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The Urqlogical Evaluation and Management of Renal Transplant Donors and Recipients
0022-534 7/80/1243-0305$02.00/0
Vol. 124, September
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1980 by The Williams & Wilkins Co.
Review Article THE UROLOGICAL EVALUATION AND MANAGEMENT OF RENAL TRANSPLANT DONORS AND RECIPIENTS DAVID J. CONFER*
LYNN H. BANOWSKY
AND
From the Departments of Urology and Renal Transplantation, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base and University of Texas Health Science Center, San Antonio, Texas
Currently, Medicare is underwriting the expense for approximately 35,000 patients receiving hemodialysis. This figure was 14,000 in 1972 and is projected to reach 60,000 by 1983. Considering the increased willingness to transplant relatively high risk patients, coupled with the ever increasing number of renal failure survivors, we can expect more renal transplants to be done and even more need for urological evaluation of potential renal transplant donors and recipients. TRANSPLANT RECIPIENT EVALUATION
The evaluation of potential transplant recipients is an extensive investigation to uncover any physical or emotional defect that might preclude successful transplantation. A complete history is obtained and physical examination is accomplished. Potential sources of infection and possible malignancies must be discovered, since these may be of devastating consequences to the immunosuppressed, post-transplant patient. Peptic ulcer disease and diverticulitis are relative contraindications to transplantation, unless surgically manageable before transplantation. Consultations for ears, nose, throat and oral surgery are necessary to exclude potential upper respiratory and oropharyngeal sources of infection. A Papanicolaou smear is obtained routinely on all women. Extensive screening laboratory studies are obtained. Proteinuria is quantitated. Lower gastrointestinal studies are obtained on patients >40 years old. Most chronic renal failure patients are hypertensive and the ease of control of this hypertension with adequate dialysis and small amounts of medication is assessed. The patient is scrutinized carefully for a history of urinary tract infection. Neurological and psychological studies are included. Urological evaluation is individualized, often depending on historical factors. If the patient has no history of infections or calculi, or symptoms of voiding dysfunction a voiding cystourethrogram often will be the only diagnostic study needed. Urine for culture is obtained at the time of this catheterization. A history of infection or calculi obligates one to visualize the upper collecting systems, usually by retrograde pyelography. If a possible anatomical source of infection is found pre-transplant nephrectomy will be necessary. Patients with cutaneous diversion, diabetes, pathological voiding symptoms, history of urinary tract infections or calculi, or other evidence of voiding dysfunction receive a thorough lower urinary tract evaluation. These studies include 1) voiding cystourethrogram, 2) cystoscopy and 3) cystometric evaluation with urethral pressure profile and anal or perinea! electromyogram as indicated. Uroflowmetric studies are useful. Peters has reviewed parameters for selecting those patients with satisfactory bladder function in a number of interesting clinical situations. 1 Any urological pro* Requests for reprints: Department of Urology/SGHSU, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas 78236. The views expressed herein are those of the authors and do not necessarily reflect the views of the United States Air Force.
cedure needed to ensure adequate voiding capability, such as a urethroplasty or prostatectomy, is performed well in advance of transplantation. Often defunctionalized bladders are satisfactory, particularly in those patients whose primary disease had been posterior urethral valves. These small bladders may dilate to satisfactory size within a few months. 1• 2 Figure 1, A demonstrates the apparent bladder capacity on cystography of a 17pound, 2-year-old child before transplantation but after valve resection. Figure 1, B shows the extent of bladder enlargement apparent on excretory urography (IVP) 6 weeks after receipt of his mother's kidney. Occasionally, there is uncertainty as to whether the bladder will be adequate for transplantation. This uncertainty is particularly true when the bladder is small and severely trabeculated (fig. 2). Shenasky suggested weekly hydrodilation for a few months in such patients to gain insight as to the distensibility of these bladders. 3 Information regarding continence and the ability to empty also will be useful. 3 Nonetheless, there will be instances in which satisfactory bladder function cannot be assured. In this situation we agree with Peters 1 and others that a satisfactory ileal or colon conduit should be constructed at least 6 weeks before transplantation. A ureterointestinal anastomosis that prevents reflux is desirable. The bilateral nephroureterectomy necessary in those with ureterostomies may be combined with conduit construction. In children with cutaneous diversions these should be studied to eliminate the possibility of stomal stenosis or other obstructive phenomena. Occasionally, dramatic improvement in renal function can be realized with improved drainage. This is particularly beneficial in small children in whom delaying transplantation for 1 or 2 years might allow enough growth for them to receive a related adult allograft rather than requiring a pediatric cadaver kidney. Generally, we do not consider cystectomy for pediatric diversion patients in whom there is a possibility for undiversion in the future, unless persistent lower urinary tract infections are anticipated. This is particularly important with the continual improvement in anti-incontinence procedures. COMPREHENSIVE SURGICAL MANAGEMENT OF RECIPIENT
Vascular access. With the exception of small children most prospective recipients have vascular access for dialysis. These are either external arteriovenous shunts, such as Scribner's shunt, or internal (subcutaneous) arteriovenous fistulas. Shunts have the advantage of immediate use, whereas it is best to wait several weeks to use a fistula. However, fistulas have more likelihood oflong-term patency and less risk of infection. A few centers use peritoneal dialysis routinely, particularly for patients with diabetes mellitus. In our adults satisfactory fistulas are created well ahead of the anticipated dialysis and operation. In children in whom access loss owing to thrombosis is more of a problem this is accomplished in a minimal interval before nephrectomies or transplantation. In general, dialysis on 2 of the 3 days before the operation will minimize the requirement
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FIG. 1. A, apparent small size of bladder after transurethral resection of posterior urethral valves in 2-year-old child before transplantation (maximum filling on high pressure cystogram). B, relative enlargement of defunctionalized bladder noted in part A demonstrated on IVP 6 weeks after transplantation. Fluoroscopy demonstrated complete emptying of ureter without obstruction.
