Urology Journal UNRC/IUA Vol. 2, 8-13 Spring 2004 Printed in IRAN 8 Review Article Preparing Live Donor for Kidney Donation MAHDAVI R Department of kidney transplantation, Imam Reza Hospital, Mashhad University of Medical Science, Mashhad, Iran ABSTRACT Purpose: In order to select the most appropriate donor and minimize psychological and physical complications in the kidney donors, it is of high importance to prepare the donor meticulously. The essential respective items are reviewed in this study. Materials and Methods: The available published literature and papers presented in Medline from 1983 to 2003 were reviewed. Results: One the sources of sources of kidney donation is the live donor which is mostly used in Iran. Similarly, due to long waiting lists of kidney recipients, live donor kidney transplantation have been increasingly used in developed countries. Consequently, several aspects of this issue have been considered and specific recom- mendations have been discussed; anatomy of the donor's kidney, age, ABO blood group, viral infections, weight, HLA type compatibility, psychological status, and dis- eases such as diabetes, ADPKD, and Alport syndrome should be evaluated in donation candidates. Conclusion: Live donor kidney donation has the advantage of elective and pro- grammed transplantation over cadaveric transplantation. However, removal of an intact organ from the body of a normal individual may lead to complications, as it may so in any other major surgical operation. Thus, it is strongly recommended to select the most appropriate donor patiently by a series of accurate evaluations. KEY WORDS: kidney, transplantation, donation, alive Introduction In 1954, the first successful kidney transplanta- tion was performed in a 23-year-old male receiving kidney from his twin brother by Dr. J.E. Murray in Boston. This procedure, without any use of immunosuppressive medication, provided a nor- mal life until the recipient died of a non-renal cause.(1) Between 1954 and 1980, desirable out- comes were achieved by using related donor, due to the tissue compatibility between the recipient and the donor, but transplantation from cadaver which was accompanied with serious complica- tions was not popular; Freeman reported that patients would still have preferred hemodialysis to transplantation in 1985s.(2) Better understanding immunological aspects, particularly introducing Cyclosporine and mono- clonal and polyclonal antibodies, yielded an improvement of short-term graft survival, but it was not significant yet. Even live related donor transplantation was disputed by Starlz in 1987.(3) However, Terrasaki and Cecka demonstrated the advantage of related or unrelated live donor trans- plantation over cadaveric transplantation, despite of new medications usage. In 1998, they observed that transplantation from related or unrelated donor results in a 10-15% and 10-12% higher 1- and 5-year graft survivals than from cadaver.(4,5,6,7) Nowadays, kidney transplantation is more requested due to better hemodialysis status and higher ESRD patients' survival. While cadaveric donation for transplantation is increasingly used PREPARING LIVE DONOR FOR KIDNEY DONATION in developed countries, the number of patients waiting for transplantation has risen in parallel. For instance, annual report of Eurotransplant in 2000 revealed that only 3145 patients out of 12524 (25%) in the waiting list has received transplanted kidney of which 569 (18%) received from living donors.(8,9) Also in the United States where they have a long-term established programme for cadaver transplantation, because of the increase in ESRD patients waiting list, living donor transplan- tation has been increased and unrelated donors (spouse, friend, etc.), previously comprised 4.1% of the total living donors in 1988, have reached 14.2% in 1996.(5,8) At the moment, they serve as 20 to 27% of living donors for kidney transplantation in the United States.(9) Moreover, since laparoscopic nephrectomy tech- nique has been introduced with low postoperative complication rate, more people are encouraged to donate kidney.(4,10) Discussion One of the most pivotal advantages of living donor transplantation, as well as providing pro- grammed procedure in a desirable condition and at a proper time, is that long-term hemodialysis which is associated with the risk of rejection, par- ticularly if frequent transfusion had been required, could be prevented.(11) Consequently, some author- ities prefer pre-emptive transplantation, specially in children and diabetic patients in whom dialysis leads to various medical problems.