| PRIMARY
RECONSTRUCTION IS A GOOD OPTION IN THE TREATMENT OF URINARY FISTULA AFTER
KIDNEY TRANSPLANTATION
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EDUARDO MAZZUCCHI,
GUILHERME L. SOUZA, MARCELO HISANO, IOANNIS M. ANTONOPOULOS, AFFONSO C.
PIOVESAN, WILLIAM C. NAHAS, ANTONIO M. LUCON, MIGUEL SROUGI
Renal Transplantation
Unit, Division of Urology, General Hospital, University of Sao Paulo Medical
School, SP, Brazil
ABSTRACT
Objectives:
urinary fistula is a morbid complication after renal transplantation leading
to graft losses and patient death. We review and update our data on urinary
fistula after renal transplantation and the outcome after surgical and
conservative management.
Materials and Methods: the charts of 1046
renal transplants were reviewed. Transplants were performed through an
extended inguinotomy; vascular anastomoses to the iliac vessels and urinary
reconstruction accomplished through the Gregoir technique. Fistulae were
diagnosed by urinary leaks through the incision or by the occurrence of
a collection in the iliac fossa. Patient was treated surgically or conservatively
according to the characteristics of the fistula and patient clinical status.
Results: Thirty one fistulae were diagnosed
(2.9%). Twenty nine leaks due to ureteral necrosis and 2 due to reimplantation
fault. The incidence of leaks among cadaver and live donor transplants
was 3.22% and 2.63%, respectively (p = 0.73). Among diabetic and non diabetic
patients the incidence of urinary leaks was 6.4% and 2.6%, respectively
(p = 0.049). Treatment consisted in anastomosis of the graft ureter or
pelvis with the ureter of the recipient in 17 cases with success in 13
(76.5%). Prolonged bladder drainage was employed in 7 cases and the fistula
healed in 4 (57%). Ureteral reimplantation was performed in 3 cases and
did not work in any of them. Ureteral ligature plus nephrostomy was employed
in two cases and worked in one (50%). Percutaneous nephrostomy and ureteral
stenting with double J catheter were employed in one case each and worked
in both.
Conclusions: The anastomosis of the graft
ureter with the ureter of the recipient is a good method for treating
urinary fistulae after renal transplantation when local and systemic conditions
are good. Ureteral ligature associated to nephrostomy should be applied
in cases of unfavorable local conditions or clinically unstable patients.
Key
words: renal transplantation; urinary fistula; treatment outcome
Int Braz J Urol. 2006; 32: 398-404
INTRODUCTION
Since
the beginning of renal transplant era, urological complications have remained
an important source of morbidity and mortality among transplanted patients.
Among urological complications, urinary leaks, ureteral obstruction and
vesico-ureteral reflux are the most frequent ones. Urinary fistula still
leads to graft losses and deaths in the modern transplant era. Its incidence
has fallen in the last decades and is nowadays between 2 and 5% (1-3).
The morbidity and mortality also decreased significantly from the early
80’s due to an improvement in immunosuppression protocols using
low dose steroids, prompt diagnosis and better surgical treatment. Mortality
is now around 8% (4). The number of renal transplant has increased drastically
in our country in the last five years and the real incidence, the main
causes and outcome of patients with this complication after treatment
is unknown. Herein we update our data about urinary fistulae as well the
treatment employed and its results.
MATERIALS
AND METHODS
The
charts of patients transplanted between January 1994 and December 2003
were reviewed. A total of 1046 renal transplants were performed during
the study period; 456 grafts (43.6%) were obtained from live donors and
590 (56.4%) from cadavers. Nephrectomy in live donors was performed either
laparoscopically or by classic lumbotomy. Cadaveric kidneys were procured
by laparotomy and in situ perfusion with Wisconsin or Eurocollins solutions
were employed in all cases.
Renal transplants were performed by the
usual technique; the access to the retroperitoneum was obtained by an
extended inguinotomy. Vascular anastomoses were to the iliac vessels or
exceptionally to the inferior vena cava. Urinary reconstruction was accomplished
by ureteroneocystostomy (Gregoir technique) in the majority of the cases.
A Foley catheter was used to drain the bladder for 5 days after transplant.