FIG. 2. Small, thickened, trabeculated bladder with capacity of 15 cc in 9-year-old child with posterior urethral valves. Attempts at hydrostatic dilation were unsuccessful.
of dialysis and its attendant heparinization in the first 24 hours postoperatively. Pre-transplant nephrectomy. Indications generally accepted for pre-transplant nephrectomy include chronic pyelonephritis, gross vesicoureteral reflux (requires nephroureterectomy), renal calculi (large or associated with infection), poorly controlled hypertension, hydronephrosis, bilateral renal malignancy, immunologically active renal disease (that is Goodpasture's), in-
tractable severe proteinuria with hypoproteinemia, polycystic disease if associated with infection or hemorrhage, dialysis syndrome of cachexia, ascites and hypertension, and cutaneous urinary diversion (requires nephroureterectomy). However, it may be difficult to decide if nephrectomy is warranted. This difficulty is particularly true when suboptimally controlled hypertension is the only indication. Often these patients may only require more vigorous dialysis. Other areas of controversy include grade 1 vesicoureteral reflux or a small calculus, not associated with obstruction or infection. These indications probably are not strong for nephrectomy. It is important to keep in mind that significant morbidity and mortality have been associated with this procedure, particularly in older patients. In a recent review by Yarimizu and associates the mortality rate of bilateral nephrectomy for patients >50 years old was 11.1 per cent. 4 Careful perioperative cardiovascular monitoring, including a Swan Ganz or central venous catheter, appears to be important in this age group. An over-all mortality rate of 4 to 5 per cent and postoperative morbidity related to pulmonary problems, wound infection and loss of vascular access have been associated with pre-transplant nephrectomy. The choice of incision is based on the size of the kidneys, the possible need for performing nephroureterectomies and whether additional operations, such as vagotomy/pyloroplasty, splenectomy or conduit construction, are required. Unilateral ipsilateral nephrectomy at the time of transplantation may be a satisfactory alternative when the indication is severe proteinuria. Minimal extension of the retroperitoneal transplant incision is required. At least a 4-week interval between nephrectomies and transplantation is anticipated and at least 6 weeks if any intestinal procedure was coincidentally accomplished. Splenectomy. Whether routine splenectomy is indicated for those patients undergoing pre-transplant nephrectomy is controversial. We do consider splenectomy for those with persistent leukopenia, often associated with dialysis-acquired hypersplenism. 5 Prophylactic antibiotics and/or a pneumococcal vaccine is a consideration postoperatively in these patients, particularly infants and young children. The increased risk of bacterial
UROLOGICAL EVALUATION AND MANAGEMENT OF RENAL TRANSPLANT DONORS AND RECIPIENTS
sepsis is now well accepted. Intestinal conduit. Colon or ileal conduit may be positioned in several ways relative to the anticipated location of the allograft (fig. 3). 1 Our preference has been to place a sigmoid colon conduit opposite the side of the anticipated transplant site, with the base directed toward the allograft (fig. 4). During the last 2 years we have used sigmoid colon conduit drainage for 2 pediatric transplant patients and both patients are doing well. One of these has an antirefluxing tunnel and the other does not. In the latter case it was thought that bleeding from the transected transplant ureter was less than optimal, so it was elected not to compress it within a tunnel. When colon rather than ileum is used for the conduit, in addition to having the option to create an antirefluxing ureterointestinal anastomosis, we prefer the colon stoma to that of ileum. There is minimal angulation of the ureter if the conduit is placed opposite the side of the transplant and a sufficient length of transplant ureter remains so that a salvage cutaneous ureterostomy might be possible should the ureterointestinal anastomosis break down. Amin and associates have used primarily a terminal loop cutaneous ureterostomy in several transplant patients with satisfactory results. 6 We are reluctant to use normal caliber ureters for elective cutaneous ureterostomy. Use of an antirefluxing ureterointestinal anastomosis with the sigmoid conduit is optional but is particularly desirable if the patient may be a candidate for undiversion in the future.
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FIG. 4. Sigmoid colon conduit placed in left lower quadrant, opposite side of transplant.
EVALUATION OF LIVING RELATED KIDNEY DONOR
The use of living related donor kidneys as a source for transplantation is extremely important. A much better graft survival is realized and the recipient mortality rate is decreased by approximately 50 per cent. 7 The donor is faced with an extremely low mortality and long-term complication rate, and the loss of a kidney does not affect longevity in the great majority of cases.8 • 9 Short-term complications are not uncommon and often can be prevented. While striving to achieve the best possible result for our recipient we are mindful that our primary respol).sibility is to
FIG. 3. A, transplantation into dependent ileal loop. B, transplantation into opposite side of J?elvis as alternative to higher implantation. Reprinted with permission.
the donor and his immediate family. The donor should be healthy, have normal renal function and be free of urological disease. He must be freely willing to donate and not merely submitting to extreme family pressure to do so. Tentative donor selection is made by selecting from family members those who are free of any systemic disease, who are blood type ABO compatible and who usually have the most matching HLA antigens. Rh factor compatibility does not appear to be significant in renal transplantation. Minors generally are not considered for a number of reasons, not the least of which are the legal restrictions and requirements in most states. The potential donor receives extensive studies, including blood (blood urea nitrogen, creatinine values, uric acid, electrolytes, phosphate, calcium, fasting blood glucose, 2-hour glucose, serum glutamic oxaloacetic transaminase, alkaline phosphatase, complete blood count, prothrombin time and partial thromboplastin time), urine (creatinine clearance (2), urinalysis, urine culture, 24-hour protein and calcium) and radiology (IVP, chest x-ray and renal arteriogram). Other studies involve purified protein derivative skin test, electrocardiogram, immunological studies and serial blood pressure determinations. Occasionally indicated studies include renal scan/renogram, pulmonary functions, psychiatric consultation and glucose tolerance test. Economic considerations also may be important since in some areas reimbursement from Medicare may be more predictable if the donor evaluation is obtained in the same hospital in which the transplant is to be performed. An IVP is obtained before or the morning of admission to the hospital to exclude the possibility of a solitary kidney or other abnormality that would preclude donation. After all laboratory and clinical findings are reviewed additional studies or consultations may be indicated. The final study in the evaluation is an aortogram to assess the renal vasculature. This study is undertaken only after the decision has been made that this individual will be the donor. If any aspect of the urological history, physical examination, laboratory studies or radiographic findings suggests the potential for urologic disease then thorough urological investigation is imperative so that the patient's potential for future renal deterioration can be most fully understood. Medicolegally, there are some donor situations that deserve individual mention. Siblings and children of diabetic and polycystic recipients may later suffer these diseases themselves. If
