An adult donor kidney transplanted to the left iliac fossa of an adult recipient.

30. Post operative management.
The pt receive immunosuppressive therapy 24hr before operation & after transplantation for rest of his life except in case of transplant from identical twin.

31. Drugs.
1- Azathioprine. 3mg/kg cause bone marrow depression.
2- Cyclosporine. above 10yrs.
3- Steroid. Prednisolone.
4- Antilymphocyte globulins which is polyclonal nonspecific drugs.
5- Antibodies purified to IgG.
6- OKT3 which is monoclonal antibody against specific T-cell Ag.
7- Generally fluid balance, urinary out put is measured hourly & replaced with dextrose saline.

32. Complications
1-technical. Including vascular, urinary extravasations or obstruction to the outflow of urine or lymphatic obstruction.
Lymphocele may occur which is a big mass can be palpated on abdominal examination due to collection of lymph occur as a result of dissection of lymphatic vessel during surgery.
-It doesn’t affect the function of kidney but require treatment which is done surgically by draining the lymphocele to peritoneal cavity

33. 2-infection
The most common cause of death after transplantation occur due to
the use of immunosuppressive drugs so the body infected easily with impaired defense mechanism
steroid in high doses delay healing & mask classical physical sign of disease such as pneumonia or acute abdomen.

34. Example of these opportunistic infections are
pneumocystic carini,
pneumonia,
monilia,
CMV, &
staphalbus infection.
*also high doses of steroid may cause osteonecrosis
(a vascular necrosis) of the neck of femur.
Development of malignancy may occur such as caposi sarcoma.

35. 3-Acute tubular necrosis (ATN)
is the commonest cause of post operative anuria, tubular cast may be seen in urine. Hemodialysis may be necessary (will recover spontaneously) .
4-Rejection
All transplants have some degree of rejection the sever form is

36. Hyperacute rejection
may occur within minutes of completion of operation this is seen in ABO incompatibility or in recipient sensitized by multiple blood transfusion when occur it is associated with intrarenal coagulopathy & gross platelets aggregation
Acute rejection
which may occur even with HLA compatibility & may be seen 3 months after transplant.
Chronic rejection: occur many months after transplant associated with arterial damage in the kidney

37. Features of rejection in general
decrease urinary flow,
increase blood urea & creatinin, with
tenderness on examination over grafted kidney &
sometime fever & hypertension
*Diagnosed by radioisotope scanning & renal biopsy done to differentiate rejection from ATN

38. Rejection treated by
extensive immunosuppressive therapy for 3 successive days with monitoring blood urea & creatinin & urine out put.
Some time external irradiation restricted to the transplant margin or even
splenectomy in cases of leucopenia.

39. D.Dx of post transplant oliguria
1-Acute tubular necrosis.
2-Rejection.
3-Obstruction of collecting system.
4-Infarction due to false operative technique.

40. A healthy child born to a female transplant recipient, 3 years after a successful engraftment.