Vol. 114, September Printed in U.S.A.

THE JOURNAL OF UROLOGY

Copyright© 1975 by The Williams & Wilkins Co.

CINE-FLUOROSCOPIC STUDIES OF URETERAL FUNCTION IN THE HUMAN RENAL TRANSPLANT AKIRA HASEGAWA, M. J. V. SMITH* HYUNG M. LEE

AND

DAVID M. HUMEt

From the Department of Surgery, Medical Collepe of Virginia, Richmond, Virginia

ABSTRACT

During a 14-month period 73 satisfactory fluoroscopic studies were done on 59 kidney transplant Ureteral peristalsis was seen in 90 per cent of these studies and there was no difference between patients receiving living related donor kidneys and those receiving cadaveric kidneys. When ureteral activity was studied during rejection episodes only 54 per cent of the studies showed activity. An effort was made to relate aperistaltic ureteral activity to renal function, warm ischemia time, urinary tract infection, number of rejection episodes and tissue matching but no positive correlation could be made except the concurrent clinical diagnosis of rejection. The behavior and function of the ureter in a transplant patient have long been neglected, although rejection of the ureter does occur. 1 Most investigators of transplant cases have directed their attention to the kidney and the changes that occur as a result of the introduction of an allograft into the host. Many changes in the kidney and ureter are occurring simultaneously but the lack of good methods to study ureteral changes may be a reason for their apparent neglect. This fact is somewhat surprising because of the known significant ureteral complications with the loss of a transplanted kidney or even the mortality associated with this problem. Some known factors that seem to influence the function of the ureter in a transplant patient include the tenuous arterial supply and the possibility of mechanical damage to this organ during its procurement and subsequent perfusion. Because of these factors some investigators use the pyeloureteral anastomosis, which seems to have as many problems as other methods. Although we have had no experience with this method Sanford and associates have noted abnormal ureteral peristalsis following its use. 2 It is also known from clinical experience and from the work of Teague and Boyarsky that infection, particularly by Escherichia coli and Aerobacter, will cause inhibition of ureteral peristalsis. 3 This effect is not generated by systemic infection but requires the presence of the bacteria and Accepted for publication November 22, 1974. Read at annual meeting of Mid-Atlantic Section, American Urological Association, Hot Springs, Virginia, October 24-26, 1974. Supported by National Institutes of Health Transplant Grants 9642 and 9947. * Requests for reprints: Medical College of Virginia, Box 176, Richmond, Virginia 23298. t Deceased. 381

possibly their endotoxins to be in the ureteral lumen. Boyarsky and associates have shown that ureteral innervation is essential for proper activity. 4 O'Conor' and others• have not been able to demonstrate any need for ureteral innervation for functional peristalsis to take place. However, Sanford and associates have shown that peristalsis was present in 14 of 18 patients receiving living related transplants, while it was found in only 4 of 10 cadaveric transplants. 2 The only factor that they could correlate with abnormal ureteral activity was warm ischemia time. Preliminary work in our laboratories has revealed the possibility that rejection phenomena may have a part in ureteral dysfunction. 7 • 8 We also have noted that a blood supply will develop in the lower third of the implanted ureter at approximately 1 month after isolated transplantation. Because of the apparent paucity of knowledge in this field all patients who have undergone renal transplantation have been investigated by means of cine-fluoroscopy during infusion urography. MATERIALS AND METHODS

Our study involves all kidney transplant recipients who were seen between November 1972 and February 1974. Infusion urograms were obtained using 300 ml. meglumine diatrizoate (reno-M dip 30 per cent) intravenously during a 15-minute period. Immediately upon completion of the infusion study cine-fluoroscopic studies were completed and abdominal and oblique films were obtained. In addition a "squat shot" as described Boyce and associates was obtained. 9 Continuous fluoroscopic monitoring was done and 16 mm. cine-spot films were obtained on a Picker x-ray cine-fluorographic unit equipped with an image intensifier to ureteral and the

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coordinate movements of the recipient bladder and trigonal musculature. Urinalysis, urine culture, complete blood count, blood urea nitrogen, serum creatinine and electrolyte values, and creatinine and urea clearances were all performed on the day of these studies.

the transplant and only 7 showed no peristaltic activity of ureter (11.6 per cent). There was a statistically significant difference between these 2 groups (table 2). Ten of the 73 studies were done when the patients had significant urinary tract infection. The site of infection was not exactly documented. Organisms causing urinary tract infection were Pseudomonas in 4, yeast in 2, Proteus vulgaris, E. coli, Staphylococcus and Streptococcus in each of the remainder. As table 3 shows, 3 of 10 studies (30 per cent) done during urinary tract infection showed no ureteral peristaltic activity, compared to 10 of 63 studies (16.2 per cent) without urinary tract infection which did not show any ureteral activities. These differences are not statistically significant. There were 2 studies done when the patient was thought to have urinary tract infection and clinical rejection crisis-1 showed good ureteral function and the other did not show any ureteral peristalsis. An analysis of the relationship of renal function and peristaltic activity is presented in table 4. There was no observable correlation among serum creatinine, creatinine clearance and peristaltic activity. In 20 patients with living related donors, we were unable to find any correlation with the match (table 5). This was also true in a group of 53 studies in which presensitization data were available. Table 6 shows numbers of previous clinical rejection episodes of each group. The patients who did not show any ureteral activity had an average

