Late ureteropelvic necrosis after transplantation

LATE URETEROPELVIC

NECROSIS

AFTER TRANSPLANTATION* LUCA C. RATTAZZI, RICHARD

L. SIMMONS,

PANAYIOTIS JOHN

M.D. t

K. SPANOS,

S. NAJARIAN,

M.D. M.D.f

M.D.

From the Department of Surgery, Minneapolis, Minnesota

University

of Minnesota,

ABSTRACT - Total ureteropelvic necrosis of the transplanted kidney occurred more than one month after transplantation in 5 of 575 consecutive renal transplants performed at the University of Minnesota Hospital since 1963. Necrosis became evident long after normal renal function had been established. Histologic signsofrejection were minimal, but perinephric or periureteral hematomas were found in 3 of 5 patients; post-transplant acute tubular necrosis requiring hemodialysis occurred in all. The pathogenesis of this complication probably involves (1) a primary deficit of blood supplyfiom the renal vessels to the pelvis and ureter, (2) a failure to develop a new ureteral blood supply because of surrounding hematoma, (3) early swelling of the ischemic ureter resulting in oliguria interpreted as acute tubular necrosis, (4) resolution of edema resulting in diuresis, and (5) late patchy ureteral necrosis and _fistulaformation due to ureter-al ischemia.

Kidney transplantation is now an accepted therapeutic modality. Urologic complications unfortunately are common,l+’ but in the majority of instances they can be prevented by improved surgical technique. 9-11One unusual and perhaps unavoidable form of urologic complication has been noted in 5 of 575 transplants performed at the University of Minneapolis Hospitals since 1963. This consists of the appearance of ureteropelvic necrosis more than one month after transplantation, long after normal renal function has been established. Case 1

Case Reports

A thirty-one-year-old white man with insulindependent diabetes received an HL-A identical *Supported by Grant AM 13083 from the United States Public Health Service. tPresent address: Jackson Memorial Hospital, University of Miami, Miami, Florida (Dr. Rattazzi); Division of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota (Dr. Spanos).

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kidney transplant from his sister on May 24,1972. Kidney function which was initially good deteriorated rapidly in the immediate postoperative period requiring hemodialysis for approximately fifteen days. Arteriography, renography, and the clinical course confirmed an initial diagnosis of acute tubular necrosis, and one month after transplantation creatinine clearance had reached a value of 53 ml. per minute. Two months after transplantation the patient noticed minimal scrotal and penile swelling which in the next five days progressed to the point of marked edema of the entire penis and scrotum. Edema was also present in the area of the transplant incision. On admission to the hospital, physical examination revealed swelling of the scrotum and right lower abdominal quadrant. There was no edema of the penis. Moderate tenderness was noted in the right lower abdominal quadrant. The serum creatinine had risen from a value of 1 mg. to 4.5 mg. per 100 ml. Renographic study showed normal extraction but delayed excretion. Kidney dysfunction was thought to be due to acute

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rejection, and antirejection therapy was begun. Swelling involving the right lower quadrant of the abdomen was thought to be due to a seroma, and a small Penrose drain was inserted into the right lower portion of the wound through a small skin incision. In the next twenty-four hours the fluid collection drained approximately 5 L. of strawcolored fluid. The true nature of the collection was marked at first by the excellent response to antirejection treatment. Analysis of the drainage fluid clearly demonstrated this to be urine. Transplant exploration was then performed ten weeks post-transplant revealing necrosis of the entire ureter and distal pelvis to such an extent that restoration of continuity was considered technically unfeasible. Transplant nephrectomy and ureterectomy were carried out. Microscopic examination of the specimen demonstrated minimal signs of rejection and complete loss of cellular detail in the necrotic portions of the collecting system. The patient had an uneventful recovery and later received a second HL-A identical sibling kidney on October 27, 1972. He is well with normal function twenty-four months later. Case 2 In 1969 a thirty-five-year-old white man was found to have deterioration of kidney function due to Goodpasture’s syndrome. On October 11, 1973, he received a cadaveric graft (left kidney presenting double renal arteries of equal size, single vein, and single collecting system with a period of preservation of twenty hours). Arterial anastomosis was made between the first two major branches (superior, inferior gluteal arteries) of the internal iliac artery and the two renal arteries. Postoperatively, because of the inadequate kidney function, the patient required hemodialysis for thirty-one days. Kidney function was stable for the following week (urinary output approximately 2,000 ml. and creatinine clearance 20 ml. per minute). Forty days post-transplant there was a sudden decrease in urinary output. A renogram failed to show deterioration in kidney function, but an infusion intravenous pyelogram demonstrated pyelocaliectasis and ureterectasis. The impression at this time was that partial most likely at the ureteral obstruction, ureterovesical junction, was present. Complete anuria developed in the next twelve hours associated with increasing tenderness over the kidney and generalized ileus. The plane x-ray films of the abdomen demonstrated persistence of