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the glucose tolerance test is entirely normal and the diabetic's management considerations are worth emphasis. An intraoperpotential donor strongly desires to donate (while knowing he is ative diuresis is ensured with liberal intravenous fluids and 25 still at risk to develop the disease) we will consider them for to 50 gm. mannitol. Minimum traction is placed on the kidney nephrectomy. In polycystic disease unilateral nephrectomy will . to prevent renal vasospasm. This malady is manifested by little almost certainly hasten the onset of clinical renal failure. An urine flow from the transected ureter and a softening of the IVP with tomography and renal angiography probably can kidney. It is important not to clamp the vessels until this has elucidate this disease in the majority of patients >30 years old. resolved and a brisk flow of urine is re-established. We have Urine concentrating tests also may be helpful. In general, waited as long as 30 minutes for the kidney to recover. The relatives of polycystic patients <30 years old should be discour- pedicle is inspected carefully to ensure it is free from compresaged from donating. Carefully written informed consent is par- sion or torsion. After 30 minutes of oliguria it may be best to ticularly important in situations such as these. complete the nephrectomy, since rare instances of arterial inAn additional consideration concerns the children of the timal traction injuries have been reported. Excessive hilar disyoung parent who is about to donate to a sibling or parent. section is avoided. Inquiries should be made as to the past and present health of Renal vein length. A short renal vein is perhaps the most the children. If a history of obvious nephritis, failure to thrive, frustrating technical problem in kidney implantation. Obtaining urological problems or diabetes is obtained then the transplant a maximal vein length is important and usually requires a cuff should be deferred briefly until the medical situation is clarified. of vena cava with removal of the right kidney. Renal artery length. Artery length usually is not a problem If significant disease is found the potential donor's child could be studied as well. Then if the child and parent were ABO but occasionally the diameter of the renal artery decreases incompatible or if the child had cytotoxic antibodies to his markedly 1 or 2 cm. from the aorta. A longer artery may offset parent's lymphocytes (a positive cross-match) transplantation the problem of a relatively short ureter by allowing the graft to could proceed as planned with the donor knowing his child be placed lower on the iliac vein for those who exclusively use would not later be denied what might have been his only ureteroneocystostomy (fig. 5). A pyeloureterostomy, using donor pelvis and recipient ureter, is preferred when the ureter is compatible, living donor. During the donor evaluation we openly discuss morbidity considerably shorter than desired. and mortality of donor nephrectomy with the patient. These Ureteral length. Care should be taken to divide the ureter at patients frequently are much more anxious than their affect or below the level of the iliac vessels since a short ureter may and behavior suggest. They are concerned about the donor necessitate a deviation from the standard technique used for evaluation studies, the nature and risk of nephrectomy, as well ureteral implantation. Redundant ureter beyond that needed as the expected length of postoperative convalescence. Much of for ureteroneocystostomy is discarded to prevent angulation this anxiety is dispelled by thorough and candid physician and, hopefully, to minimize later fibrosis associated with urecounseling at the time of the evaluation. Pneumothorax, pneumonitis and atelectasis are the most common complications after donor nephrectomy. Of 60 donor nephrectomies done at our medical center since January 1974 11 patients had pulmonary complications. 10 Five had pneumothorax requiring tube thoracostomy and 6 had postoperative fever of > 101 attributed to atelectasis. Also included in this group were 1 wound infection, 2 urinary tract infections and 5 patients who required transfusion. In our total donor group of > 100 subjects we have 1 longterm complication. This occurred in a patient whose nephrectomy was performed via a transperitoneal approach because of multiple renal arteries. He subsequently has required surgical intervention for small bowel obstruction. Others have reported a few instances of renal deterioration owing to infections or calculous disease. Similarly, infrequent major complications, such as myocardial infarction and pulmonary emboli, have occurred. There have been 5 deaths owing to donor nephrectomy reported. Yet our experience is similar to most centers in that we have had no mortalities, with long-term complications being uncommon. In Harrison and Bennett's series of >350 donors they had 1 death.a This death occurred in a 72-year-old patient in whom hepatitis developed. Of their donors 14 per cent were >60 years old.a Until dramatic improvement occurs in the success of cadaver renal transplantation we will use living donors whenever possible. We believe that we can reassure potential donors with the knowledge that the odds of a safe recovery and minimal chance for long-term disability are overwhelmingly in their favor. Careful donor selection and evaluation, along with anticipation and prevention of postoperative pulmonary problems, are essential to sustain the acceptability of this procedure. LIVING RELATED DONOR NEPHRECTOMY
The donor receives overnight intravenous hydration with at least 2 1. half normal saline the evening before the operation. This hydration will facilitate diuresis and decrease the likelihood of hypotension with the anesthetic induction. There are numerous satisfactory approaches to this procedure but certain
Fm. 5. Post-transplant IVP in which kidney was placed lower in pelvis to accommodate relatively short ureter. Patient noted no pathological voiding symptoms despite renal impression against bladder.
