Preventing Delayed Graft Function in Kidney Transplant Patients (PDF)

Preventing Delayed Graft Function in Kidney Transplant Patients: A Single-centre, Randomised, Feasibility Trial

The health and quality of life benefits of kidney transplantation are reduced by delayed graft function (DGF). There are a number of modifiable risk factors associated with DGF, such as intraoperative hypotension, the type of intravenous fluid used, glycemic control, and the restriction of blood transfusions. However, these factors have been assessed individually, and their collective effect on reducing the risk of DGF requires further investigation. We first propose a pilot RCT to establish the feasibility of a definitive RCT examining the impact of a treatment bundle of care on DGF.

This will be a single centre, double-blinded pilot RCT including 50 adults undergoing kidney transplantation. Patients will be randomized to either the experimental group, which will consist of a treatment bundle of care, or to the control group, which will consist of routine clinical care for kidney transplant patients. The treatment bundle of care will consist of: the use of plasmalyte for fluid management, maintaining mean arterial pressure > 75 mmHg, identify and treat blood glucose > 9 mmol/L, and a restrictive criteria for red blood cell transfusions (i.e. hemoglobin (Hb) < 70 g/L).

The primary outcome of this pilot study is the recruitment rate. Recruitment rate will be defined as the number of patients who are approached to participate in the study and who are randomized to either the experimental or control group, as a percentage of the total number of eligible kidney transplant patients. The secondary outcomes are: 1) protocol adherence rate and 2) follow-up rate. Protocol success will be defined as a ≥90% compliance with at least 3 of the 4 treatment bundle components. Patient follow-up will end at 90-days after transplant and the target is to follow ≥90% of the patients until this time. DGF and acute rejection will not be assessed in the feasibility trial, and instead this data will be analyzed in the full trial.

Study Overview

• Status: Not yet recruiting
• Conditions: Kidney Injury; Kidney Failure; Kidney Transplant
• Intervention / Treatment: Other: Control Group; Other: Treatment bundle of care

Detailed Description

Background: A number of perioperative factors can impact graft function after kidney transplant, such as hypotension, type of intravenous fluid used, red blood cell transfusions and glycemic control. For example, we recently found that intraoperative hypotension was associated with DGF-CRR following kidney transplant, with a threshold mean arterial blood pressure of 65 mmHg (manuscript submitted). Furthermore, the odds of DGF-CRR increased when the MAP was < 75 mmHg. A method to manage blood pressure during kidney transplant is administering intravenous fluids, either with crystalloids or blood. A recent multicenter, randomized controlled trial showed that plasmalyte, a balanced crystalloid fluid, reduces the incidence of DGF-D after DD- kidney transplant by 25% (i.e. 40% to 30%) compared to normal saline. In the kidney transplant population, blood transfusion was reported to be associated with reduced graft function, early graft loss, and reduced patient survival. As the vast majority of patients receiving blood transfusion receive only 1-2 units, many transfusion events likely could be avoided with better adherence to appropriate triggers, potentially leading to improved outcomes following kidney transplant. Finally, irrespective of a pre-transplant diabetes diagnosis, hyperglycemia (blood sugar > 9.0 mmol/L) in the post-anesthesia care unit is associated with an increased odds of DGF-D following kidney transplant. Therefore, glucose control (i.e. blood sugar < 9 mmol/L) may improve immediate graft function in this patient population.

Rationale: Preserving graft function following kidney transplant is critical to ensuring favourable outcomes. We propose to study the application of a modified version of the KDIGO guidelines for kidney transplant patients. This perioperative bundle of care includes maintenance of MAP >75 mmHg after kidney reperfusion, use of plasmalyte for fluid administration, reducing red blood cell transfusion and identifying and treating a blood sugar > 9 mmol/L. Although this care bundle shows promise for reducing the risk of DGF following transplant, this should first be investigated in a pilot, feasibility trial to ensure successful patient recruitment and adherence to the study protocol, prior to undergoing a full RCT.

Hypothesis: We hypothesize that the proposed perioperative bundle of care will be feasible to implement and improve postoperative outcomes for kidney transplant recipients.

Primary Objectives: The primary objective is to determine the feasibility of recruiting and randomizing kidney transplant recipients to an RCT evaluating the administration of a perioperative bundle of care. Recruitment rate will be defined as the number of patients who are approached to participate in the study and who are randomized to either the treatment or routine clinical care group, as a percentage of the total number of eligible transplant patients. In order to complete a full multicenter trial in a reasonable time period (2-3 years), the number needed to recruit per week is at least 1 patient, but we will aim to recruit 2 patients per week.

The secondary objective is to determine protocol adherence and follow-up rates. The aim is for ≥90% compliance with at least 3 of the 4 components of the perioperative bundle of care i.e. use of Plasmalyte for fluid management, maintenance of MAP > 75 mmHg from time of cross-clamp removal to 4-hours post KT, the initiation of an insulin infusion to maintain a serum blood sugar < 9 mmol/L and avoidance of RBC transfusion unless the Hb < 70 g/L or symptoms of oxygen insufficiency and Hb < 80 g/L. For this trial, patient follow-up will end at 90-days after transplant and the target is to follow ≥90% of the patients until this time. DGF and acute rejection will not be assessed in the feasibility trial, and instead this data will be analyzed in the full trial. Patient follow-up of clinical outcomes will occur at 1-year following KT in the full trial.