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the dye in the renal pelvis after twenty-four hours. Repeat intravenous and retrograde pyelograms demonstrated urinary extravasation. Exploration of the transplant wound was performed on the forty-second post-transplant day revealing a necrotic ureter and pelvis with a longitudinal defect approximately 1.2 cm. in the most distant portion of the ureter. There was purulent fluid surrounding the extrarenal collecting system. The kidney appeared viable, but the necrotic process had involved the renal pelvis making the reconstruction of the collecting system technically unfeasible. Transplant nephrectomy was carried out. Microscopic examination of specimen demonstrated minimal signs of rejection of the graft and complete necrosis with loss of cellular details involving the renal pelvis and ureter. The postoperative period was uneventful, and the patient is awaiting retransplantation. Case 3

A forty-nine-year-old white man received an HL-A identical sibling kidney transplant on July 10, 1970. Approximately seven days posttransplant serosanguineous fluid started to drain through the operative wounds. The graft rapidly acquired good function; the drainage ceased, and the patient was discharged eighteen days posttransplant. Forty days post-transplant sudden anuria appeared. The patient experienced rapid increase of drainage of clear fluid from the previous drainage site. On admission to the hospital intravenous pyelogram demonstrated extravasation of urine from the collecting system. Retrograde catheterization of the transplanted ureter was unsuccessfully attempted, and exploration of the transplanted kidney was undertaken. At surgery a partially liquefied hematoma surrounded the transplanted kidney, and the ureter itself was found to be necrotic from the ureteropelvic to ureterovesical junction. The pelvis appeared intact. Transplant ureterectomy and pyeloureterostomy using the host ureter were successfully accomplished. The postoperative period was uneventful, and the patient is well four years later. Histologic examination of removed specimens demonstrated no evidence of renal or ureteral rejection. The ureter showed evidence ofa diffuse necrotic process with complete loss of cellular structure. Case 4

A twenty-year-old man received a sibling’s HL-A identical kidney transplant on June 10,

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1970. The post-transplant period was complicated by a short period of “acute tubular necrosis” which required one hemodialysis treatment. The patient was discharged fifteen days posttransplant with excellent renal function. Five weeks after transplant, after twenty-four hours of mild dysuria, oliguria was followed rapidly by anuria associated with pain in the right lower abdominal quadrant and swelling of the transplant area, Renography on admission was consistent with urinary leakage, and needle aspiration of the perirenal space yielded moderate amount of bloody urine. Retrograde catheterization of the ureter was unsuccessfully attempted, and transplant exploration was undertaken. It was found that the pelvis and ureter were surrounded by a small liquefied hematoma, and an area of necrosis involved the pelvis with a 3-mm. defect representing the point of urinary leakage. A 2- or 3-cm. segment of adjacent proximal ureter appeared ischemic and stenotic. Because the necrotic process involved the renal pelvis, a reconstructive procedure was considered technically unfeasible, and transplant nephrectomy was performed. The patient is well three years after retransplantation. Microscopic examination demonstrated the necrotic process involving the pelvis and distal portion of the ureter. A few scattered nests of lymphocytes in the interstitium of the kidney were also identified.

