Preventive Fenestration With and Without Clipping in Kidney Transplantation (PREFEN)

PREventive Effect of FENestration With and Without Clipping on Post-Kidney Transplantation Lymphatic Complications: PREFEN Trial

Post-Kidney Transplantation Lymphatic complications include lymphorrhea and lymphocele, and are some of the most challenging issues after kidney transplantation. The most frequent post-Kidney transplantation complication is accumulation of perirenal fluids, such as urinomas, hematomas, and lymphoceles. Lymphoceles are associated with morbidities such as abdominal discomfort, impaired wound healing, and thrombosis. Lymphoceles may also affect graft function by putting direct pressure on the kidney, or by compressing the ureter or transplant vasculature. The frequency and consequences of post-transplantation lymphoceles make preventive measures highly desirable. Peritoneal fenestration during kidney Transplantation is a simple method for preventing lymphocele formation. Recent studies have evaluated the effectiveness of clipping with metallic clips following fenestration on lymphocele formation and lymph leakage after prostate cancer surgery and laparoscopic retroperitoneal lymph node dissection. However, whether clipping prevents lymphocele formation after kidney transplantation has not been investigated. The aim of the proposed study is to compare the effect of fenestration with and without clipping on incidence of post-kidney transplantation lymphocele and lymphorrhea.

Study Overview

• Status: Unknown
• Conditions: Kidney Transplantation
• Intervention / Treatment: Procedure: Fenestration; Procedure: Fenestration and clipping

Detailed Description

Recent improvements in transplantation techniques, organ matching systems, and modern immunosuppressive regiments have made kidney transplantation a routine operation with acceptable mortality and morbidity rates. Post-kidney transplantation morbidities include vascular and urological complications, and postoperative fluid collections. Perirenal fluid collections, such as urinomas, hematomas, and lymphoceles, are some of most frequent complications following Kidney transplantation, among which post-Kidney transplantation lymphatic collections, are most challenging complications.

The incidence of post-kidney transplantation lymphatic complications is up to 50% and the peak incidence of lymphocele is during the 6th postoperative week (range: 2 weeks to 6 months).

Lymphoceles are usually asymptomatic and identified incidentally by routine ultrasound examination. However lymphoceles may result in morbidities such as abdominal discomfort, impaired wound healing, and thrombosis. Post-kidney transplantation lymphatic complications may also affect graft function by putting pressure on the kidney, or by compressing the ureter or transplant vasculature. The frequency and consequences of post-transplantation lymphoceles make preventive measures highly desirable.

Various preventive methods have been proposed in the literature. Lymphoceles usually originate from unligated lymphatic vessels, therefore precise ligation of donor and recipient lymphatic vessels can reduce lymphocele formation. Compression therapy of the lower limb after kidney transplantation and appropriate immunosuppressive therapy may also reduce lymphocele formation. Some authors have used polymeric sealants/hemostatic biomaterials or povidone-iodine to prevent lymphocele formation. However, the effectiveness and cost-efficiency of these methods has not been conclusively proven. Use of drains in lymphocele prevention has also been previously suggested, but this method remains controversial. Peritoneal fenestration at the time of kidney transplantation is a simple method to prevent lymphocele formation. This method has been widely studied in treatment and prevention of lymphoceles following kidney transplantation. However, to the best of our knowledge, only one randomized controlled trial has been performed to investigate the impact of preventive fenestration in prevention of post kidney transplantation lymphatic complications. This study showed that the prevalence of fluid collections in the fifth postoperative week was significantly higher in the standard group compared to fenestration group. Also, 15.5% of patients in the standard group developed symptomatic lymphoceles requiring treatment during the first postoperative year, versus 3.0% in the fenestration group.

Recent studies have evaluated the effectiveness of extensive clipping using metallic clips following fenestration on lymphocele formation and lymph leakage after prostate cancer surgery and laparoscopic retroperitoneal lymph node dissection. Some surgeons have declared concerns that larger fenestrations increase the risk of hernia. However, risk of closure of the peritoneal fenestration is higher for smaller Windows in the peritoneal cavity. Recently clipping of the edges of peritoneal fenestration was performed in the surgical clinic of the Heidelberg University Hospital to reduce risk of closure of the fenestration after kidney transplantation. However, whether fenestration and clipping prevents lymphocele formation after kidney transplantation has not been investigated.

This clinical Trial is designed to investige the rate of post-kidney transplantation lymphocele and lymphorrhea in two groups of kidney transplantation patients: one with only fenestration and one with fenestration and clipping of the edges. Additionally, graft function and incidence rate of other morbidities will be investigated and analyzed after transplantation.

