Preventing Delayed Graft Function in Kidney Transplant Patients: A Single-centre, Randomised, Feasibility Trial
Phase: NA
Conditions: Kidney Transplant, Kidney Failure, Kidney Injury
Sponsor: University Health Network, Toronto

                                                                                                                                                                          
Dept. of Anesthesiology and Pain Medicine   TGH                                                         
PDF Trial 
 
 
Study protocol – Version 1.0 
March 27, 2024 
 
Page 1 of 15 
 
  
 
 
Study Protocol PDF Trial  
 
 
Study working title: 
The PDF Trial: Preventing Delayed Graft Function in Kidney Transplant Patients: A 
single-centre, randomised, feasibility trial  
Version 1.0 / March 27, 2024 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Principle Investigator 
PI 
 
Stuart A McCluskey 
Email  
stuart.mccluskey@uhn.ca 
Phone  
14-8561 Mobile 416 988 6233 
Location 
TGH, Eaton Building, 200 Elizabeth St, 3rd Floor, Room 3EN-405, 
Toronto, Ontario, Canada, M5G 2C4 
 
 
 
 
 
 
 
 
 

                                                                                                                                                                          
Dept. of Anesthesiology and Pain Medicine   TGH                                                         
PDF Trial 
 
 
Study protocol – Version 1.0 
March 27, 2024 
 
Page 2 of 15 
 
 
 
 
 
 
 
Protocol authors 
Marc Sicova, Anesthesiology  
Ryan McGinn, Anesthesiology 
Wilton van Klei, Anesthesiology 
Joseph Kim, Nephrology 
Stuart A. McCluskey, Anesthesiology 
Principal investigator Stuart A. McCluskey, MD, PhD, FRCPC 
Co-investigators 
Ryan McGinn, MD MSc FRCPC 
Wilton van Klei, MD,  
Anand Ghanekar, PhD, MD, FRCSC 
Matthanja Bieze, MD PhD 
Joseph Kim, MD FRCPC 
Sonia Rodriguez-Ramirez, MD FRCPC 
Yanhong Li, Statistician 
Anna Santiago, Statistician 
Segun Famure, Research Manager 
Jo Carroll, Study Coordinator 
Document type 
Study protocol  
Document status 
Version 1.0 
Date 
March 27, 2024  

                                                                                                                                                                          
Dept. of Anesthesiology and Pain Medicine   TGH                                                         
PDF Trial 
 
 
Study protocol – Version 1.0 
March 27, 2024 
 
Page 3 of 15 
 
1. PROTOCOL SYNOPSIS 
TITLE 
The PDF Trial: Preventing Delayed Graft Function in Kidney 
Transplant Patients: A single-centre, randomised, feasibility trial 
OBJECTIVES 
Primary Objectives 
To determine the feasibility of recruiting and randomizing kidney 
transplant recipients to an RCT evaluating the administration of a 
perioperative bundle of care. The bundle of care is based on the 
best available evidence and includes the use of plasmalyte for fluid 
management, maintaining mean arterial pressure > 75 mmHg, 
identify and treat blood glucose > 9 mmol/L, and a restrictive RBC 
transfusion trigger (i.e. hemoglobin (Hb) < 70 g/L).  
Secondary Objectives 
To determine protocol adherence and follow-up rates.   
DESIGN / PHASE Randomized controlled feasibility trial.   
STUDY 
DURATION 
September 1, 2024 – October 1, 2025 
CENTRE 
Toronto General Hospital, Department of Anesthesia and Pain 
Management and Department of Nephrology, Ajmera Transplant 
Centre, Toronto General Hospital, University Health Network, 
Toronto, ON, Canada 
PATIENTS / 
GROUPS 
• Patients undergoing a kidney transplantation 
INCLUSION 
CRITERIA 
• ≥ 18 years of age undergoing kidney transplantation 
surgery 
• Recipients of living or deceased kidney donors 
Note: If a patient has one or more kidney transplant surgeries 
in the study period, each transplant surgery will be considered 
separately. 
EXCLUSION 
CRITERIA 
• Multi-organ transplant  
• Pre-emptive kidney transplantation (transplant prior to 
initiation of dialysis) 
• Functional arterial line not available  
STUDY PERIODS TBD  
ENDPOINTS 
Primary endpoints – Feasibility Outcomes 
• Recruitment rate 
 
Secondary endpoints – 3 months following kidney transplant  
• >90% success in implementing the full bundle of care and 
each item individually within the bundle 
• Follow-up rate 