RESULTS

There were 73 studies available for analysis in which all of the aforementioned criteria had been satisfied. The studies were done on 59 kidney transplant recipients, 12 patients having 2 separate studies and 1 having 3. There were 28 living related kidney transplants and 31 cadaver kidney transplants. The interval between the transplantation and this study ranged from 6 days to 8 years 6 months. Our findings are summarized in table 1, in which the presence or absence of peristaltic activity is recorded. There were 13 instances in which no ureteral peristalsis could be observed during study, even though the ureter was seen. Table 2 shows the timing of the study as related to the clinical rejection episodes. The studies carried out between the day of starting anti-rejection therapy and 2 days after stopping anti-rejection therapy were considered as during rejection crisis. During clinical rejection 13 cine-fluoroscopic excretory urograms (IVPs) were performed. In 7 studies ureteral peristalsis was present, while in 6 no ureteral peristaltic activity was seen (46.9 per cent). In 60 studies that were done "not during clinical rejection" 53 showed ureteral peristalsis of TABLE

1. Peristaltic activity of ureter Peristalsis No.(%)

Living related donor kidney transplant 29 (88) 25 (89) Cadaver donor kidney transplant 31 (77) 28 (90) Total studies 60 (82) 53 (90)

No. IVP studies* No. pts. No. IVP studiest No. pts. No. IVP studies* No. pts.

No Peristalsis No.(%)

Totals No.(%)

4 (12) 3 (11)

33 (100) 28 (100)

9 (23) 3 (10)

40 (100) 31 (100)

13 (18) 6 (10)

73 (100) 59 (100)

• 5 patients had 2 separate studies. t 7 patients had 2 separate studies; 1 patient had 3 separate studies. * 12 patients had 2 separate studies; 1 patient had 3 separate studies. TABLE

2. Ureteral peristaltic activity during clinical rejection episode

During rejection Not during rejection

Studies

Peristalsis No.(%)

No Peristalsis No.(%)

13 60

7 (54)* 53 (88)*

6 (46) 7 (12)

• Statistically significant (a = 0.05). TABLE

With infection Without infection • Not significantly different.

3. Ureteral peristaltic activity during urinary tract infection Studies

Peristalsis No.(%)

No Peristalsis No.(%)

10 63

7 (70)* 53 (84)*

3 (30) 10 (16)

383

CINE-FLUOROSCOPIC STUDIES OF URETERAL FUNCTION IN TRANSPLANTS TABLE

4. Kidney function and ureteral peristaltic activity in transplant No.(%)

Less than 1.5 mg./dl. 1.6 to 3.0 mg./dl. More than 3.1 mg./dl. Totals

45 (100)

21 (100) 7 (100) 73 (100)

Peristalsis No.(%)

No Peristalsis No.(%)

39 (87)* 17 (81)* 4 (57)*

6 (13)

60 (82)

13 (18)

4 (19) 3 (43)

* Not significantly different. TABLE

Terasaki Match

5

Peristalsis

No Peristalsis

Totals

H.L.A. matching and ureteral peristaltic activity in living related donor transplant Grade A GradeB GradeC GradeD GradeE

10* 10 { O'' 8

{ O*1* 7*

Peristalsis No.(%)

At Transplant

jO

0 I0 2

{1

1 0

No Peristalsis No.(%)

Presensitization and ureteral peristaltic activity in human kidney transplant Per cent reactive antibody less than 5 29 (78) 8 (22) Per cent reactive antibody more than 5 14 (87) 2 (13)

Totals No.(%) 37 (100) 16(100)

* Not significantly different. TABLE

6. Previous rejection episodes and ureteral peristaltic activity Studies

Av. No. Previous Rejection Episodes

60 13 73

0.85 (0-3)* 1.38 (0-3)* 0.94 (0-3)

Visible peristalsis No peristalsis Totals

42 hours total ischemic time (range 14 hours 50 minutes to 49 hours). No correlation could be detected between the length of warm ischemia and ureteral function, nor does total ischemic time show any influence on ureteral function. DISCUSSION

'' Not significantly different.

of 1.38 previous clinical rejection episodes. On the other hand, the patients who showed visible ureteral activity had 0.85 previous clinical rejection episodes. These values are statistically insignificant. Of 25 cadaveric kidneys, for which record of warm ischemic time, cold perfused ischemic time and total ischemic time were available, 28 studies were performed. Five kidneys had more than 10 minutes of warm ischemic time and all of them showed visible ureteral peristalsis. This result does not agree with findings of others 2 when the cadaveric kidney with more than 10 minutes of warm ischemic time did not show any peristaltic activity. Of the 6 kidneys that did not show ureteral activity 4 kidneys had no warm ischemic time and the other 2 had 3 and 6 minutes of warm ischemic time, respectively. The average warm ischemic time in which the ureter did not show any activity was 1 minute 30 seconds (0 to 6 minutes). Average warm ischemic time in which the ureter had peristaltic activity was 4 minutes 14 seconds (0 to 20 minutes). The 6 cases in which peristalsis of the ureter could not be seen had total ischemic time 14:30, 30:00, 43:52, 31:04, 17:11 and 15:39 (average 25 hours 22 minutes). On the other hand, average total ischemic time of the 22 kidneys which showed ureteral peristalsis was 28 hours 8 minutes, indud4 instances in which the had more than