UROLOGICAL EVALUATION AND MANAGEMENT OF RENAL TRANSPLANT DONORS AND RECIPIENTS
teral devascularization. These statements are not applicable to the smaller number of centers that prefer pyeloureterostomy to ureteroneocystostomy. Pyeloureterostomy is a satisfactory procedure but it necessitates ipsilateral nephrectomy and has been associated with a much higher incidence of urinary extravasation.11' 12 Ureteroneocystostomy has fewer acute postoperative sequelae but has a higher incidence of chronic hydronephrosis. This problem may be obviated by not stripping the ureter of its investing vascular connective tissue during nephrectomy. Divided polar artery. This problem rarely occurs unintentim,ally during living related donor nephrectomy. If divided near the aorta, as is often done electively in situations in which donors have bilateral multiple arteries, it usually is easily reparable (fig. 6). It is essential to perfuse this vessel and its associated segment as soon as possible after transection, just as with the main renal artery. If it is too short or otherwise not suitable for vascular repair then simple ligation is performed if it supplies a small portion of the kidney. If > 10 to 15 per cent of the kidney is involved then partial nephrectomy is advisable. Loss of a lower polar artery occasionally is associated with ureteral necrosis and fistula. After nephrectomy the kidney is perfused immediately with a chilled hyperosmolar solution. Failure of immediate function with a living related allograft is unusual unless it was not diuresing at the time of nephrectomy or if there was an excessive amount of warm ischemia time used for the anastomoses. Other less common etiologies of non-function include hyperacute rejection and anastomotic failure. Intraoperative hemorrhage requiring transfusion is an important preventable complication. With rare exception hemorrhage owing to losing control of an artery usually is brief because the arterial stump or aortic ostium is accessible by clamping or compression. On the other hand, the retracting renal vein stump can be elusive and a formidable surgical challenge. Wilford Hall's chief residents perform this procedure under careful staff supervision. Our training technique to prevent vena caval or renal vein hemorrhage is 1) to ratchet the Satinsky vascular clamp down to the last interdigitation, 2) to use curved scissors to divide the vein within this curved clamp rather than making several straight venotomies that often requires manipulating the clamp and 3) to have in reserve a Satinsky clamp just larger
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than the one applied to the vena cava. This is useful if the vena cava becomes tense (usually with retractor relaxation after removal of the kidney) and the vein begins to pull out of the clamp. It is considerably easier to apply the larger clamp behind the primary one rather than using a multiple clamp technique. DONOR CADA VER NEPHRECTOMY
This source of grafts is used in >70 per cent of the potential recipients. Across the country there are hundreds of patients waiting for kidneys. The problem is not with surgeons being unavailable to remove them but much more related to factors such as 1) family reluctance to agree to donation, 2) county medical examiner's reluctance to release certain types of injuries for organ donation and 3) the delay or failure of the primary physician to consider his patient as a possible organ donor. Subconsciously, the potential medicolegal ramifications and wasted time with the administrative responsibilities associated with obtaining consent and coroner clearance for organ donation may dampen one's perception of a potential donor. This need not be such a burden. In many communities, including our own, there is an organ bank or transplantation program that will physically assist the primary physician with the administrative problems, although they are restricted from giving primary patient care. The most important step in organ retrieval is to identify the apparently acceptable donor. The availability of an informed opinion in this regard from the local urologist could make all the difference as to whether the primary physician will consider his patient for possible organ donation. Reasonable criteria to aid in identifying an apparently unacceptable potential donor include 1) age (newborns or >55 years old), 2) prolonged warm ischemia (>1 hour), 3) generalized infection (dying of sepsis or abdominal sepsis, with possible exceptions of pneumonitis or positive urine culture), 4) preexisting diseases (hypertension unrelated to cardiovascular accident this admission, diabetes, collagen disease and malignancy other than central nervous system) and 5) marked azotemiaserum creatinine >3.0 (unless dramatically improved within a few hours with diuretics and hydration). 13 Use of the heartbeating donors is desirable whenever possible, in strict accord with local brain death criteria. There are several satisfactory approaches in performing cadaver donor nephrectomy. 14- 17 Many of the principles involved are the same as those discussed with living related donor nephrectomy. In most large communities a relatively stan.dardized protocol is used to ensure as much as possible a good quality cadaver kidney for distribution or local use. REFERENCES
FIG. 6. Anastomosis of transected upper pole renal artery to main renal artery relative to remainder of implantation.
I. Peters, P. C.: The management of renal transplant recipients with abnormal lower urinary tract-reconstruction versus diversion. Urol. Clin. N. Amer., 3: 685, 1976. 2. Firlit, C. F.: Renal transplantation. In: Clinical Pediatric Urology. Edited by P. P. Kelalis and L. R. King. Philadelphia: W.B. Saunders Co., vol. 2, pp. 811-820, 1976. 3. Shenasky, J. H., II: Renal transplantation in patients with urologic abnormalities. J. Urol., 115: 490, 1976. 4. Yarimizu, S. N., Susan, L. P., Straffon, R. A., Stewart, B. H., Magnusson, M. 0. and Nakamoto, S.S.: Mortality and morbidity in pretransplant bilateral nephrectomy. Analysis of 305 cases. Urology, 12: 55, 1978. 5. Banowsky, L. H.: The role of adjuvant operations in renal transplantation. Urol. Clin. N. Amer., 3: 527, 1976. 6. Amin, M., Howerton, L. W. and Lich, R., Jr.: Terminal loop cutaneous ureterostomy: a method of urinary drainage in kidney transplantation. J. Urol., 118: 379, 1977. 7. Rapaport, F. T., Converse, J. M. and Billingham, R. E.: Recent advances in clinical experimental transplantation. J.A.M.A., 237: 2835, 1977. 8. Harrison, J. H. and Bennett, A. H.: The familial living donor in renal transplantation. J. Urol., 118: 166, 1977. 9. Jacobs, S. C., McLaughlin, A. P., III, Halasz, N. H. and Gittes, R. F.: Live donor nephrectomy. Urology, 5: 175, 1975.
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10. Turlington, J. T., Weber, C. H. and Montie, J.: Living related donors at USAF Wilford Hall Medical Center. Proceedings of the Kimbrough Urological Seminar. Edited by H. G. Stevenson. New York: Morton-Norwich Products, Inc., vol. XI, p. 257, 1978. 11. Libertino, J. A. and Zinman, L.: Renal transplantation. In: Pediatric and Adult Reconstructive Urologic Surgery. Baltimore: The Williams & Wilkins Co., pp. 81-94, 1977. 12. Smith, R. B. and Ehrlich, R. M.: Complications of renal transplant surgery (including autotransplantation). In: Complications of Urologic Surgery. Prevention and Management. Edited by R. B. Smith and D. G. Skinner. Philadelphia: W. B. Saunders Co., pp. 459-498, 1976.
13. Belzer, F. 0. and Kountz, S. L.: Criteria for selection of cadaver donors. Transplant. Proc., 4: 591, 1972. 14. Salvatierra, 0., Jr., Olcott, C., IV, Cochrum, K. C., Amend, W. J., Jr. and Feduska, N. J.: Procurement of cadaver kidneys. Urol. Clin. N. Amer., 3: 457, 1976. 15. Linke, C. A., Linke, C. L., Davis, R. S. and Fridd, C. W.: Cadaver donor nephrectomy. Urology, 6: 133, 1975. 16. Merkel, F. K., Jonasson, 0. and Bergan, J. J.: Procurement of cadaver donor organs: evisceration technique. Transplant. Proc., 4: 585, 1972. 17. Martin, D. C.: Nephrectomy. Urology, suppl. 1, 10: 11, 1977.