                                                                                                                                                                          
Dept. of Anesthesiology and Pain Medicine   TGH                                                         
PDF Trial 
 
 
Study protocol – Version 1.0 
March 27, 2024 
 
Page 4 of 15 
 
Covariates: 
• Demographic factors (age, sex, height, weight) 
• Elixhauser comorbidities  
• Pre-operative hemoglobin and other laboratory values 
(INR, hematocrit, platelet, albumin, serum creatinine) 
• Pre-operative erythroid stimulating agents during the 30 
days prior to kidney transplantation  
• Pre-operative iron supplementation (iv and oral) 
• Living or deceased donor kidney 
STATISTICAL 
METHODOLOGY  
Categorical variables will be summarized as frequencies and 
percentages; continuous variables as means with standard 
deviation. The unadjusted association of potential predictors of the 
secondary outcomes will be evaluated for both continuous (t test, 
Wilcoxon rank sum test) and categorical (χ2 test, Fisher’s exact 
test, Mantel-Haenszel χ2 test) variables. Independent predictors of 
the secondary outcomes will be identified by multivariable logistic 
regression analysis.  
 
 
 

                                                                                                                                                                          
Dept. of Anesthesiology and Pain Medicine   TGH                                                         
PDF Trial 
 
 
Study protocol – Version 1.0 
March 27, 2024 
 
Page 5 of 15 
 
2. LIST OF ABBREVATIONS 
 
CBC  
 
 
Complete blood count 
DD-KT 
 
 
Deceased donor kidney transplant recipient 
DGF 
 
 
Delayed graft function 
DGF-CRR 
 
 
DGF based on serum creatinine reduction ratio 
DGF-D 
DGF based on the need for dialysis within the first week of 
transplantation 
ESA  
 
 
Erythroid stimulating agents 
INR 
 
 
 
International normalized ratio 
 
 
 
 
IV 
 
 
 
Intra-venous 
Kidney Donor  
Prediction Index   
 
KDPI  
LD-KT  
 
 
Living donor kidney transplant recipient 
RBC  
 
 
Red blood cell 
TGH  
 
 
Toronto General Hospital 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                                                                          
Dept. of Anesthesiology and Pain Medicine   TGH                                                         
PDF Trial 
 
 
Study protocol – Version 1.0 
March 27, 2024 
 
Page 6 of 15 
 
 
3. TABLE OF CONTENTS 
 
1. PROTOCOL SYNOPSIS 
3 
2. LIST OF ABBREVATIONS 
5 
3. TABLE OF CONTENTS 
6 
4. BACKGROUND INFORMATION 
8 
4.1 BACKGROUND/INTRODUCTION 
8 
4.2 STUDY RATIONALE 
9 
5. STUDY OBJECTIVES (HYPOTHESIS) 
9 
5.1 PRIMARY OBJECTIVE 
9 
5.2 SECONDARY OBJECTIVES 
9 
6. STUDY DESIGN 
9 
6.1 STUDY TYPE 
9 
6.2 STUDY POPULATION 
9 
6.2.1 DEPARTMENT 
9 
6.2.2 SUBJECT 
9 
6.2.3 INCLUSION CRITERIA 
9 
6.2.4 EXCLUSION CRITERIA 
10 
6.2.5 STUDY DURATION 
10 
6.3 OUTCOMES 
10 
6.3.1 PRIMARY OUTCOMES 
10 
6.3.2 SECONDARY OUTCOMES 
ERROR! BOOKMARK NOT DEFINED. 
6.3.3 COVARIATES 
10 
7. METHODOLOGY 
11 
7.1 SCREENING AND INCLUSION 
11 
7.2 SAMPLE SIZE CONSIDERATIONS 
11 

                                                                                                                                                                          
Dept. of Anesthesiology and Pain Medicine   TGH                                                         
PDF Trial 
 
 
Study protocol – Version 1.0 
March 27, 2024 
 
Page 7 of 15 
 
7.3 DATA SOURCES 
11 
7.4 STUDY INTERVENTION  
11 
7.5 STATISTICAL METHODS AND ENDPOINTS ANALYSIS 
11 
7.6 STATISTICAL SOFTWARE 
11 
7.7 DATA MANAGEMENT 
12 
8. ETHICAL AND LEGAL ASPECTS 
12 
8.1 INFORMED CONSENT 
12 
8.2 CONFIDENTIALITY 
12 
8.3 ETHICS AND GOOD SCIENTIFIC PRACTICE 
12 
8.4 BENEFIT AND RISK ASSESSMENT 
12 
9. FINANCIAL ASPECTS 
13 
10. REFERENCES 
14 
 
