UROLOGICAL COMPLICATIONS OF RENAL TRANSPLANTATION1

By GRANT WILLIAMS, M.S., M.Sc., F.R.C.S., A. G. BIRTCH. M.D., R. E. WILSON, M.D., J. HARTWELL HARRISON, M.D., and J. E. MURRAY. M.D.

Fronl the Peter Bent Brighanl Hospital, Boston, MasJaclluJettJ

THE urological complications of renal transplantation have been recently reviewed (Prout et al., 1967; Al-Askari 1968; Palmer et a / . , 1969; Walsh, 1969). This communication is concerned with two particular complications, urinary extravasation and ureteric obstruction.

TABLE 1

Urological Complications of Renal Transplantations

A-EXTRAVASATION Pelvi-ureteric Anastomosis . I I Pyelostomy . . 2 Uretero-vesical Anastomosis . . 6 Other Vesical Leaks . . - Sloughing of Ureter . . . 4 Calyco-cutaneous . . 2

Uretero-vesical . . 4 Pelvi-ureteric . . 1

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B-OBSTRUCTION

A. Urinary Extravasation.-Walsh (1969) reported 3 cases of urinary extravasation out of 31 transplants (10 per cent.)-all of whom died. Palmer er a!. (1969) reported 6 urinary fistulz. out of their 36 transplants (17 per cent)-3 of whom died. Prout et al. (1967) reported 5 cases of urinary leakage and 2 cases of perivesical abscess out of their 93 cases-an incidence of 8 per cent. Two of these cases died as a direct result. Salaman et al. (1969) reported 7 cases of urinary fistula (10 per cent.)-2 of whom died.

Murray et af. (1968) reported 17 cases of ureteric fistula: out of 110 transplants performed at Peter Bent Brigham Hospital up to 1st February 1968, an incidence of 15 per cent.--one-third of these patients died as a direct cause of their urinary leakage. Since that report 48 further trans- plants have been performed and 6 further urinary leakages have occurred. Overall there have been 9 deaths attributable to extravasation in these 23 patients. Twenty-seven instances of extravasation are discussed in these 23 patients, 4 of whom had 2 fistula:. Two of these double fistulz included intractable pyelostomy leakage secondary to the nephrostomy used as a primary treatment. Twelve leakages were in cadaveric transplants, resulting in 3 deaths. Fifteen occurred in living donor transplants, resulting in 6 deaths.

1. Extravasation after Pelvi- Ureteric Anastomosis.-There were 1 1 cases of uretero-pelvic leakage. Five transplants were from related living donors, 3 from cadaveric donors, and 3 from so-called obligatory nephrectomies. Tissue typing was available for 3 of the related living donors which were all parent-to-child transplants. There were one or two major mismatches in each of these transplants.

The uretero-pelvic anastomoses were performed with chromic catgut, usually over a silastic stent. Nephrostomies were performed on 4 of the 1 1 at the time of transplantation.

1 Read at the Twenty-fifth Annual Meeting of the British Association of Urological Surgeons in London, June 1969.

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While a reduction in urinary output is usually due to rejection or acute tubular necrosis, it may be due to urinary extravasation which is not always accompanied by obvious leakage from the wound. In 3 cases the drop in urinary output seemed to be due to rejection. Two of these 3 patients had nephrostomies. After treatment of the " rejection " with highdose steroids, the urinary leakage occurred, two 7 and 18 days respectively, following the original oliguric episode. The other 8 uretero-pelvic fistula: occurred from 4 to 40 days after transplantation. Seven of these 11 patients heralded their urinary leakage with signs of infection, high temperatures, shaking chills, and positive blood cultures. Four of these 7 patients died of uncontrollable sepsis, and were the only patients in this group to die.

The management of all these patients was to re-establish drainage either by nephrostomy and wound drainage or by retrograde ureteric catheter. Attempts were made to repair 3 of the fistula, one at 13 days, one at 26 days and one at 3 months, but only one attempt was successful. The other 2 patients died of sepsis.

Drainage via an indwelling ureteric catheter was only once successful in these I 1 patients. Of these 11 uretero-pelvic leakages 7 were treated by nephrostomy and only one died. He

had a stricture at the site of the uretero-pelvic leakage, and died of septicremia following an attempted repair. Of the 4 patients who did not have nephrostomies, only one survived. Two of those who succumbed developed major sepsis and secondary hzmorrhage.

2. Extravasation after Uretero-Vesical Anastomosis.-Six patients had uretero-vesical extravasation. In 4 of the patients the leak was obvious within the first 5 days. In the sixth patient the leakage presumably occurred at an early stage, but presented as a mass in the left iliac fossa 2 months after transplantation. At exploration there was a huge infected extra-vesical collection of urine. The ureter had retracted so that there was a pin-hole ureteric orifice, presum- ably secondary to the extravasation and infection.