Vol. 124, September
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1980 by The Williams & Wilkins Co.
Review Article THE UROLOGICAL EVALUATION AND MANAGEMENT OF RENAL TRANSPLANT DONORS AND RECIPIENTS DAVID J. CONFER*
LYNN H. BANOWSKY
AND
From the Departments of Urology and Renal Transplantation, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base and University of Texas Health Science Center, San Antonio, Texas
Currently, Medicare is underwriting the expense for approximately 35,000 patients receiving hemodialysis. This figure was 14,000 in 1972 and is projected to reach 60,000 by 1983. Considering the increased willingness to transplant relatively high risk patients, coupled with the ever increasing number of renal failure survivors, we can expect more renal transplants to be done and even more need for urological evaluation of potential renal transplant donors and recipients. TRANSPLANT RECIPIENT EVALUATION
The evaluation of potential transplant recipients is an extensive investigation to uncover any physical or emotional defect that might preclude successful transplantation. A complete history is obtained and physical examination is accomplished. Potential sources of infection and possible malignancies must be discovered, since these may be of devastating consequences to the immunosuppressed, post-transplant patient. Peptic ulcer disease and diverticulitis are relative contraindications to transplantation, unless surgically manageable before transplantation. Consultations for ears, nose, throat and oral surgery are necessary to exclude potential upper respiratory and oropharyngeal sources of infection. A Papanicolaou smear is obtained routinely on all women. Extensive screening laboratory studies are obtained. Proteinuria is quantitated. Lower gastrointestinal studies are obtained on patients >40 years old. Most chronic renal failure patients are hypertensive and the ease of control of this hypertension with adequate dialysis and small amounts of medication is assessed. The patient is scrutinized carefully for a history of urinary tract infection. Neurological and psychological studies are included. Urological evaluation is individualized, often depending on historical factors. If the patient has no history of infections or calculi, or symptoms of voiding dysfunction a voiding cystourethrogram often will be the only diagnostic study needed. Urine for culture is obtained at the time of this catheterization. A history of infection or calculi obligates one to visualize the upper collecting systems, usually by retrograde pyelography. If a possible anatomical source of infection is found pre-transplant nephrectomy will be necessary. Patients with cutaneous diversion, diabetes, pathological voiding symptoms, history of urinary tract infections or calculi, or other evidence of voiding dysfunction receive a thorough lower urinary tract evaluation. These studies include 1) voiding cystourethrogram, 2) cystoscopy and 3) cystometric evaluation with urethral pressure profile and anal or perinea! electromyogram as indicated. Uroflowmetric studies are useful. Peters has reviewed parameters for selecting those patients with satisfactory bladder function in a number of interesting clinical situations. 1 Any urological pro* Requests for reprints: Department of Urology/SGHSU, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas 78236. The views expressed herein are those of the authors and do not necessarily reflect the views of the United States Air Force.
cedure needed to ensure adequate voiding capability, such as a urethroplasty or prostatectomy, is performed well in advance of transplantation. Often defunctionalized bladders are satisfactory, particularly in those patients whose primary disease had been posterior urethral valves. These small bladders may dilate to satisfactory size within a few months. 1• 2 Figure 1, A demonstrates the apparent bladder capacity on cystography of a 17pound, 2-year-old child before transplantation but after valve resection. Figure 1, B shows the extent of bladder enlargement apparent on excretory urography (IVP) 6 weeks after receipt of his mother's kidney. Occasionally, there is uncertainty as to whether the bladder will be adequate for transplantation. This uncertainty is particularly true when the bladder is small and severely trabeculated (fig. 2). Shenasky suggested weekly hydrodilation for a few months in such patients to gain insight as to the distensibility of these bladders. 3 Information regarding continence and the ability to empty also will be useful. 3 Nonetheless, there will be instances in which satisfactory bladder function cannot be assured. In this situation we agree with Peters 1 and others that a satisfactory ileal or colon conduit should be constructed at least 6 weeks before transplantation. A ureterointestinal anastomosis that prevents reflux is desirable. The bilateral nephroureterectomy necessary in those with ureterostomies may be combined with conduit construction. In children with cutaneous diversions these should be studied to eliminate the possibility of stomal stenosis or other obstructive phenomena. Occasionally, dramatic improvement in renal function can be realized with improved drainage. This is particularly beneficial in small children in whom delaying transplantation for 1 or 2 years might allow enough growth for them to receive a related adult allograft rather than requiring a pediatric cadaver kidney. Generally, we do not consider cystectomy for pediatric diversion patients in whom there is a possibility for undiversion in the future, unless persistent lower urinary tract infections are anticipated. This is particularly important with the continual improvement in anti-incontinence procedures. COMPREHENSIVE SURGICAL MANAGEMENT OF RECIPIENT
Vascular access. With the exception of small children most prospective recipients have vascular access for dialysis. These are either external arteriovenous shunts, such as Scribner's shunt, or internal (subcutaneous) arteriovenous fistulas. Shunts have the advantage of immediate use, whereas it is best to wait several weeks to use a fistula. However, fistulas have more likelihood oflong-term patency and less risk of infection. A few centers use peritoneal dialysis routinely, particularly for patients with diabetes mellitus. In our adults satisfactory fistulas are created well ahead of the anticipated dialysis and operation. In children in whom access loss owing to thrombosis is more of a problem this is accomplished in a minimal interval before nephrectomies or transplantation. In general, dialysis on 2 of the 3 days before the operation will minimize the requirement
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FIG. 1. A, apparent small size of bladder after transurethral resection of posterior urethral valves in 2-year-old child before transplantation (maximum filling on high pressure cystogram). B, relative enlargement of defunctionalized bladder noted in part A demonstrated on IVP 6 weeks after transplantation. Fluoroscopy demonstrated complete emptying of ureter without obstruction.
