Renal transplantation

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. 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.

4. *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.

5. 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.

6. 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.

7. 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).

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

9. 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.

10. 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.

11. 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.

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

13. 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.

14. 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.

15. 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).

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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

23. 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.

24. 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.

25. 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

26. 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

27. 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

28. 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.

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