In 3 of these patients (2 of whom were septiczmic) the wound was laid widely open, and proximal drainage established with a nephrostomy. These nephrostomy sites took up to 3 months to heal.

In one patient the original extravasation was followed by sloughing of the ureter, which was satisfactorily treated by a Boari flap and temporary nephrostomy.

One patient who did not have a nephrostomy after extravasation was diagnosed, became septicremic and the kidney was removed for secondary hremorrhage. He survived this only to die of an unrelated problem.

A more satisfactory outcome was seen in the sixth patient, where early leakage was treated by immediate anastomosis of the donor renal pelvis to the recipient ureter.

3. Other Vesical Fistu1re.-Two other cases of vesical fistulae had an extremely stormy course. One from a cadaveric donor had suprapubic bladder drainage, following the uretero-

neocystostomy. Rejection episodes were treated with steroids, and this suprapubic fistula proved resistant to all attempts to close it. Abscess formation was followed by secondary hremorrhagc and transplant nephrectomy.

The other patient became oliguric on the fourth day after transplant and was explored after cystography demonstrated extravasation (Fig. 1). He was found to have a dehiscence of the detrusor muscle on the right lateral wall of the bladder, through which urine was leaking. The transplant ureter was also dilated and was re-implanted.

A covering nephrostomy was performed, but he continued to leak urine from the concurrent pyelotomy (Fig. 2). The wound was therefore widely laid open, the extravasation drained and secondary suture of the abdominal wall later performed. The nephrostomy was dry 3 months later (Fig. 5).

4. Extravasation after Primary Sloughing of the Ureter.-Four patients developed extravasa- tion following primary sloughing of the ureter.

One of these sloughed the proximal 2 in. of his own ureter 10 days after the initial uretero- pelvic anastomosis. The sloughed host ureter was resected and re-anastomosed to the renal

FIG. 1

Fig. 1.-Cystogram showing extravasation from side wa!l of

bladder.

Fig. 2.-Nephrostogram, one day post-operatively on patient in Figure 1, showing leaking from pyelotomy incision, and from the region of the re-im-

planted ureter.

Fig. 3.-Nephrostograrn. 2 weeks after Figure 2, showing the leak from the renal pelvis still present, dye outlining the

medial border of the kidney.

FIG. 2

FIG. 3

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FIG. 4 FIG. 5 Fig. 4.-Nephrostogram 6 weeks after Figure 2, showing that the renal pelvis is now intact.

Fig. 5.-Nephrostogram (having substituted smaller nephrostomy tubes) 8 weeks after Figure 2, showing satisfactory healing of the renal pelvis.

pelvis with a covering nephrostomy. This patient was septicremic at the time of re-operation, but the extravasation was successfully treated by nephrostomy and wound drainage.

The second patient became oliguric at 5 days. Renal biopsy showed rejection and he was treated with heavy doses of steroids. Four days later extravasation of urine occurred; at explora- tion a sloughed distal ureter was resected and a new uretero-neocystotomy constructed. Despite a nephrostomy and wound drainage he died of septicamia.

The third patient sloughed his distal ureter. This was resected and urinary drainage estab- lished with a nephrostomy. Further sloughing of the ureter occurred on two occasions but eventually a successful uretero-pelvic anastomosis was performed to the recipient’s own ureter, over an indwelling silastic splint. He then developed a calyco-cutaneous fistula in the lower pole of the kidney. A massive wound abscess developed despite wide wound drainage and the kidney had to be removed eventually because of sepsis and the possibility of secondary hamorrhage.

The fourth patient was managed by anastomosing the donor renal pelvis to the recipient’s ureter, and also performing a nephrostomy, following which he made a straightforward recovery.

5. Culyco-Cutaneous Fistula-These obviously include the 13 nephrostomy cases in the previously mentioned groups, but in addition one following an upper pole infarct secondary to a ligated polar vessel, and one following a lower pole infarct in one of the patients with a sloughed ureter, which was also possibly vascular in origin.

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The first of these last two became septicremic and died despite proximal drainage with a nephrostomy.

B. Ureteric Obstruction.-I . Uretero-Vesical Obstruction.-This occurred in 4 patients, all receiving kidneys from related living donors. One of the patients died.

Three of the 4 presented with urinary infections. All 4 diagnoses were confirmed by I.V.P. The earliest presentation was at 2 weeks post-transplant and the latest at 7 months. Two of the patients became septicaemic with the same organisms as were growing in the urine.

Cystoscopic findings in 3 of these patients showed a pin-hole ureteric orifice at the summit of a “ ureterocoele like ” protrusion into the bladder. One of these was treated by endoscopic meatotomy and the other by re-implantation using the Leadbetter-Politano technique with a satisfactory outcome.

