Early vs Late Urinary Catheter Removal After Renal Transplantation
Early vs Late Urinary Catheter Removal After Renal Transplantation
The purpose of this study is to compare frequency of UTI, urine leak and need for reoperation
 in patients after renal transplant with early or delayed Foley catheter removal. The
 hypothesis of the ELUCATR trial is that there is no need to keep Foley catheter longer than
 24 hours after kidney transplant due to lack of significant effect on urological
 complications (urine leak, ureter strictures). Early removal can also reduce urinary tract
 infections.

 Main advantage of urinary catheter placement is continual diuresis monitoring and lower
 bladder pressure. Some hypothesize that increased pressure can disrupt ureteroneocystostomy
 with resultant urinary fistula. Clinical practice is to remove the catheter between 1-10
 post-transplant day. Only few studies described removal of Foley catheter in the first 48
 hours. There is no level 1 evidence for timing of urinary catheter removal after kidney
 transplantation.

 Urinary tract infection is a common complication after KTx occurring in about 7-80% patients.
 Studies suggest direct negative effect of UTI on long-term renal allograft function. There
 are several independent risk factors for developing UTI: female sex, diabetes and obesity.
 Duration of catheterization is a modifiable risk factor.

 Urine leak and ureter stenosis are relatively frequent surgical complications of kidney
 transplantation. Urine leaks occur in 2-9% of all kidney transplants. Most of them happen
 within 3 months after surgery. Urinary fistula contributes to mortality and graft loss.
 Majority of them need intervention with nephrostomy, pigtail ureteral stent or surgery.
 Anastomotic or ureter stenosis occurs in 3.1% of all kidney transplants and is usually
 resolved with open ureteroneocystostomy. Diagnosed and treated early, it does not affect
 patient and graft survival. There are no solid data documenting influence of the urinary
 bladder catheterization on fistulas, urinomas, ureter strictures and need for reoperation in
 this set of patients.

 European Best Renal Practice Guidelines recommend removal of the catheter as early as
 possible, however a randomized trial on timing and adverse event rates (urinary tract
 infection, urinary leakage) is needed.
1. Objectives of the study

 1. Main aim of the study:

 Early urinary catheter removal is safe and does not increase urinary complications
 rate. Zero hypothesis is that early and delayed Foley catheter removal have similar
 urinary complications rate (urinary fistula, urinary tract infections). Alternative
 hypothesis is that early catheter removal decreases urinary tract infections.

 2. Primary endpoints:

 -  Urinary fistula or stenosis requiring intervention,

 -  30 day graft function measured as serum creatinine,

 -  1 year graft survival and function.

 3. Secondary endpoints:

 -  Urinary tract infections,

 -  BK virus infection,

 -  length of hospital stay.

 2. Patients and Methods

 2.1 Study organisation

 The study has been designed as a randomized, controlled, open label, multicenter trial to
 compare urinary complications rate between early and delayed Foley catheter removal groups in
 kidney transplant recipients. Computer list of random numbers will be generated, even numbers
 will be assigned to early and odd numbers to late catheter removal, 1:1 randomisation ratio
 is expected. At least 3 large-volume renal transplant centers will participate in the study.
 Randomisation will be supervised centrally by the leader center. Generated numbers will be
 closed in non-transparent envelopes numbered sequentially and shipped to each participating
 center. A center is supposed to use the envelopes for group assignment consecutively with
 increasing numbers. A record of computer-generated number and envelope number will be stored
 at the leader center. An institutional review board of the Medical University of Warsaw
 accepted the study design and patient information leaflet. MS Access-based electronic case
 report file will be used. CRFs will be checked for completeness and concordance with source
 documents and adherence to the study protocol by the study leader.