(5) Does donation impact the donor's phys- ical health condition? This is a frequently asked question by donation candidates. The answer is that short-term non-spe- cific complications such as hemorrhage, infection, wound problems, and even death are inevitable as they are in any major surgical operation, but stud- ies with long-term follow-ups have shown that 5- year life expectancy of 35 year old donors is 99.1% which is not significantly different from that in general population (99.3%). Also an eligible life quality has been reported in kidney donors.(12,13) Does the removal of one kidney have unfavourable effects on the other kidney? Studies on rats have revealed that eliminating one kidney causes hyperfilteration in the form of sclerosis progression and reduction of the spared kidney function.(14,15) Whereas, 20-year follow-up of hundreds of donors and those who have lost one kidney due to urological problems, have shown that the solitary kidney has appropriate function till the end of life, besides a preliminary compen- sating hypertrophy,(12,13,16,17) so that the insurance companies consider kidney donors as normal indi- viduals.(18) Few studies have reported that in long- term after donation microalbuminuria and pro- teinuria increases the risk of hypertension to a lit- tle extent.(19) Although living donation has a great advantage over cadaver donation, we should consider that the removal of a normal organ from a normal individ- ual has its own risk of complications like any other major operation. Hence, in order to reduce psycho- logical and physical complications as far as possi- ble, it is necessary to select and prepare the donors meticulously. Here is a review of the stages of this process: Psychological Evaluation Psychological assessments are necessary to con- firm psychological stability of the donor, as the rate of depression, anxiety, and even suicide fol- lowing the kidney donation is 1.5% or more.(20,21) These problems are often seen in the donors who were not completely contented with donation for any reason or in the cases of graft failure. Consequently, it is recommended to continue psychological follow-up after the procedure. When the donor is a relative of the recipient, his/her consent should be confirmed to avoid obligatory donation. It is suggested that the donor's most intimate relatives such as parents and spouse be aware of the donation procedure. This is of utmost importance in countries such as Iran in which most donors are not related to the recipient. Donor's Age A proper age is within the range of 18 to 60 years, but recent reports have shown that an exact age limit can't be defined, because biologic age plays a more decisive part than true age does. Kanesmasu and coworkers presented the out- comes of transplantation from 518 over-60-year-old donors and they found that although graft survival in the first years was not meaningfully different from the control group (89% vs. 91%), serum crea- tinine level was higher even in the fist years and 4-year graft survival difference was more pro- 9 PREPARING LIVE DONOR FOR KIDNEY DONATION nounced (76% vs. 81%). They concluded that kid- ney donors older than 60 should be selected for older recipients.(22,23,24) Abo Blood Group The Donor's ABO blood group should be matched with the recipient's. Otherwise, irre- versible graft rejection will occur in the presence of blood group incompatibility. Rh factor does not impact the outcomes, so donor can be either Rh positive or Rh negative. In the countries in which they don't use unrelat- ed donors, due to the limited number of donors, transplantation from the donors with A2 blood group (20% of people with A blood group) or B subgroups to the recipients with O blood group have been performed successfully. In such cases plasmapheresis precedes the pro- cedure in order to eliminate anti-A and anti-B anti- bodies and to prevent acute rejection. In addition, by Donor-Specific Skin Grafting test they evaluate the preparation for transplant; any inflammatory reaction in the skin graft region predicts a poor prognosis for the kidney graft.(25,26) Immunologic Tests T-Lymphocyte test is the first donor-recipient immunologic test to be done. In this test the reac- tion between the donor's lymphocytes and the recipient's serum is studied. When more than one properly matched donor is available, the one with completely negative T-lymphocyte test will be selected.