 
 

                                                                                                                                                                          
Dept. of Anesthesiology and Pain Medicine   TGH                                                         
PDF Trial 
 
 
Study protocol – Version 1.0 
March 27, 2024 
 
Page 8 of 15 
 
4. BACKGROUND INFORMATION 
4.1 Background/Introduction  
Kidney transplantation (KT) is the treatment of choice for patients with end-stage 
kidney disease, improving survival, and quality of life.1 Unfortunately, delayed graft 
function (DGF) occurs in 20-30% of deceased donor kidney transplant (DD-KT) 
recipients  and often requires dialysis.2-5 DGF-D refers to the requirement for at least 
one session of dialysis within the first week after transplantation, and is associated with 
worse graft and patient survival making efforts to avoid this complication important.6,7 
Dialysis is required much less often after living donor kidney transplantation (LD-KT) 
(1-3%).8 In order to assess graft function after LD-KT, a delay in kidney graft function 
is better identified by a suboptimal (i.e., < 30%) reduction in serum creatinine between 
postoperative days 1 and 2 (DGF-CRR).8-12 DGF after LD-KT is also associated with 
long-term complications.13 
 
Optimizing perioperative care to support graft kidney function in order to decrease the 
incidence of DGF may improve outcomes, reduce hospital length of stay and mitigate 
morbidity.14-16 In other surgery, postoperative acute kidney injury (AKI) has many 
similarities to DGF and measures to prevent AKI may be used to guide perioperative 
care in KT. For example, in cardiac surgery The Kidney Disease: Improving Global 
Outcomes (KDIGO) guidelines have been shown to reduce the incidence and severity 
of AKI.17 A single centre, randomized controlled trial determined that the use of the 
KDIGO guidelines resulted in a 16% absolute risk reduction of AKI following cardiac 
surgery, compared to routine perioperative care.18 In addition, several Enhanced 
Recovery After Surgery (ERAS) protocols developed for the non-cardiac surgery 
population have been proposed for KT. Similar to the KDIGO Guidelines, avoiding 
nephrotoxins, maintaining normothermia and euglycemia, and early ambulation are 
proposed.19-21  
 
Still, these suggestions do not consider the most recent evidence and do not include 
other perioperative factors that impact graft function after KT, such as hypotension,22 
type of intravenous fluid used,23 red blood cell transfusions24-28 and glycemic control29. 
For example, we recently found that intraoperative hypotension was associated with 
DGF-CRR following KT, 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 KT 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-KT by 25% (i.e. 40% to 30%) compared to normal 
saline.30 In the KT population, blood transfusion was reported to be associated with 
reduced graft function, early graft loss, and reduced patient survival.24-28 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 KT. 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 KT. Therefore, 
glucose control (i.e. blood sugar < 9 mmol/L) may improve immediate graft function in 
this patient population. 
 
 

                                                                                                                                                                          
Dept. of Anesthesiology and Pain Medicine   TGH                                                         
PDF Trial 
 
 
Study protocol – Version 1.0 
March 27, 2024 
 
Page 9 of 15 
 
4.2 Study 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.  
 
5. STUDY OBJECTIVES (HYPOTHESIS) 
We hypothesize that the proposed perioperative bundle of care will be feasible to 
implement and improve postoperative outcomes for kidney transplant recipients.  
5.1 Primary Objective 
To determine the feasibility of recruiting and randomizing kidney transplant recipients 
to an RCT evaluating the administration of a perioperative bundle of care. 
5.2 Secondary Objectives 
To determine protocol adherence and follow-up rates.   
 