Double J stents were used exceptionally when ureteral or bladder condition
was poor. Drains after transplant were used only if bleeding was present
at the end of the surgery.
Immunosuppression was based in a triple
regimen: cyclosporine or rapamycin, azathioprine or micophenolate mofetil
and prednisone. Induction with Okt3 (ortoclone), antithimocyte globulin
(ATG) or anti IL-2 (Daclizumab) were used in re-transplants or in patients
with a high panel reactive antibody. Acute rejection episodes were treated
by corticosteroids or with immunoglobulins.
Urinary leaks were diagnosed by the occurrence
of urine extravasations through the surgical wound, or in the presence
of a fluid collection at the iliac fossa, by the occurrence of intense
dysuria or polaciuria or still, after investigation of unexplained graft
dysfunction. Ultrasound was the initial diagnostic method employed but
the diagnosis was confirmed by cystogram and by fluid analysis when a
collection was present. In some cases a tomography with injection of iodinated
contrast through the Foley catheter was performed.
Surgical treatment was performed in all
patients except those presenting with minimal extravasation at the ureteral
reimplantation site and clinically stable. This group was initially treated
by urinary drainage. In cases of unfavorable outcome after clinical treatment,
surgery was indicated. Surgery was the initial aproach for big extravasation
or when leaks arising from the mid or upper ureter were suspected. We
used the same incision of the transplant to access the fistulae. The type
of surgical reconstruction was based on the intraoperative evaluation
of the extent of the ureteral necrosis and local and systemic condition
of the patient at the time of surgery. Primary reconstruction with the
ureter of the recipient or a new ureteral reimplantation were performed
preferentially when local and systemic condition allowed; if local or
systemic infection were present and the patient was clinically unstable
an ureteral ligature associated to a nephrostomy was performed. Ureteral
stenting alone was used exceptionally. All patients received prophylactic
or therapeutic antibiotic according to the antibiogram of the collected
fluid.
Statistical analysis of the data was performed
using Fischer exact test, with p < 0.05 considered significant.
RESULTS
One
thousand and forty six renal transplants were performed during the study
period; 456 grafts (43.6%) were obtained from live donors and 590 (56.4%)
from cadavers. Mean cold ischemia time was 52 minutes for live donor kidneys
(range 30-105 minutes) and 18 hours for cadaver donor kidneys (range 10-28
hours). Follow-up ranged from 21 to 118 months (mean 67.3 months).Thirty
one urinary leaks were diagnosed (2.9%). Nineteen leaks (61.3%) occurred
among cadaver donor grafts and 12 (38.7%) among live donor grafts. The
incidence of leaks among cadaver transplants was 3.22% and among live
donor transplants was 2.63% (p = 0.73). Fistulae were diagnosed between
the first and the 131 postoperative day (mean 28 post operative day).
Thirteen fistulae (42%) were diagnosed between the first and the 15th
postoperative day and 25 (80%) during the first month after transplant;
patients’ characteristics are in Table-1.
In 4 of the cases (12.9%) an inferior polar
artery was present in the graft and was preserved or reconstructed. One
patient had an ileal bladder augmentation and another one had a continent
reservoir with a Mitrofanoff catheterization mechanism. Ninety three patients
were diabetic at the time of renal transplantation (8.9%); 6 developed
urinary fistulae (6.4%) compared to 25 non diabetic patients (2.6%) (p
= 0.049). Double-J stents were used in 38 transplants; urinary leaks were
observed in 2 of these patients (5.2%). On the other hand urinary leaks
occurred in 29 patients where double J were not used (2.9%) (p = 0.319).
Among 456 grafts from live donors 48 (10.5%)
were obtained by laparoscopy; 2 developed urinary fistula (4.1%); 10 fistulae
were found among 408 open nephrectomy donors (2.4%) (p = 0.36).
Fistulae were caused by ischemic ureteral
necrosis in 29 cases (93.5%) and by reimplantation fault in 2 patients.