(27) Some centers consider Mixed Lymphocyte Reaction test (MLR), but new immunosuppressive medications have disputed the value of this test and currently it is just useful to select the best donor from among the family members who all have HLA compatibility with the recipient.(27) When there are a few serologic compatible donors in a family, HLA Tissue Typing should be done to select the one who is HLA identical. History Taking and Physical Examination In the cases of chronic renal failure, due to Autosomal Polycystic Kidney Disease (ADPKD), Alport syndrome, hypertension, and diabetes, meticulous evaluation of the related donor is war- ranted. Diagnostic criteria for ADPKD have been identified; Ravine (1994) suggested the number of cysts in each kidney of the patients with positive family history detected by ultrasonographic stud- ies be used to classify the criteria: Two cysts in one of the kidneys or both in patients under 30 years old, two cysts in each kid- ney of patients between 31 and 59, and four cysts in both kidneys of over-60s must be considered as ADPDK.(27) It is also recommended to select relat- ed donors of over 30 to be able to identify the cysts by CT scan using rapid injection of contrast media and prevent transplantation of polycystic kidneys.(28,29) Alport syndrome may present with microscopic hematuria and proteinuria in the family members and renal biopsy can provide the definite diagno- sis if needed.(30) These patients should be exclud- ed from the donors list. Hypertension is often a hereditary transmitted disease and also, it is seen in 15 to 25% of the patients over 50 years old.(31) Consequently, candi- dates for kidney donation should undergo blood pressure evaluation in three separate times and sometimes even 10 times.(17) A series of examina- tions have been recently recommended to be done in donors with borderline blood pressure including echocardiography, intima and media thickness measurement of carotid vessels, examination of retina, and urinary albumin concentration, all demonstrating the subsequent damage to the eye and kidneys.(17) Furthermore, it has been proved that hypertension can be transmitted to the recip- ient by the transplanted kidney.(32) Generally, patients with a blood pressure of 140/80 or more, with persistent diastolic pressure of over 90 mmHg, or who need medication to con- trol the blood pressure are not appropriate candi- dates for donation and should be excluded.(32,33) Diabetes Mellitus Type II diabetes mellitus incidence is increasing nowadays; reports have shown that 6% of the peo- ple will have diabetes by the age of 50 and 20% by 70.(9,27) Thus, evaluation of latent diabetes is very crucial. In addition, there are a few reports repre- senting the development of latent diabetes to an apparent diabetes following nephrectomy that leads to diabetic nephropathy in the donor.(34) Consequently, in some centers they evaluate relat- ed donors of a diabetic recipient by the measure- ment of Hb A1c2 and Anti-Islet Antibody as well as a 5-hour glucose tolerance test.(9) In some cases proteinuria should not be present in a 24-hour urine collection specimen and it is recommended the age of the donor to be at least 10 PREPARING LIVE DONOR FOR KIDNEY DONATION 10 years more than the age of the recipient at the time of diabetes onset. Eventually, kidney dona- tion must not be done in case of a positive Glucose Tolerance Test.(9,34) Obesity Overweight more than 30% of the ideal body weight is a relative contraindication for donation and patients are recommended to lose weight before kidney transplantation science obesity may cause pulmonary emboli or cardiovascular compli- cations as well as problematic nephrectomy.(8,27) A history of thromboembolism or thrombophlebitis increases the risk of pulmonary emboli in the donor, so that they had better be excluded.(15,27,33) Paraclinical Evaluations Biochemical and serologic tests: Complete blood count, coagulation tests, renal function tests (BUN, creatinine, and creatinine clearance), liver function tests, serum cholesterol, calcium, and phosphorous, urine analysis and culture, 24-hour urine collection test, and serologic tests for viral infections should be requested for donors. The most common serologic tests are the ones for antiviral antibodies of CMV, HIV, Hepatitis B, Hepatitis C, HTLV I, and HTLV II. HIV Antibody: A positive HIV Antibody is the absolute contraindication of transplantation. CMV Antibody: CMV is one of the most preva- lent post-transplant infections that can influence mortality, morbidity, and graft survival. It is also responsible for acute graft rejection. Detecting IgG antibody, using ELISA, is necessary to indicate CMV infection. The risk of CMV disease must be assessed if CMV antibody is positive.