The fourth patient became septicamic 2 weeks after transplantation and developed a pyone- phrosis. The ureter was re-implanted into the bladder, but extravasation followed and 4 months later the donor renal pelvis was anastomosed to the recipient ureter. This patient eventually succumbed to sepsis.

A further patient with uretero-vesical stenosis was discussed above under “ uretero-vesical extravasation ” this being the manner in which she presented.

2. Pelvi-Ureteric Obstruction. Only one instance of this was seen although it has been reported more frequently elsewhere (Salaman et d., 1969). Our patient developed a pelvi-ureteric fistula 7 days post-transplantation. The anastomosis was reconstructed 4 days later with a covering nephrostomy, but he developed a stenosis of the re-anastomosis and died of septicremia following a re-exploration of this.

DISCUSSION

Diagnosis.-The diagnosis of urinary extravasation is not easily made in the transplant patient. Frequently it occurs at a time when the patient is undergoing a rejection episode, and is receiving high doses of steroids. In some of these cases the original oliguria may precede the obvious extravasation by several days. In 4 such patients, the oIiguria was followed by marked pyrexia and rigors, with positive blood cultures, before the extravasation became obvious.

I t is possible that a recipient ureter, left in situ after pre-transplant nephrectomy may have a tenuous blood supply (Martin er al., 1969), and this probably contributes to the high leakage rate of uretero-pelvic anastomosis. If rejection on the donor side is added to ischEmia on the recipient side of the anastomosis then extravasation may follow the high steroid regime used to treat rejection.

The development of high temperatures and positive blood cultures after renal transplantation may be the presenting signs of extravasation and be an urgent indication for drainage of the transplant site and of the urinary tract with a nephrostomy. All the nephrostomies in this series were healed by 7 months after their formation.

Of the 15 cases where nephrostomywas performed for extravasation, 12 kidneyswere salvaged with life-sustaining function. If these leaks are managed in this way we have no evidence to support the contention that the treatment of extravasation is transplant nephrectomy. Two patients in this series did have transplant nephrectomies, but still died of sepsis.

The potentially lethal outcome can be avoided by laying the wound wide open and establish- ing proximal drainage with a nephrostomy. In one of these patients the exposed kidney was covered with split skin grafts from her own thigh, a procedure which was followed by rapid healing of the wound (Fig. 6).

In early extravasation, which is quickly recognised before infection has supervened, i t is a simple procedure to join the donor renal pelvis to the recipient’s ureter when the tissue planes are still definable, but when this is done as a late procedure it poses formidable difficulties in recognis- ing tissue planes and normal landmarks.

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FIG. 6 Extravasation, having been treated by wide exposure of the kidney, and subsequent split skin graft from the recipient’s thigh to the donor kidney surface. The site of

the nephrostomy is closed by a ‘’ butterfly ” adhesive dressing.

Investigations.-When unexplained oliguria and urinary infection occur in the post-trans- plantation period, a high dose I.V.P. is mandatory. It should not be foregone because the patient has a raised B.U.N. as this is frequently due to reabsorption from the extravasated urine in these cases. Cystoscopy and ureteric catheterisation may be required to localise the leakage.

Treatment.-I. IndweIling Ureteric Catheter.-This is seldom successful as the catheter blocks or moves out of position so easily.

2. Wound Drainage.-This is best accomplished by laying the whole wound wide open, exteriorising the kidney. The wound edges can be loosely approximated after a few days, or the kidney can be covered with split skin grafts, when the wound is clean. Failure to establish ade- quate wound drainage usually is followed by uncontrollable sepsis and death. Suction drainage of these wounds is seldom necessary or successful.

3. Nephrostomy.-Adequate wound drainage should be accompanied by proximal drainage of the urinary tract. This may be accomplished by nephrostomy through the upper calyx of the kidney, using a 24 F Malecot catheter via a pyelotomy. This was done on 15 of these patients, and was successful in 12. In these 12 the nephrostomy was performed at the time of diagnosis of extravasation. In the 3 who died it was performed later, after other means of draining the urinary tract had failed with consequent septiczmia.

An irritating complication of treatment by nephrostomy is that the accompanying pyelotomy can be slow to heal. However, provided the wound is adequately drained, this leakage from the renal pelvis slowly ceases as the dose of steroids is reduced.

It is tempting to follow the progress of the urinary fistula by nephrostograms. This seldom adds useful information but is a frequent cause of delay in healing of the pyelotomy if performed too vigorously.

The presence of a nephrostomy need not delay the patient’s discharge from hospital. The tube should be kept in situ until there is evidence on the IVP that the extravasation has ceased. In these patients the nephrostomy was necessary for between 6 weeks and 6 months.