 2.2 Study design

 Donor and pre-transplant recipient data will be noted in a database. Donor blood, urine and
 preservation solution will be cultured, 10^5 colonies in the former is considered
 significant. Important transplant anatomical features, like multiple renal arteries will be
 noted. After screening and informed consent of the patient for participation in the study,
 kidney transplantation will be performed. Single dose of cefazolin adjusted for patient
 weight will be administered 30 minutes prior to skin incision. Other options of antibiotic
 prophylaxis or preemptive treatment are acceptable, however agent and duration must be noted
 in an electronic Case Report File (CRF). At the beginning of surgical procedure in the
 operating room, sterile catheterization of the urinary bladder and microbiology sampling will
 be performed. After uneventful vascular anastomosis, neoureterocystostomy will be done with
 Lich-Gregoire or a variation of U-stitch technique (McKinnon, other typical). Ureteral stent
 will be placed at surgeon's discretion. Suction drainage will be positioned in graft
 proximity. After wound closure and completion of the surgery, inclusion and exclusion
 criteria will be evaluated. Intraoperative data (blood loss, surgery duration, cold ischemia
 time, details of the anastomosis, utilization of magnifying loupes, pigtail placement) will
 be noted.

 2.3 Eligibility and exclusion criteria.

 2.3.1 Inclusion criteria

 -  Age>18

 -  Kidney transplant recipient

 -  Informed consent signed

 2.3.2 Exclusion criteria BMI<18 or >40 kg/m2 Significant anatomical abnormalities of lower
 urinary tract Previous surgery on bladder or urinary tract Unusual urinary anastomosis
 (Leadbetter-Politano, Boari, conduit, psoas hitch, pyelo-ureteral or uretero-ureteral, double
 ureter) Severe vascular complications during surgery with blood loss >1000 ml Haemodynamic
 shock or profund instability after surgery

 Participants will be randomised to a group early urinary catheter removal (EG) or delayed
 removal group (DG). Early catheter removal will be done 24±6 hours after surgery. In a
 delayed group catheter will be removed 72±6 hours after completion of surgery. Shorter or
 longer catheterization will be considered protocol violation and reasons for ought to be
 explained in source documents and CRF.

 Suction drain will be removed when discharge volume falls below 50 ml/day. If clear discharge
 (>100 ml/day) continues for 2 consecutive days, discharge fluid and serum creatinine ought to
 be measured. If fluid creatinine exceeds its serum concentration by at least 30%, urine
 leakage will be diagnosed and appropriate intervention applied according to surgeon's
 clinical judgement. Only fistulas requiring medical intervention: reintroduction of the
 catheter, endoscopic stenting, nephrostomy or surgery will be considered significant and
 fulfill criteria for primary endpoint of the study.

 The course of study will consist of screen visit, hospitalization (with the transplantation
 procedure, catheter removal, follow up after 48h after catheter removal), follow up visit at
 15 days after procedure and follow up visit at 30 days after procedure (see table 2).
 Patients with urinary complications (fistula, stenosis, infection) will have additional
 visits every 30 days until complete resolution of complication. Patients with stented
 anastomosis who will not have a pigtail removed until day 30 will be followed till 7 days
 after stent removal or resolution of complications would any occur. A final visit 1 year
 after transplantation will assess patient and graft survival, kidney function, late urinary
 complications beyond one month from transplantation.

 2.4 Sample size and statistics

 The investigators assumed early catheter removal reduces the risk of UTI by 10% (RR=0.9) and
 risk of urinary anastomosis complications is comparable. To achieve a power of 80% at p=0,05
 an expected sample size is 450 patients divided fairly into 2 groups. An intent-to-treat
 analysis will be performed. Graft survival analysis and length of hospital stay will be
 calculated with log-rank test. Renal function will be analysed with Student t test, provided
 normal distribution of serum creatinine is observed. Chi2 will be used for analysis of
 urinary complications. Post hoc analysis of donor and recipient entry data will confirm
 groups being comparable fo UTI and urinary fistula risk factors.

 Subgroup analysis in groups with and without urinary stent will be performed.
Inclusion Criteria:

 -  Kidney transplant recipient

 -  Informed consent signed

 Exclusion Criteria:

 -  BMI under 18kg/m2

 -  BMI over 40 kg/m2

 -  Significant anatomical abnormalities of lower urinary tract

 -  Previous surgery on bladder or urinary tract

 -  Unusual urinary anastomosis (Leadbetter-Politano, Boari, conduit, psoas hitch,
 pyelo-ureteral or uretero-ureteral, double ureter)

 -  Severe vascular complications during surgery with blood loss >1000 ml

 -  Underwent haemodynamic shock or profund instability after surgery