(35) Transplantation of a recipient with negative CMV IgG from a CMV positive donor has a great risk of CMV disease in the recipient and may develop 4 to 5 weeks after the procedure. As a result, prophylactic Ganciclovir is highly recom- mended.(9) Hepatitis B and C: Hepatitis is a frequent lead- ing cause of chronic liver failure that may present with cirrhosis, liver failure, and liver cancer.(36,37) Consequently, HBs-Ag positive donors must be excluded from the transplant program, but dona- tion from a HBs-Ag negative but HBc-Ab positive is possible since it has proved not to have any effect on the graft or morbidity and mortality at least in short-term, despite of its relative risk of HBV infection.(37) Being Anti-HCV positive is not an absolute con- traindication for kidney donation, but interferon therapy is necessary before donation, because Hepatitis B or C virus transmission is accompa- nied with difficulty to treatment as interferon rap- idly increases rejection risk.(36) Totally, kidney donation from a hepatitis C disease positive patient is not recommended if we presume a long- term survival.(36,37,38) HTLV I: Human Lymphotrophic Virus type I is the first known retrovirus in the human, spread worldwide. The most considerable epidemiologic characteristic of the infection is the existence of highly endemic areas such as Iran, specially Khorasan.(39) Ten to 20% of individuals with HTLV I infection will have HTLV I associated diseases such as T cell leukemia of adults, myelopathy, uveitis, etc.(39,40) Accordingly, Anti HTLV I test is a routine exam- ination in kidney donors and in case of a positive result transplantation should be canceled if the recipient is anti-HTLV I negative. Radiological Studies Imaging studies are done when all the previous- ly mentioned steps are passed without any prob- lem. Chest x-ray and renal ultrasonography are first to be performed. If ultrasonography showed no abnormality, a selective arteriography of the kidney with excretory phase could be requested. Pyelocaliceal system is detectable in the excreto- ry phase of the kidney, so that IVP is not neces- sary before angiography.(41) Today, we can benefit from 3-dimensional or spiral CT scan in order to investigate detailed anatomy of the kidney. This method is more helpful in centers in which laparo- scopic nephrectomy is performed.(9,42) Catheter inserting into renal vessels is no more needed when using these new methods. However, it is note worthy that making final diagnosis of vascular lesions, particularly of small renal vessels such as unilateral fibromascular dysplasia is more attainable by angiography.(43) We can use Digital Subtraction Angiography (DSA) rather than con- ventional angiography to avoid catheterization and its complications.(8,43) Angiography can show the existence of one or more arteries for the kidney. It is obvious that a kidney with one artery is preferred. Also, the left kidney is more desirable due to its longer vein. We can eliminate vascular lesion after nephrectomy if anomalies such as aneurism or fibromascular renal artery stricture, limited to the beginning of 11 PREPARING LIVE DONOR FOR KIDNEY DONATION the artery, is present. However, nephrectomy is just permitted only if the spared kidney of the donor is completely normal.(8,15,44) In our center, over a 12 year period, from among 715 donors, there were 26 cases with two renal arteries and 2 cases with 3 arteries. Only 7 of 26 cases with two renal arteries were unrelated donors. In young female donors in whom pregnancy is anticipated in the future, right kidney should be selected for nephrectomy since obstructive uropa- thy due to pregnancy often occurs in the right kid- ney. As a rule in live donor nephrectomy, the more intact kidney is preserved for the donor. This rule must be considered in all cases. Relative and absolute contraindications of kid- ney donation, extracted from European Association of Urologists' (EAU) 2003 guidelines, are shown in tables 1 and 2. As kidney transplantation is a team work and a team consisting of nephrologist, urologist, anes- thesiologist, paraclinics expert, nurses, and opera- tion room group intervene in the procedure, according to our experience, it is suggested that the completed examinations and laboratory results of both donor and recipient