Treatment consisted in uretero-ureteric
anastomosis with the ureter of the recipient in 17 cases; in 14 cases
a termino-lateral anastomosis was performed and in 3 patients graft ureter
was anastomosed termino-terminally to the ureter of the recipient. A double-J
catheter was used in all patients. Other forms of treatment comprised
bladder drainage through prolonged catheterization in seven cases, a new
ureteroneocystostomy over a double-J catheter in three cases, percutaneous
nephrostomy in two cases, ureteral ligature plus nephrostomy and ureteral
stenting with double-J catheter in one case each.
Resolution of the fistulae with one procedure
was accomplished in 20 cases (64.5%). Ureteral anastomosis with the ureter
of the recipient was effective as an unique procedure in 13 cases (76.4%),
bladder drainage in 4 (57%), percutaneous nephrostomy in 1 (50%), ureteral
ligature plus nephrostomy and double J stenting in one case each (100%)
and ureteroneocystostomy did not work in any of the 3 cases where they
were employed (Table-2).
Eleven failures occurred and were treated
surgically; treatment options comprised new anastomosis with the ureter
of the recipient (6 cases), ligature of the ureter associated to a nephrostomy
(2 cases), double J stenting (one case), ureter reimplantation (one case)
and nephrectomy. Additionally a nephrectomy of a thrombosed kidney was
performed. Three cases needed a third procedure to heal the fistula. This
way, 64.5% of the urinary fistulae were resolved with one procedure, 90%
with two procedures and 10% needed more than two procedures to heal.
One patient lost his graft due to venous
thrombosis after the surgery for correction of a urinary fistula; 6 other
patients lost their kidneys during follow- up: 5 due to chronic nephropathy
and one due to humoral rejection. At the end of the study period, 17 kidneys
were functioning (55%).
Five patients died during the study period
(16.1%). Two patients died due to infectious complications and sepsis
(6.4%) directly related to the urinary leakage or due to its treatment;
three other patients died of non related causes (one from a laryngeal
tumor, one from pneumonia and one from cerebral ischemia).
DISCUSSION
Thanks
to government policy the number of solid organs transplants experienced
an expressive increase in our country in the last five years. This fact
has also provoked an increase in the number of procurement and transplantation
teams. Urinary fistula is not any more a frequent problem but continues
to occur and may represent a morbid complication. Urinary fistulae arise
frequently due to technical problems, during procurement or transplant
surgery. Ureteral necrosis due to ischemia is the most frequent cause
and can be occasioned during organ retrieval or implantation when extensive
ureteral dissection lead to blood supply damage and consequently to organ
necrosis (2,4-6). Ureteral necrosis was also the most frequent cause of
fistulae in our casuistic, responding to 93.5% of all cases. Several other
risk factors for the development of urinary fistulae have been mentioned:
recipient’s age, number of renal arteries, site of arterial anastomosis,
type of donor, the occurrence of acute rejection episodes, type of urinary
reconstruction, bladder problems, immunosuppressive regimen (4,7-10).
Among them, recipients age < 10 years, use of uretero-ureteric anastomosis
and the use of high dose steroids are considered independent risk factors
(7). In this series, leaks were more frequent among cadaver donor recipients
and significantly more common among diabetic patients at the time of transplantation.
Laparoscopic nephrectomy did not increase significantly the occurrence
of urinary leaks.
Extravesical ureteroneocystostomy has proved
to be easier and with a low incidence of complications (8,11). Routine
ureteral stenting does not reduce significantly the incidence of urinary
fistulae and its use is recommended only in special cases (contracted
bladder, difficult anastomosis) (8,11). In our center the modified Gregoir
technique has been the procedure of choice in the last 35 years and the
incidence of ureteral complications has been low.