It is evident from these studies that we have been unable to confirm the findings of Sanford and associates in regard to the influence of warm ischemic time on the incidence of aperistaltic ureters.2 It would seem from our own experience that some of their findings might reflect the vascular damage to the ureteral blood supply. Certainly 2 of our aperistaltic ureters came from donors with multiple arteries and it may be that this defect is secondary to true vascular insufficiency, as suggested by Hricko and associates. 10 It is evident that our findings in regard to the association of or the development of aperistaltic ureters during clinical rejection episodes confirm the report of Belitsky and associates, 11 although they found only 25 per cent of ureters of kidneys undergoing rejection episodes which showed peristalsis while we report 54 per cent. On analysis of the numbers involved there is no statistical significant difference between the 2 reports. It should be stressed again that we report peristaltic activity rather than trying to quantitate its frequency, efficiency or initial location. Even after the study was completed we were unable to identify any quantitative or qualitative data on the dynamics of ureteral activity by reviewing all our cine studies. However, on no occasion was retrograde or churning movement of ureteral peristalsis seen. Studies on the isolated ureter of the shown that lS

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complete loss of the muscle tissue with hyalinization. These studies may well account for the pipe stem ureters that have no activity but seem to act as a tube through which urine flows by gravity. The question raised by this finding is what effects does this static form of urinary transport have upon kidney function. Currently, our investigative methodology would seem to be too crude to give meaningful answers. On the basis of a limited clinical experience it would seem that if a transplanted ureter shows no activity even after extensive immunosuppression any attempt to use that ureter for recenstructive work (following a small leak for example) is doomed to technical failure. The most logical explanation for our findings in the ureter would suggest that it is influenced to a considerable degree by the clinical course of the patient. In the initial period there would appear to be 2 local factors at work. First, the vascular supply is most vulnerable at this time and any mishandling can result in microinfarcts. If these infarcts are extensive they may well result in some small localized strictures, not infrequently seen. This aspect of ureteral function would appear to be of less importance after a period of 2 months as there appears to be neovascularization of the lower ureter. 7 The reports of Belitsky and associates of ln-?eased peristaltic activity in transplanted ureters during the early post-transplant period which subsequently recovers may well be based on this component. 11 The second component, rejection, acts throughout the life of the graft and whether peristalsis returns or not would seem to be dependent upon the extent of muscle damage that takes place. So one can see the full spectrum from no appreciable damage to a total aperistaltic ureter which acts as a rigid tube.

Mrs. Griff and Miss L. A. Cottrell provided technical assistance. REFERENCES

1. Robertshaw, G. E., Madge, G. E. and Kauffman, H. M., Jr.: Ureteral pathology in treated and untreated renal homografts. Surg. Forum, 17: 236, 1966. 2. Sanford, E. J., Glenn, J. F. and Anderson, E. E.: Ureteral function in renal transplantation. J. Urol., 108: 521, 1972. 3. Teague, N. and Boyarsky, S.: Further effects of coliform bacteria on ureteral peristalsis. J. Urol., 99: 720, 1968. 4. Boyarsky, S., Labay, P., Kirshner, N. and Gerber, C.: Does the ureter have nervous control? J. Urol., 97: 627, 1967. 5. O'Conor, V. J., Jr.: The role of the ureter in renal transplantation. -II. A full length ureteral transplantation. J. Urol., 86: 51, 1961. 6. Murray, J. E., Merrill, J. P. and Harrison, J. H.: Kidney transplantation between seven pairs of identical twins. Ann. Surg., 148: 343, 1958. 7. Texter, J. H., Jr.: The isolated ureter. A model for stvdy of ur8teral rejection. Urology, 2: 244, 1973. 8. Texter, J. H., Jr., Bokinsky, G. and Broecker, B.: Ureteral rejection in isolated allograft ureter. Urology, 4: 37, 1974. 9. Boyce, W. H., Harris, J. A. and Vest, S. A.: The dorsal cystogram or "squat shot": a technique for roentgenography of posterior bladder and pelvic ureters. J. Urol., 70: 969, 1953. 10. Hricko, G. M., Birtch, A. G., Bennett, A. H. and Wilson, R. E.: Factors responsible for urinary fistula in the renal transplant recipient. Ann. Surg., 178: 609, 1973. 11. Belitsky, P., Klauber, G. T., Toth, J., Morehouse, D. D. and MacKinnon, K. J.: Ureteral dynamics in human renal transplantation. A cineradiographic study. J.A.M.A., 220: 1087, 1972.

Cine-fluoroscopic studies of ureteral function in the human renal transplant.

During a 14-month period 73 satisfactory fluoroscopic studies were done on 59 kidney transplant recipients. Ureteral peristalsis was seen in 90 per ce...
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