4. Repair of Urinary Fistula.--In 2 patients uretero-vesical leaks in the early post-operative

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period were successfully treated by anastomosing the donor renal pelvis to the recipient's own ureter.

One other patient with a uretero-vesical leak sloughed the distal donor ureter which was reconstructed with a Boari flap. Primary sloughing of the donor ureter was treated by immediate re-implantation in 2 patients, one of whom succumbed. The third transplant with sloughing of the whole donor ureter was eventually successfully anastomosed to his own ureter. The patient lived, but the kidney had to be removed for sepsis following these procedures.

5. Complications of Repair.-The commonest complication of repair of a urinary fistula is delayed healing of the renal pelvis. Whether the donor renal pelvis is opened to permit anas- tomosis to the recipient ureter, or to place a nephrostomy tube, it is very difficult to close the incision in the renal pelvis so that it remains water-tight. It is therefore vital to have an adequately functioning nephrostomy and wound drainage whenever the renal pelvis is opened in the presence of steroids in high dosages.

6. Management of Immune Suppression.-It has been the policy of this unit, when extravasa- tion occurs, to reduce the dose of steroids and Imuran as rapidly as possible and risk the chance of rejection.

SUMMARY

1. Twenty-six renal transplant patients are discussed, in whom there were 27 instances of

2. The diagnostic significance of urinary infection and septiczmia in the presence of oliguria

3. In the presence of urinary extravasation, the value of immediate nephrostomy is stressed

4. Of the 27 patients discussed, 10 died from their urinary tract complications and one other

urinary extravasation and 5 of ureteric obstruction.

is noted, making pyelographic evaluation of the transplant mandatory.

with adequate laying open of the wound to provide drainage.

kidney was lost. REFERENCES

AL-ASKARI, S. (1968). Urological aspects of renal transplantation. In " Human Transplantation,.' ed. Dausset and Rappaport. New York: Grune & Stratton.

MARTIN, D. C., MIMMS, M. M., KAUFMAN, J. J.. and GOODWIN, W. E. (1969). The ureter in renal transplantation. Journal qf Urology, 101, 68CL687.

CARPENTER, C. B., HAGER, E. B., DAMMIN, G . J., and HARRISON, J. H. (1968). Five years experi- ence in renal transplantation with immunosuppressive drugs. Annals ofSwgery, 168,416-435.

PALMER, J. M., KOUNTZ, S. K., SWENSON, R. S., LUCAS, Z. J . , and COHN, R. (1969). Urinary tract morbidity in renal transplantation. Archives of Surgery, 98, 352-356.

PROUT, G . R., HUME, D. M., LEE, H. M., and WILLIAMS, G. M. (1967). Some urological aspects in 93 consecutive renal homotransplants in modified recipients. Journal of Urology, 97, 409425.

SALAMAN, J . R. , CALNE, R. Y., PENA, J . , SELLS, R. A., WHITE, H. J . O., and YOFFA, D. (1969). Surgical aspects of clinical renal transplantation. Brirish Journal ofSurgery, 56, 413417.

WALSH, A. ( 1969). Some practical problems in kidney transplantation. Transp/an/atiotz Proceedings, 1 , 178-183.

MURRAY, J. E., WILSON, R. E., TILNEY, N. L., MERRILL, J. P., COOPER, W. C., BIRTCH, A. G.,

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GENERAL DISCUSSION

Mr. Richard Turner Warwick (London).-The omental pedicle graft technique is a simple procedure and a " renal wrap " probably has a place not only in the management of urinary fistulz following renal transplantation but also in their prevention (Turner-Warwick et al., 1967). The intrinsic vascular and lymphatic defence characteristics of the omentum do not appear to be comprised by immuno-suppression and it seems unlikely that they comprise it.

Quite apart from the treatment of fistulz, an omental wrap provides protection and is a most useful procedure for preventing a kidney from becoming frozenly adherent to the surrounding abdominal wall and major vessels; we have used it in difficult renal stone surgery, not only to add to resolution and healing of infected scar tissue, but also to provide a tissue plane for easy re-entry in the event of recurrent calculi.

The extent of a mobilisation required to provide an omental wrap for a transplanted kidney in the right iliac fossa is, of course, minimal; vertical midline division and detachment from the colon is usually all that is required to provide a small and conveniently located peritoneal exit, leaving an effectively mobile residue for intraperitoneal defence.

REFERENCE

TURNER-WARWICK, R. T., WYNNE, E. J. C., and HANDLEY ASHKEN, M. (1967). The use of ornental pedicle graft in the repair and reconstruction of the urinary tract. British Journal of Surgery, 54, 849-853.