• Study Type: Interventional
• Enrollment (Anticipated): 78
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • Division of Visceral Transplantation, Department of General, Visceral and Transplantation Surgery, University of Heidelberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18 years
• Provide written informed consent
• Recipients of KTx from deceased donors

Exclusion Criteria:

• Inability to comply with study and/or follow-up procedures
• Recipients of KTx from living donors
• Combined transplantation (e.g. pancreas-kidney transplantation)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: preventive fenestration; Fenestration is performed at the time of kidney transplantation	Procedure: Fenestration; A standardized fenestration of the peritoneum will be performed. A 2 cm incision will be made in the peritoneum that is parallel to the skin incision after the transplant procedure. The peritoneal will not be sutured at the edges to keep the fenestration open. No interpositioning of the omentum will be performed.
Experimental: preventive fenestration and clipping; Fenestration and clipping of the edges are performed at the time of kidney transplantation	Procedure: Fenestration and clipping; A standardized fenestration of the peritoneum will be performed. A 2 cm incision will be made in the peritoneum that is parallel to the skin incision after the transplant procedure. The window edges will be clipped after fenestration using 8 metal clips.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post kidney transplantation lymphocele	Fluid collection of variable size located near to the transplanted kidney in a non-epithelialized cavity. The possibility that the accumulation of fluid is a hematoma, abscess, and urinoma will be ruled out after aspiration of the fluid.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Operation time	From skin incision to skin closure	1 day
Estimated blood loss	Blood loss during operation from skin incision to skin closure (mL)	1 day
Length of hospital stay	From the time of the operation to time of discharge	6 months
Postoperative complications	Postoperative complications will be reported and classified according to the Clavien-Dindo classification.	6 months
Mortality	Death due to any cause.	90 days
Post Kidney transplantation fluid collection	Fluid accumulation near to the transplanted kidney will be diagnosed by ultrasound as routine of the Heidelberg	6 months
Post Kidney transplantation lymphorrhea	Defined as an outflow of more than 50 (milileter) of fluid per day after the 7th post-KTx day. Fluid that flows from the drain, or the site of the removed drain, or surgical wound, which is not blood, pus, or urine will be monitored	6 months
Lymphocele size	Lymphocele diameter and volume will be recorded by ultrasound examination in mL.	6 months
Lymphocele symptomes		6 months
Lymphocele/lymphorrhea severity grade	Severity of lymphocele/lymphorrhea will be graded based on the applied management strategy (Grade A: Observation, Grade B: Non-surgical intervention, Grade C: Surgery).	6 months
Blood Urea Nitrogen Level	Blood Urea Nitrogen Level (mg/dL)	6 months
Plasma uric acid Level	Plasma uric acid Level (mg/dL)	6 months
Serum creatinine level	Serum creatinine level (mg/dL)	6 months
Rate of delayed graft function	Is defined as the need for one or more hemodialysis treatments following transplantation prior to the onset of graft function.	30 days
Glomerular filtration rate	GFR (mL/min/1.73 m2) calculated with "175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female)" Formula	6 months
Rate of primary non-function grafts	number of recipients whose grafts never functions after transplantation	30 days
Retransplantion rate	Rate of retransplantation	6 months

Collaborators and Investigators

• Sponsor: University Hospital Heidelberg
• Investigators: Principal Investigator: Arianeb Mehrabi, MD, Department of General, Visceral and Transplant Surgery, University Hospital

Publications and helpful links

General Publications

• Golriz M, Sabagh M, Mohammadi S, Ghamarnejad O, Khajeh E, Mieth M, Al-Saeedi M, Diener MK, Mihaljevic AL, Morath C, Zeier M, Kulu Y, Mehrabi A. PREventive effect of FENestration with and without clipping on post-kidney transplantation lymphatic complications (PREFEN): study protocol for a randomised controlled trial. BMJ Open. 2020 Oct 13;10(10):e032286. doi: 10.1136/bmjopen-2019-032286.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2018
• Primary Completion (Anticipated): September 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: September 18, 2018
• First Submitted That Met QC Criteria: September 21, 2018
• First Posted (Actual): September 24, 2018

Study Record Updates

• Last Update Posted (Actual): September 24, 2018
• Last Update Submitted That Met QC Criteria: September 21, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: kidney transplantation; Lymphatic complications; preventive fenestration; clipping
• Other Study ID Numbers: S-318/2017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No