Early aggressive management is the key to
prevent graft losses and reduces mortality (3,4). Many options for urinary
fistula management have been described with different rates of success:
ureteral ligature and nephrostomy, ureteroureterostomy, pyeloureterostomy,
ureteroneocystostomy, percutaneous nephrostomy associated to ureteral
stenting, prolonged vesical drainage (4,7-9,11). Percutaneous techniques
like nephrostomy associated to antegrade ureteral stenting works in 40%
of a much selected group of patients presenting with small fistulae from
the distal ureter (8). Prolonged bladder drainage is indicated for small
fistulae arising from the reimplantation site in clinically stable patients
and in our hands a 50% of good results was obtained. Early open surgery
is our preferred approach. Our policy is to perform primary urinary tract
reconstruction whenever local and systemic condition allows. Termino-lateral
anastomosis of the graft ureter or pelvis with the ureter of the recipient
has been our preferred technique for the correction of urinary leaks;
we obtained 77% success with this method, compatible with the results
published in other studies (11,12). Some groups use termino-terminal anastomosis
with the ureter of the recipient (11) with good results but we observed
two cases ureterohydronephrosis of the native kidney after ligation of
the ureter for reconstruction after renal transplantation who required
nephrectomy. Ureteroneocystostomy is used for reimplantation defects or
for small distal ureteral necrosis and in our hands failed in all cases
due to necrosis extension or incomplete ureteral and bladder wall resection
during surgery. Although it did not work in this series, ureteral reimplantation
remains an important option for urinary fistulae management. Ureteral
ligature and nephrostomy is performed when there is gross infection of
the fossa or when the patient presents in sepsis. According to this policy,
a 65% of resolution was obtained with one procedure and 90% with 2 procedures.
Ten patients needed a second procedure due to recurrence of the leakage.
Recurrences were due to insufficient ureter resection, leaving an ischemic
stump extension of the process after the surgery or inadequate anastomosis.
We always leave a double J stent in these cases in order to reduce recurrences
but stents do not work if the necrosis extends. Recurrences were always
managed surgically and an anastomosis with the ureter of the recipient
was the first choice. In one case the local condition was unfavorable
and ureteral ligature with nephrostomy was performed. Some patients needed
a third procedure due to a new recurrence showing that the necrosis can
extend after surgery and that extensive resection of the ureter is frequently
necessary. Additionally we should say that it was not the aim of this
paper to compare all the techniques employed for treating urinary leaks
in this group of patients because this is a retrospective study, not designed
for this kind of comparison; overall, this is an heterogeneous group of
patients.
Mortality directly related to the fistula
or to its correction was high in the early transplantation era (13) and
nowadays is reported to range from 0 to 8% (11); in our series it was
6.4%. These better results are due to an earlier and more aggressive approach,
reduction in the amount of corticosteroids in the immunosuppressive regimen
and to better antibiotics and clinical support. The increase in the experience
with these cases can still improve such results.
CONCLUSIONS
In
this retrospective evaluation urinary fistulae were more common among
cadaver donor and diabetic recipients. The use double J stents did not
reduce significantly the incidence of urinary leaks. Primary anastomosis
of the graft ureter or pelvis to the ureter of the recipient was a good
method for treating urinary fistulae when local and systemic conditions
were good. Ureteral ligature associated to nephrostomy can be used when
local or patient clinical condition is unfavorable.
CONFLICT
OF INTEREST
None declared.
REFERENCES
- Rigg KM, Proud G, Taylor RM: Urological complications following renal
transplantation. A study of 1016 consecutive transplants from a single
centre. Transpl Int. 1994; 7: 120-6.
- Shoskes DA, Hanbury D, Cranston D, Morris PJ: Urological complications
in 1,000 consecutive renal transplant recipients. J Urol. 1995; 153:
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complications of extravesical ureteroneocystostomy in renal transplantation
from living related donors. Urol Int. 2000; 64: 27-30.
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management for the prevention of renal allograft loss and patient mortality
following major urologic complications. Clin Transplantation 1992; 6:
318-322.
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Urol Int. 1992; 49: 76-89.
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of renal transplantation: a series of 1535 patients. BJU Int. 2002;
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parallel incision extravesical ureteroneocystostomy in 1,000 kidney
transplants. J Urol. 1992; 148: 38-40.
- Campbell SC, Streem SB, Zelch M, Hodge E, Novick AC: Percutaneous
management of transplant ureteral fistulas: patient selection and long-term
results. J Urol. 1993; 150: 1115-7.
- El-Mekresh M, Osman Y, Ali-El-Dein B, El-Diasty T, Ghoneim MA: Urological
complications after living-donor renal transplantation. BJU Int. 2001;
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P, et al.: Is routine ureteric stenting needed in kidney transplantation?
A randomized trial. Transplantation. 2000; 70: 597-601.