Study Significance: This pilot study seeks to assess whether we can recruit kidney transplant patients for an RCT and assess compliance to a surgical care bundle aiming to reduce the incidence of delayed graft function. Preserving graft function after transplant is critical to ensuring favourable outcomes. The primary objectives of this study will assess protocol adherence and outcome collection rates. The results of this pilot trial will serve as the rationale to conduct a large, randomized controlled trial with the use of the surgical care bundle to enhance the recovery of kidney transplant patients.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stuart Dr. McCluskey, MD, PhD, FRCPC; Phone Number: 416-988-6233; Email: Stuart.McCluskey@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • University Health Network
      • Contact: Stuart Dr. McCluskey, PhD, MD, FRCPC; Phone Number: 416-988-6233; Email: stuart.mccluskey@uhn.ca
      • Contact: Wilton Dr. van Klei, MD, PhD
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network
      • Principal Investigator: Stuart Dr. McCluskey, MD, PhD, FRCPC
      • Sub-Investigator: Ryan Dr. McGinn, MD, MSc, FRCPC
      • Sub-Investigator: Wilton Dr. van Klei, MD, PhD
      • Sub-Investigator: Anand Dr. Ghanekar, PhD, MD, FRCSC
      • Sub-Investigator: Matthanja Dr. Bieze, MD, PhD
      • Sub-Investigator: Joseph Dr. Kim, MD, FRCPC
      • Sub-Investigator: Sonia Dr. Rodriguez-Ramirez, MD, FRCPC
      • Sub-Investigator: Yanhong Li
      • Sub-Investigator: Anna Santiago
      • Sub-Investigator: Segum Famure
      • Sub-Investigator: Jo Carrol

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 18 years
• Patients undergoing kidney transplantation
• Living and deceased donor recipients

Exclusion Criteria:

• Multi-organ transplant
• Pre-emptive KT
• Arterial line not planned for surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Group; Routine clinical care for kidney transplant patients	Other: Control Group; Routine clinical care for kidney transplant patients
Experimental: Surgical bundle; The surgical bundle will consist of: the use of plasmalyte for fluid management, maintaining mean arterial pressure > 75 mmHg, identify and treat blood glucose > 9 mmol/L, and a restrictive criteria for red blood cell transfusions (i.e. hemoglobin (Hb) < 70 g/L).	Other: Treatment bundle of care; The treatment bundle of care will consist of: the use of plasmalyte for fluid management, maintaining mean arterial pressure > 75 mmHg, identify and treat blood glucose > 9 mmol/L, and a restrictive criteria for red blood cell transfusions (i.e. hemoglobin (Hb) < 70 g/L).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment rate	Recruitment rate will be defined as the number of patients who are approached to participate in the study and who are randomized to either the treatment or routine clinical care group, as a percentage of the total number of eligible transplant patients. In order to complete a full multicenter trial in a reasonable time period (2-3 years), the number needed to recruit per week is at least 1 patient, but we will aim to recruit 2 patients per week.	Baseline, pre-intervention/procedure/surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Protocol adherence	The aim is for ≥90% compliance with at least 3 of the 4 components of the perioperative bundle of care i.e. use of Plasmalyte for fluid management, maintenance of MAP > 75 mmHg from time of cross-clamp removal to 4-hours post KT, the initiation of an insulin infusion to maintain a serum blood sugar < 9 mmol/L and avoidance of RBC transfusion unless the Hb < 70 g/L or symptoms of oxygen insufficiency and Hb < 80 g/L.	During the intervention/procedure/surgery AND immediately after the intervention/procedure/surgery
Follow-up rate	Patient follow-up will end at 90-days after transplant and the target is to follow ≥90% of the patients until this time. DGF and acute rejection will not be assessed in the feasibility trial, and instead this data will be analyzed in the full trial. Patient follow-up of clinical outcomes will occur at 1-year following KT in the full trial.	90-days after final patient recruited

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Stuart Dr. McCluskey, MD, PhD, FRCPC, University Health Network, Toronto

Publications and helpful links

General Publications

• Sicova M, McGinn R, Emerson S, Perez P, Gonzalez R, Li Y, Famure O, Randall I, Mina DS, Santema M, Wijeysundera DN, Van Klei W, Kim SJ, McCluskey SA. Association of Intraoperative Hypotension With Delayed Graft Function Following Kidney Transplant: A Single Centre Retrospective Cohort Study. Clin Transplant. 2024 Oct;38(10):e70000. doi: 10.1111/ctr.70000.
• Pascoe EM, Chadban SJ, Fahim MA, Hawley CM, Johnson DW, Collins MG; BEST-fluids Investigators and the Australasian Kidney Trials Network. Statistical analysis plan for Better Evidence for Selecting Transplant Fluids (BEST-Fluids): a randomised controlled trial of the effect of intravenous fluid therapy with balanced crystalloid versus saline on the incidence of delayed graft function in deceased donor kidney transplantation. Trials. 2022 Jan 18;23(1):52. doi: 10.1186/s13063-021-05989-w. Erratum In: Trials. 2022 Feb 7;23(1):123. doi: 10.1186/s13063-022-06050-0.

Study record dates

Study Major Dates

• Study Start (Estimated): January 15, 2025
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: November 26, 2024
• First Submitted That Met QC Criteria: December 5, 2024
• First Posted (Estimated): December 9, 2024

Study Record Updates

• Last Update Posted (Estimated): December 9, 2024
• Last Update Submitted That Met QC Criteria: December 5, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Kidney Transplant; Surgical Bundle
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Delayed Graft Function
• Other Study ID Numbers: 24-5286

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Sharing such detailed data can risk exposing sensitive personal information, even if anonymized. Additionally, there are often ethical and legal considerations that restrict the sharing of IPD to protect participants' rights and comply with regulations.

Drug and device information, study documents

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