FIG. 2. Small, thickened, trabeculated bladder with capacity of 15 cc in 9-year-old child with posterior urethral valves. Attempts at hydrostatic dilation were unsuccessful.
of dialysis and its attendant heparinization in the first 24 hours postoperatively. Pre-transplant nephrectomy. Indications generally accepted for pre-transplant nephrectomy include chronic pyelonephritis, gross vesicoureteral reflux (requires nephroureterectomy), renal calculi (large or associated with infection), poorly controlled hypertension, hydronephrosis, bilateral renal malignancy, immunologically active renal disease (that is Goodpasture's), in-
tractable severe proteinuria with hypoproteinemia, polycystic disease if associated with infection or hemorrhage, dialysis syndrome of cachexia, ascites and hypertension, and cutaneous urinary diversion (requires nephroureterectomy). However, it may be difficult to decide if nephrectomy is warranted. This difficulty is particularly true when suboptimally controlled hypertension is the only indication. Often these patients may only require more vigorous dialysis. Other areas of controversy include grade 1 vesicoureteral reflux or a small calculus, not associated with obstruction or infection. These indications probably are not strong for nephrectomy. It is important to keep in mind that significant morbidity and mortality have been associated with this procedure, particularly in older patients. In a recent review by Yarimizu and associates the mortality rate of bilateral nephrectomy for patients >50 years old was 11.1 per cent. 4 Careful perioperative cardiovascular monitoring, including a Swan Ganz or central venous catheter, appears to be important in this age group. An over-all mortality rate of 4 to 5 per cent and postoperative morbidity related to pulmonary problems, wound infection and loss of vascular access have been associated with pre-transplant nephrectomy. The choice of incision is based on the size of the kidneys, the possible need for performing nephroureterectomies and whether additional operations, such as vagotomy/pyloroplasty, splenectomy or conduit construction, are required. Unilateral ipsilateral nephrectomy at the time of transplantation may be a satisfactory alternative when the indication is severe proteinuria. Minimal extension of the retroperitoneal transplant incision is required. At least a 4-week interval between nephrectomies and transplantation is anticipated and at least 6 weeks if any intestinal procedure was coincidentally accomplished. Splenectomy. Whether routine splenectomy is indicated for those patients undergoing pre-transplant nephrectomy is controversial. We do consider splenectomy for those with persistent leukopenia, often associated with dialysis-acquired hypersplenism. 5 Prophylactic antibiotics and/or a pneumococcal vaccine is a consideration postoperatively in these patients, particularly infants and young children. The increased risk of bacterial
UROLOGICAL EVALUATION AND MANAGEMENT OF RENAL TRANSPLANT DONORS AND RECIPIENTS
sepsis is now well accepted. Intestinal conduit. Colon or ileal conduit may be positioned in several ways relative to the anticipated location of the allograft (fig. 3). 1 Our preference has been to place a sigmoid colon conduit opposite the side of the anticipated transplant site, with the base directed toward the allograft (fig. 4). During the last 2 years we have used sigmoid colon conduit drainage for 2 pediatric transplant patients and both patients are doing well. One of these has an antirefluxing tunnel and the other does not. In the latter case it was thought that bleeding from the transected transplant ureter was less than optimal, so it was elected not to compress it within a tunnel. When colon rather than ileum is used for the conduit, in addition to having the option to create an antirefluxing ureterointestinal anastomosis, we prefer the colon stoma to that of ileum. There is minimal angulation of the ureter if the conduit is placed opposite the side of the transplant and a sufficient length of transplant ureter remains so that a salvage cutaneous ureterostomy might be possible should the ureterointestinal anastomosis break down. Amin and associates have used primarily a terminal loop cutaneous ureterostomy in several transplant patients with satisfactory results. 6 We are reluctant to use normal caliber ureters for elective cutaneous ureterostomy. Use of an antirefluxing ureterointestinal anastomosis with the sigmoid conduit is optional but is particularly desirable if the patient may be a candidate for undiversion in the future.
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'11
FIG. 4. Sigmoid colon conduit placed in left lower quadrant, opposite side of transplant.
EVALUATION OF LIVING RELATED KIDNEY DONOR
The use of living related donor kidneys as a source for transplantation is extremely important. A much better graft survival is realized and the recipient mortality rate is decreased by approximately 50 per cent. 7 The donor is faced with an extremely low mortality and long-term complication rate, and the loss of a kidney does not affect longevity in the great majority of cases.8 • 9 Short-term complications are not uncommon and often can be prevented. While striving to achieve the best possible result for our recipient we are mindful that our primary respol).sibility is to
FIG. 3. A, transplantation into dependent ileal loop. B, transplantation into opposite side of J?elvis as alternative to higher implantation. Reprinted with permission.
the donor and his immediate family. The donor should be healthy, have normal renal function and be free of urological disease. He must be freely willing to donate and not merely submitting to extreme family pressure to do so. Tentative donor selection is made by selecting from family members those who are free of any systemic disease, who are blood type ABO compatible and who usually have the most matching HLA antigens. Rh factor compatibility does not appear to be significant in renal transplantation. Minors generally are not considered for a number of reasons, not the least of which are the legal restrictions and requirements in most states. The potential donor receives extensive studies, including blood (blood urea nitrogen, creatinine values, uric acid, electrolytes, phosphate, calcium, fasting blood glucose, 2-hour glucose, serum glutamic oxaloacetic transaminase, alkaline phosphatase, complete blood count, prothrombin time and partial thromboplastin time), urine (creatinine clearance (2), urinalysis, urine culture, 24-hour protein and calcium) and radiology (IVP, chest x-ray and renal arteriogram). Other studies involve purified protein derivative skin test, electrocardiogram, immunological studies and serial blood pressure determinations. Occasionally indicated studies include renal scan/renogram, pulmonary functions, psychiatric consultation and glucose tolerance test. Economic considerations also may be important since in some areas reimbursement from Medicare may be more predictable if the donor evaluation is obtained in the same hospital in which the transplant is to be performed. An IVP is obtained before or the morning of admission to the hospital to exclude the possibility of a solitary kidney or other abnormality that would preclude donation. After all laboratory and clinical findings are reviewed additional studies or consultations may be indicated. The final study in the evaluation is an aortogram to assess the renal vasculature. This study is undertaken only after the decision has been made that this individual will be the donor. If any aspect of the urological history, physical examination, laboratory studies or radiographic findings suggests the potential for urologic disease then thorough urological investigation is imperative so that the patient's potential for future renal deterioration can be most fully understood. Medicolegally, there are some donor situations that deserve individual mention. Siblings and children of diabetic and polycystic recipients may later suffer these diseases themselves. If