may be evaluated in a session by all the team members and controversial items may reassessed to arrive at the operation decision. When all the criteria for donation to a definite recipient are achieved, the donor will be admitted a night before the operation and hydration with a saline or dextrose-saline serum can be initiated in order to preserve ample diuresis during the oper- ation. The anesthesiologist is proposed to visit the donor before the procedure and skilled nurses should educate the patient to prevent post-opera- tive atelectasis and thromboembolic complications. After the anesthesia is brought off and before the skin incision, an intravenous injection of a first or second generation of Cephalosporines (1gr) is suggested. Finally, it is strongly recommended that shaving to be done in the operation room.(27) References 1. Kusse R, Bourget P. An illustrated history of organ trans- plantation: the great adventure of the century. France: Rueil-Malmaison, Sandoz, 1992. 2. Freeman RB. Treatment of chronic renal failure on update. N Eng J Med 1985; 312: 577. 3. Brener BM, Meyer TW, et al. Dietary protein intake and the progressive nature of kidney disease the role of hemo- dynamically mediated glomerular injury in the pathogenesis of glomerular sclerosis in aging renal ablation and intrin- sic renal disease. N Eng J Med 1989; 307: 652. 4. Altani D, Pretagostini R, Rossi M, et al. Living unrelated kidney transplantation. A 12 years single center experience. Transplant Proc 1997; 29(1-2): 191-194. 5. Briggs JD. The recipient of a renal transplant in: kidney transplant principle and practice. 5th ed. W.B. Saunders; 2001. p. 45-58. 6. Cecku JM. The UNOS Scientific Renal Transplantation Registry. Clinic Transplant 1998; 1-16. 7. Terasaki PI, Cecka JM, et al. High survival rates of kid- ney transplant from spousal and living unrelated donors. N Engl J Med 1995; 333: 333. 8. Cosimi AB, Ko SD. The donor and donor nephrectomy. In: Morris PJ, editor. Kidney transplantation. 5th ed. W.B. Saunders; 2001. p. 89-105. 9. Kalbe T, Fulda G, Benort M, et al. Guidelines on renal transplantation. European Urology 2003; 16: 7-9. 10. Ranter LE, Montogery RA, Kavossi LR. Laparoscopic live donor Nephrectomy: A review of the first live years. Urologic clinic of NA; 28 (4): 709-720. 11. Nerurkar VR, Achiron A, Song KJ, et al. 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Contraindications for kidney donation (EAU Guideline, February 2003 Renal Transplantation) Absolute contraindications Age under 18 Hypertension (more than 140/90, requiring medical therapy) Diabetes (impaired GTT or Hb A1c) Proteinuria more than 300 mg/24h Microscopic hematuria History of thrombosis or thromboembolism Significant underlying disease (Chronic pulmonary disease, malignant tumors, cardiovascular disease) History of renal calculus Relative contraindications Donated kidney anomaly (urologic or vascular) Obesity ( 30% more than the ideal body weight) Psychological disorders TABLE 2. 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International prophylaxis trans- plantation study Group. N Eng J Med 1999; 340: 1462- 1470. 36. Otero J, Rodrigues M, Escudero O, et al. Kidney trans- plants with positive antihepatitis C Virus Donors. Transplantation 1990; 50: 1086-1087. 37. Sutterth Waite R, Ozgu I, Shidgan H, et al. Risk of trans- plantation kidneys from hepatitis B surface antibody posi- tive donor transplantation. 1997; 64: 432-435. 38. Karpinski J, Lajoie G, Cattran D, Fenton S, Zatzman J, et al. Outcome of kidney transplantation from high-risk donors is determined by both structure and function. Transplantation 1999; 67: 1162-1167. 39. Faridhosseini R, Pishnamaz M. HTLV1-infection and asso- ciated diseases. MUMS 2002; 45 (76). 40. Safai B, Huang JK, et al. Prevalence of HTLV-I Infection in Iran: Serologic and genetic study. AID Research and HUR; 12: 1185-1190. 41. Spring DB, Salvutierru OJ, Plaubinskas AJ, et al. Results and significance of angiography in potential kidney donors. Radiology 1979; 133: 45-47. 42. Lucan M, Rotariu P, Jacob G, Cohervun L. Technical aspects in retroperitoneoscopic harvesting. The kidney, Abdominal organ transplantation from Living Donors: State of the Art. Hybern 2002; 85 [abstract volume]: 21-23. 43. Davidson RA, Wilcox CS. Newer tests for the diagnosis of renovascular disease. JAMA 1992; 268: 3353-3358. 44. Cragg AH, Smith TP, Thompson BH, et al. Incidental fibromuscular dysplasia in potential renal donors: long-term clinical follow up. Radiology 1989; 172: 145-147. 13