Case 5 A thirty-nine-year-old white man received an HL-A identical sibling kidney transplant on April 12, 1972. The graft presented an inferior polar vessel that was anastomosed end to side to the external iliac artery. Surgery was uncomplicated, but little urinary output was present despite the normal appearance of the graft. Anuria in the immediate postoperative period prompted an arteriogram which demonstrated integrity of the graft vasculature. The patient was maintained on hemodialysis in the following three weeks during which period there was a gradual increase of urinary output and improvement of renal function. Twenty-five days post-transplant a swelling in the transplant wound and decrease in urinary output were noticed. Oliguria rapidly progressed to anuria. Clear signs of acute blood loss with no evidence of the site of hemorrhage were present. Immediate exploration of the transplant wound was undertaken because of the possibility of

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perinephric hemorrhage. At surgery a large hematoma surrounded the kidney and ureter, and free urine was found coming from a necrotic area of the renal pelvis and proximal ureter. Reconstruction of urinary tract continuity was believed to be technically unfeasible, and transplant nephrectomy was performed. The source of the hemorrhage could not be identified. The postoperative course was uneventful, and the patient is well nine months after retransplantation. Histologic examination of the removed graft demonstrated signs of acute tubular necrosis and necrotic changes of the pelvis and proximal third of ureter. There was no evidence of rejection in kidney or ureter. Comment Urinary extravasation following any type of reconstruction of the collecting system and from any of its portions usually presents itself in the first week after grafting. Both Starzl et al. lo and Martin et aZ.12 have observed urinary fistulas more than one month following transplantation. Causes contributing to this late appearance (five to eighteen weeks) of total necrosis of the extrarenal collecting system are difficult to identify. Martin et al. I2have suggested that the ureter may be rejected, however, animal experiments by Robertshaw, Madge, and Kaufhnan,‘3 failed to show a single instance of isolated ureteric rejection. In our patients neither the kidneys nor ureters showed any but the most minimal evidence of rejection, and the ureters appear to have undergone ischemic necrosis. In addition 4 of our patients received HL-A identical sibling grafts which are rarely rejected. Therefore, it appears to be improbable that rejection alone is a significant cause of necrosis of the extrarenal collecting system, although it may contribute to ureteral vascular insufficiency. The most likely cause of late ureteropelvic necrosis is the lack of an adequate blood supply. The extrarenal collecting system is supplied by branches of the renal, spermatic or ovarian, internal iliac, middle hemorroidal, superior and inferior vesicle arteries. Donor nephrectomy requires interruption of this blood supply; the ureteric branches of the renal artery usually remaining undisturbed. In addition, small renal ureteral vessels travel through the peripelvic fat to supply the pelvis and the ureter. Dissection in this area may result in loss of blood supply to the ureter but, even then, spares the pelvis. It has been suggested by Belzer et al. ’that the sacrifice

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TABLE I.

Case Number

Source of Graft

Factors possibly contributing to late ureteropeluic necrosis of transplanted kidneys Perinephric or Post-transplant Periureteral ATN* Hematoma Hemodialysis

Histology

Vascular Abnormality

Diabetes

Antirejection Therapy Plus Routine Posttransplant Treatment

None

Yes

Yes

1

HL-A identical sibling

Minimal signs of rejection

No

Yes

2

Cadaver

Minimal signs of rejection

No

Yes

3

HL-A identical sibling

Yes

Yes

None

NO

No

4

HL-A

Minimal signs of rejection Minimal signs of rejection

Yes

Yes

None

No

NO

5

HL-A identical sibling

Tubular necrosis, no rejection

Yes

Yes

No

No

identical sibling

Double renal artery

Inferior polar artery

NO

twenty-one postoperative

Yes,

days

*Acute tubular necrosis.

of an unrecognized afferent vessel in this region may be responsible for total ureteropelvic necrosis. The double renal arteries or even polar arteries in 2 of our patients should not be considered as the direct cause of this complication (Table I). These abnormalities are relatively frequent, 14and repeated analysis of the results of transplant with double renal arteries by Simmons et al., I5 and Spanos et al. l6 have failed to note increase in ureteral complications after transplantation of kidneys with multiple vessels. Nevertheless, increased difficulty in the dissection of the renal vascular pedicle when double vessels are present, could lead more easily to injury of the ureteropelvie blood supply or to transection of an aberrant vessel. It is likely that the transplanted ureter frequently receives an inadequate blood supply from the renal vessels. The ureter then may represent a “free graft” which can live for a short time on diffusion but must then develop its own vascular supply from the surrounding tissues. The failure to develop its own blood supply because of a surrounding hematoma or interruption ofthe new blood supply by recurrent bleeding within the wound might cause delayed ureteropelvic necrosis (Table I). In this regard 3 of the 5 patients with late ureteropelvic necrosis in this group had hematomas surrounding the transplanted kidney and ureter, and in all 5 patients, including the 4 who received kidneys from HL-A identical siblings, acute tubular necrosis developed in the early post-transplant period (Table I). Acute tubular necrosis is a clinical diagnosis under these circumstances and not a pathologic one, and the renal malfunction may well have been due to edema and obstruction of the ischemic ureter from the time of transplantation. Such edematous