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the glucose tolerance test is entirely normal and the diabetic's management considerations are worth emphasis. An intraoperpotential donor strongly desires to donate (while knowing he is ative diuresis is ensured with liberal intravenous fluids and 25 still at risk to develop the disease) we will consider them for to 50 gm. mannitol. Minimum traction is placed on the kidney nephrectomy. In polycystic disease unilateral nephrectomy will . to prevent renal vasospasm. This malady is manifested by little almost certainly hasten the onset of clinical renal failure. An urine flow from the transected ureter and a softening of the IVP with tomography and renal angiography probably can kidney. It is important not to clamp the vessels until this has elucidate this disease in the majority of patients >30 years old. resolved and a brisk flow of urine is re-established. We have Urine concentrating tests also may be helpful. In general, waited as long as 30 minutes for the kidney to recover. The relatives of polycystic patients <30 years old should be discour- pedicle is inspected carefully to ensure it is free from compresaged from donating. Carefully written informed consent is par- sion or torsion. After 30 minutes of oliguria it may be best to ticularly important in situations such as these. complete the nephrectomy, since rare instances of arterial inAn additional consideration concerns the children of the timal traction injuries have been reported. Excessive hilar disyoung parent who is about to donate to a sibling or parent. section is avoided. Inquiries should be made as to the past and present health of Renal vein length. A short renal vein is perhaps the most the children. If a history of obvious nephritis, failure to thrive, frustrating technical problem in kidney implantation. Obtaining urological problems or diabetes is obtained then the transplant a maximal vein length is important and usually requires a cuff should be deferred briefly until the medical situation is clarified. of vena cava with removal of the right kidney. Renal artery length. Artery length usually is not a problem If significant disease is found the potential donor's child could be studied as well. Then if the child and parent were ABO but occasionally the diameter of the renal artery decreases incompatible or if the child had cytotoxic antibodies to his markedly 1 or 2 cm. from the aorta. A longer artery may offset parent's lymphocytes (a positive cross-match) transplantation the problem of a relatively short ureter by allowing the graft to could proceed as planned with the donor knowing his child be placed lower on the iliac vein for those who exclusively use would not later be denied what might have been his only ureteroneocystostomy (fig. 5). A pyeloureterostomy, using donor pelvis and recipient ureter, is preferred when the ureter is compatible, living donor. During the donor evaluation we openly discuss morbidity considerably shorter than desired. and mortality of donor nephrectomy with the patient. These Ureteral length. Care should be taken to divide the ureter at patients frequently are much more anxious than their affect or below the level of the iliac vessels since a short ureter may and behavior suggest. They are concerned about the donor necessitate a deviation from the standard technique used for evaluation studies, the nature and risk of nephrectomy, as well ureteral implantation. Redundant ureter beyond that needed as the expected length of postoperative convalescence. Much of for ureteroneocystostomy is discarded to prevent angulation this anxiety is dispelled by thorough and candid physician and, hopefully, to minimize later fibrosis associated with urecounseling at the time of the evaluation. Pneumothorax, pneumonitis and atelectasis are the most common complications after donor nephrectomy. Of 60 donor nephrectomies done at our medical center since January 1974 11 patients had pulmonary complications. 10 Five had pneumothorax requiring tube thoracostomy and 6 had postoperative fever of > 101 attributed to atelectasis. Also included in this group were 1 wound infection, 2 urinary tract infections and 5 patients who required transfusion. In our total donor group of > 100 subjects we have 1 longterm complication. This occurred in a patient whose nephrectomy was performed via a transperitoneal approach because of multiple renal arteries. He subsequently has required surgical intervention for small bowel obstruction. Others have reported a few instances of renal deterioration owing to infections or calculous disease. Similarly, infrequent major complications, such as myocardial infarction and pulmonary emboli, have occurred. There have been 5 deaths owing to donor nephrectomy reported. Yet our experience is similar to most centers in that we have had no mortalities, with long-term complications being uncommon. In Harrison and Bennett's series of >350 donors they had 1 death.a This death occurred in a 72-year-old patient in whom hepatitis developed. Of their donors 14 per cent were >60 years old.a Until dramatic improvement occurs in the success of cadaver renal transplantation we will use living donors whenever possible. We believe that we can reassure potential donors with the knowledge that the odds of a safe recovery and minimal chance for long-term disability are overwhelmingly in their favor. Careful donor selection and evaluation, along with anticipation and prevention of postoperative pulmonary problems, are essential to sustain the acceptability of this procedure. LIVING RELATED DONOR NEPHRECTOMY
The donor receives overnight intravenous hydration with at least 2 1. half normal saline the evening before the operation. This hydration will facilitate diuresis and decrease the likelihood of hypotension with the anesthetic induction. There are numerous satisfactory approaches to this procedure but certain
Fm. 5. Post-transplant IVP in which kidney was placed lower in pelvis to accommodate relatively short ureter. Patient noted no pathological voiding symptoms despite renal impression against bladder.