- Salomon L, Saporta F, Amsellem D, Hozneck A, Colombel M, Patard JJ,
et al.: Results of pyeloureterostomy after ureterovesical anastomosis
complications in renal transplantation. Urology. 1999; 53: 908-12.
- Ghasemian SM, Guleria AS, Khawand NY, Light JA: Diagnosis and management
of the urologic complications of renal transplantation. Clin Transplant.
1996; 10: 218-23.
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Urol Int. 1992; 49: 76-89.
____________________
Accepted after revision:
March 20, 2006
_______________________
Correspondence address:
Dr. Eduardo Mazzucchi
Rua Barata Ribeiro, 490 / 25
São Paulo,SP, 01308-000, Brazil
E-mail: mazuchi@terra.com.br
EDITORIAL COMMENT
The
incidence of urological complications after kidney transplantation varies
from 3% to 14%, with a probable loss of the graft in 10% to 15% of cases
and a mortality rate of up to 15%, despite improvements in prevention,
diagnosis, and treatment as well as the use of new immunosuppressive therapies
(1). Urinary fistulae are considered early complications of transplantation.
They occur in 3-5% of cases in which no double-J stent has been used (2).
Preservation of accessory arteries to the lower portion of the kidney
is important, as they may constitute the blood supply of this segment
of the collecting system or ureter. Their ligation may lead to necrosis
and urinary fistulae (1,2). Urinary fistulae can occur also on bladder
or calyx due to a closure that is not watertight or to necrosis by ligature
of a polar artery respectively (2). Furthermore, European Urology Guidelines
on Renal Transplantation Committee recommends to use a short ureter and
keep the peri-ureteral fat around the hilus and ureteral vessels and to
insert a prophylactic double J-stent and a bladder catheter (2). With
regards to treatment, ureteral fistulae can be treated by open surgery
or by percutaneous approach. In open surgery option, the ureter is re-cut
and a double-J stented, uretero-ureteral anastomosis is made using the
patient’s original ureter. In case of percutaneous treatment, where
it is possible to localize the fistula, it is worth trying nephrostomy
and/or bladder catheter and double-J stent. Bladder fistulae can be treated
by suprapubic or transurethral catheter. Caliceal fistulae are treated
by nephrostomy or bladder catheter and double-J-stent. If this fails,
polar nephrectomy can be tried.
The authors retrospectively report their experience and the data about
urinary fistulas and the outcome after surgical and conservative management.
They report to employ ureteral stent exceptionally at the surgeon discretion
during transplantation. In the authors’ opinion, routine ureteral
stenting does not reduce significantly the incidence of urinary fistulas
and its use is recommended only in special cases.
In
our experience, although the double-J stent appeared to us to be a valid
aid to guarantee the anastomosis patency in the first days immediately
after the transplantation, it did not play a definite role.
Nevertheless,
in a recent review Wilson et al. (3) performed a meta-analysis to examine
the benefits and harms of routine ureteric stenting to prevent urological
complications in kidney transplant recipients. The results of this review
suggest that prophylactic stenting reduces the incidence of major urological
complications and should be recommended on the basis of currently available
randomized controlled trials (3).
REFERENCES
- Li Marzi V, Filocamo MT, Dattolo E, Zanazzi M, Paoletti MC, Marzocco
M, et al.: The treatment of fistulae and ureteral stenosis after kidney
transplantation. Transplant Proc. 2005; 37: 2516-7.
- Kalble T, Lucan M, Nicita G, Sells R, Burgos Revilla FJ, Wiesel M:
European Association of Urology. Guidelines on renal transplantation.
2004. (http://www.uroweb.nl/files/uploaded_files/guidelines/22891_Renal_Transplant.pdf)
- Wilson CH, Bhatti AA, Rix DA, Manas DM: Routine intraoperative stenting
for renal transplant recipients. Transplantation. 2005; 80: 877-82.
__________________
Dr. Vincenzo Li Marzi
Dr. Maria Teresa Filocamo
Dr. Giulio Nicita
Department of Urology II, University of Florence
Florence, Italy
E-mail: vlimarzi@hotmail.com
Dr. Maria
Zanazzi
Department of Nephrology & Transplantation
Careggi Hospital, Florence, Italy
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