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ischemic ureters may even permit passage of urine for a period of time, but ultimately necrosis results in perforation. The explanation would coincide with the clinical course of sequential acute tubular necrosis, diuresis, and extravasation plus the histologic appearance resembling long-standing ischemic ureteral necrosis. In support of this hypothesis is the previous observation of Weil et al. I1 of 2 patients with urinary extravasation following transperitoneal transplantation of kidneys. In these patients the ureter was “clotheslined” across the peritoneal cavity so that development of new blood vessels to the ureter could not occur. One might expect this complication more frequently in patients with diabetes and in patients who have been treated for a rejection episode with increased levels of steroids or irradiation. Table I demonstrates that only 1 of these patients had diabetes, and only 1 was treated for a possible rejection. Box 185, University of Minnesota Hospitals Minneapolis, Minnesota 55455 (DR. SIMMONS)

References 1. ANDERSON, E. C., et al. :

2. 3.

4.

5.

Urologic morbidity in renal transplantation, South. Med. J. 64: 1513 (1971). BROWN, R. B.: Urological complications of renal homotransplantation, Br. J, Urol. 40: 492 (1968). HAMBURGER J., et al. : Homotransplantation renale humaine. Resultats personnels chez 52 malades. III. Complications extra-renales - Conclusions d’ensemble, Presse Med. 73: 2911 (1965). KELLY, W. D., et al. : Kidney transplantation: experiences at the University of Minnesota Hospitals, Surgery 62: 704 (1967). MCLEAN, L. D., MACKINNON, K. G., INCLIS, F. G.. and DOSSETOR, J. B. : When should renal allografts be removed? Arch. Surg. 99: 269 (1969).

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6. MARTIN, D. C., et al. : Kidney transplants: 92 cases. Results, lessons learned, future prospects, J. Urol. 100: 227 (1968). 7. STRAFFON, R. A., et al. : Four years clinical experience with 138 kidney transplants, ibid. 99: 479 (1968). 8. WOODRUFF, M. F. A., NOLAN, B., ROBSON,J. S., and MACDONALD, M. K.: Renal transplantation in man. Experience in 35 cases, Lancet 1: 6 (1969). 9. BELZER, F. O., et al. : Prevention of urological com-

plications after renal allotransplantation, Arch. Surg. 101: 449 (1970). 10. STARZL, T. E., et al. : Urological complications in 216 human recipients ofrenal transplants, Ann. Surg. 172: 1 (1970). of urological comphca11. WEIL, R., et al. : Prevention tions after kidney transplantation, ibid. 174: 154 (1971).

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12. MARTIN, D. C. MIMS, M. M., KAUFMAN, J. J., and

GOODWIN,W. E. : The ureter in renal transplantation, J. Urol. 101: 680 (1969). 13. ROBERTSHAW,G. E., MADGE, G. E., and KAUFFMAN, H. M., JR. : Ureteral pathology in treated and untreated renal homografts, Surg. Forum 17: 236 (1966). 14. ROSS, J. A., SAMUEL, E., and MILLAR, D. R.: Variations in the renal vascular pedicle, Br. J. Urol. 33: 478 (1961). 15. SIMMONS,R. L., TALLENT, M. B., KJELLSTRAND,C.

M., and NAJARIAN,J. S. : Kidney transplantation from living donors with bilateral double renal arteries, Surgery 69: 201 (1971). 16. SPANOS, P. K., et al. : Kidney transplantation from living related donors with multiple vessels: revisited, Am. J. Surg. 125: 554 (1973).

a problem

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