UROLOGICAL EVALUATION AND MANAGEMENT OF RENAL TRANSPLANT DONORS AND RECIPIENTS
teral devascularization. These statements are not applicable to the smaller number of centers that prefer pyeloureterostomy to ureteroneocystostomy. Pyeloureterostomy is a satisfactory procedure but it necessitates ipsilateral nephrectomy and has been associated with a much higher incidence of urinary extravasation.11' 12 Ureteroneocystostomy has fewer acute postoperative sequelae but has a higher incidence of chronic hydronephrosis. This problem may be obviated by not stripping the ureter of its investing vascular connective tissue during nephrectomy. Divided polar artery. This problem rarely occurs unintentim,ally during living related donor nephrectomy. If divided near the aorta, as is often done electively in situations in which donors have bilateral multiple arteries, it usually is easily reparable (fig. 6). It is essential to perfuse this vessel and its associated segment as soon as possible after transection, just as with the main renal artery. If it is too short or otherwise not suitable for vascular repair then simple ligation is performed if it supplies a small portion of the kidney. If > 10 to 15 per cent of the kidney is involved then partial nephrectomy is advisable. Loss of a lower polar artery occasionally is associated with ureteral necrosis and fistula. After nephrectomy the kidney is perfused immediately with a chilled hyperosmolar solution. Failure of immediate function with a living related allograft is unusual unless it was not diuresing at the time of nephrectomy or if there was an excessive amount of warm ischemia time used for the anastomoses. Other less common etiologies of non-function include hyperacute rejection and anastomotic failure. Intraoperative hemorrhage requiring transfusion is an important preventable complication. With rare exception hemorrhage owing to losing control of an artery usually is brief because the arterial stump or aortic ostium is accessible by clamping or compression. On the other hand, the retracting renal vein stump can be elusive and a formidable surgical challenge. Wilford Hall's chief residents perform this procedure under careful staff supervision. Our training technique to prevent vena caval or renal vein hemorrhage is 1) to ratchet the Satinsky vascular clamp down to the last interdigitation, 2) to use curved scissors to divide the vein within this curved clamp rather than making several straight venotomies that often requires manipulating the clamp and 3) to have in reserve a Satinsky clamp just larger
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than the one applied to the vena cava. This is useful if the vena cava becomes tense (usually with retractor relaxation after removal of the kidney) and the vein begins to pull out of the clamp. It is considerably easier to apply the larger clamp behind the primary one rather than using a multiple clamp technique. DONOR CADA VER NEPHRECTOMY
This source of grafts is used in >70 per cent of the potential recipients. Across the country there are hundreds of patients waiting for kidneys. The problem is not with surgeons being unavailable to remove them but much more related to factors such as 1) family reluctance to agree to donation, 2) county medical examiner's reluctance to release certain types of injuries for organ donation and 3) the delay or failure of the primary physician to consider his patient as a possible organ donor. Subconsciously, the potential medicolegal ramifications and wasted time with the administrative responsibilities associated with obtaining consent and coroner clearance for organ donation may dampen one's perception of a potential donor. This need not be such a burden. In many communities, including our own, there is an organ bank or transplantation program that will physically assist the primary physician with the administrative problems, although they are restricted from giving primary patient care. The most important step in organ retrieval is to identify the apparently acceptable donor. The availability of an informed opinion in this regard from the local urologist could make all the difference as to whether the primary physician will consider his patient for possible organ donation. Reasonable criteria to aid in identifying an apparently unacceptable potential donor include 1) age (newborns or >55 years old), 2) prolonged warm ischemia (>1 hour), 3) generalized infection (dying of sepsis or abdominal sepsis, with possible exceptions of pneumonitis or positive urine culture), 4) preexisting diseases (hypertension unrelated to cardiovascular accident this admission, diabetes, collagen disease and malignancy other than central nervous system) and 5) marked azotemiaserum creatinine >3.0 (unless dramatically improved within a few hours with diuretics and hydration). 13 Use of the heartbeating donors is desirable whenever possible, in strict accord with local brain death criteria. There are several satisfactory approaches in performing cadaver donor nephrectomy. 14- 17 Many of the principles involved are the same as those discussed with living related donor nephrectomy. In most large communities a relatively stan.dardized protocol is used to ensure as much as possible a good quality cadaver kidney for distribution or local use. REFERENCES
FIG. 6. Anastomosis of transected upper pole renal artery to main renal artery relative to remainder of implantation.
I. Peters, P. C.: The management of renal transplant recipients with abnormal lower urinary tract-reconstruction versus diversion. Urol. Clin. N. Amer., 3: 685, 1976. 2. Firlit, C. F.: Renal transplantation. In: Clinical Pediatric Urology. Edited by P. P. Kelalis and L. R. King. Philadelphia: W.B. Saunders Co., vol. 2, pp. 811-820, 1976. 3. Shenasky, J. H., II: Renal transplantation in patients with urologic abnormalities. J. Urol., 115: 490, 1976. 4. Yarimizu, S. N., Susan, L. P., Straffon, R. A., Stewart, B. H., Magnusson, M. 0. and Nakamoto, S.S.: Mortality and morbidity in pretransplant bilateral nephrectomy. Analysis of 305 cases. Urology, 12: 55, 1978. 5. Banowsky, L. H.: The role of adjuvant operations in renal transplantation. Urol. Clin. N. Amer., 3: 527, 1976. 6. Amin, M., Howerton, L. W. and Lich, R., Jr.: Terminal loop cutaneous ureterostomy: a method of urinary drainage in kidney transplantation. J. Urol., 118: 379, 1977. 7. Rapaport, F. T., Converse, J. M. and Billingham, R. E.: Recent advances in clinical experimental transplantation. J.A.M.A., 237: 2835, 1977. 8. Harrison, J. H. and Bennett, A. H.: The familial living donor in renal transplantation. J. Urol., 118: 166, 1977. 9. Jacobs, S. C., McLaughlin, A. P., III, Halasz, N. H. and Gittes, R. F.: Live donor nephrectomy. Urology, 5: 175, 1975.
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10. Turlington, J. T., Weber, C. H. and Montie, J.: Living related donors at USAF Wilford Hall Medical Center. Proceedings of the Kimbrough Urological Seminar. Edited by H. G. Stevenson. New York: Morton-Norwich Products, Inc., vol. XI, p. 257, 1978. 11. Libertino, J. A. and Zinman, L.: Renal transplantation. In: Pediatric and Adult Reconstructive Urologic Surgery. Baltimore: The Williams & Wilkins Co., pp. 81-94, 1977. 12. Smith, R. B. and Ehrlich, R. M.: Complications of renal transplant surgery (including autotransplantation). In: Complications of Urologic Surgery. Prevention and Management. Edited by R. B. Smith and D. G. Skinner. Philadelphia: W. B. Saunders Co., pp. 459-498, 1976.
13. Belzer, F. 0. and Kountz, S. L.: Criteria for selection of cadaver donors. Transplant. Proc., 4: 591, 1972. 14. Salvatierra, 0., Jr., Olcott, C., IV, Cochrum, K. C., Amend, W. J., Jr. and Feduska, N. J.: Procurement of cadaver kidneys. Urol. Clin. N. Amer., 3: 457, 1976. 15. Linke, C. A., Linke, C. L., Davis, R. S. and Fridd, C. W.: Cadaver donor nephrectomy. Urology, 6: 133, 1975. 16. Merkel, F. K., Jonasson, 0. and Bergan, J. J.: Procurement of cadaver donor organs: evisceration technique. Transplant. Proc., 4: 585, 1972. 17. Martin, D. C.: Nephrectomy. Urology, suppl. 1, 10: 11, 1977.