6. STUDY DESIGN 
6.1 Study type  
Randomized controlled feasibility trial  
6.2 Study population 
Patients ≥18 years of age undergoing kidney transplantation at Toronto General 
Hospital (TGH).  
6.2.1 Department 
The study will be conducted by the Department of Anesthesia and Pain Management 
and the Department of Transplant Nephrology, Ajmera Transplant Centre at the 
Toronto General Hospital, University Health Network.   
6.2.2 Subjects 
Patients who are admitted to hospital to undergo KT at TGH. Patients will be screened 
for eligibility and included in the study if the criteria listed below are met:  
6.2.3 Inclusion criteria 
• ≥ 18 years 
• Patients undergoing kidney transplantation  
• Living and deceased donor recipients  

                                                                                                                                                                          
Dept. of Anesthesiology and Pain Medicine   TGH                                                         
PDF Trial 
 
 
Study protocol – Version 1.0 
March 27, 2024 
 
Page 10 of 15 
 
6.2.4 Exclusion criteria 
• Multi-organ transplant  
• Pre-emptive KT 
• Arterial line not planned for surgery 
6.2.5 Study duration 
We anticipate completing data collection, cleaning, and analysis by the end of 
December 2025. 
6.3 Outcomes  
6.3.1 Primary outcomes 
Our primary outcome is the feasibility of implementing a perioperative bundle of care 
for KT patients. The specific outcome is: 
• Recruitment rate, which will be 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. 
 
6.3.2 Secondary outcomes  
• 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.   
• Patient follow-up. 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.   
 
6.3.3 Covariates 
 
• Baseline patient factors: age, sex, height and weight  
• Transplant details: graft type (deceased or living donor), kidney donor prediction 
index (KDPI)31 etiology of kidney failure, transplant number, preoperative 
hemoglobin optimization strategies (iron, erythroid stimulating agents), previous 
blood transfusion, method and duration of pre-transplant dialysis.  
• Comorbidities: previous abdominal surgery, coronary artery disease, heart 
failure, cardiomyopathy, hypertension, diabetes mellitus (diet, oral medications 
or insulin control), chronic obstructive pulmonary disease, smoking history, 
medications including anticoagulants and anti-platelets.  
• Immediate preoperative laboratory values: hemoglobin, hematocrit, platelet 
count, INR, albumin, ferritin, iron saturation, glucose and creatinine.  

                                                                                                                                                                          
Dept. of Anesthesiology and Pain Medicine   TGH                                                         
PDF Trial 
 
 
Study protocol – Version 1.0 
March 27, 2024 
 
Page 11 of 15 
 
7. METHODOLOGY 
7.1 Screening and inclusion 
Eligible patients will be identified by a member of the perioperative clinical transplant 
team. Surgical consent includes consent for research activities, which provides the 
transplant team member the opportunity to ask the patient if a member of the study 
team can discuss the study details and potential participation. Informed consent to 
participate in the study will be obtained from the patient by a study team member or 
member of the patient’s circle of care after admission for KT. Patients are typically 
admitted 12-36 hours prior to KT, however we will ensure patients are consented at a 
minimum of 6 hours prior to KT for study participation. This provides the necessary 
time to allow the patient to consider participation, to randomize study participants, and 
communicate with the transplant team regarding the patient’s group allocation.   
7.2 Sample size considerations 
Based on our transplant activity over the last several years, we conduct an average of 
at least 5 KTs per week. We expect 40% of eligible patients to be recruited for the 
study, based on a similar trial and patient population.23 A sample size of 25 patients 
per group will provide sufficient statistical power to be within the 95% confidence 
interval if we are able to recruit a total of 43-57 patients within 1-year (50 weeks). 
Furthermore, this sample size will provide a 95% confidence interval of ~70% to ~98% 
around the expected ≥90% compliance with the study protocol and ≥90% complete 
follow-up 90-days post KT.  
7.3 Data sources 
EPIC.  
7.4 Study intervention  
Patients will be randomized 1:1 to either routine care or to the treatment group. The 
treatment group will receive a perioperative bundle of care that will be a modified 
version of the KDIGO guidelines and will include: use of Plasmalyte for fluid 
management, maintenance of MAP >75 mmHg, identifying and treating blood sugar 
> 9 mmol/L, and avoidance of RBC transfusion unless the hemoglobin < 70 g/L or 
symptoms of oxygen insufficiency and hemoglobin < 80 g/L.   
 
7.5 Statistical methods and endpoints analysis 
Categorical variables will be summarized as frequencies and percentages; continuous 
variables as means with standard deviation. The unadjusted association of potential 
predictors of the secondary outcomes will be evaluated for both continuous (t test, 
Wilcoxon rank sum test) and categorical (χ2 test, Fisher’s exact test, Mantel-Haenszel 
χ2 test) variables. Independent predictors of the secondary outcomes will be identified 
by multivariable logistic regression analysis.  
 
7.6 Statistical software 
SPSS, R studio, and SAS.  

                                                                                                                                                                          
Dept. of Anesthesiology and Pain Medicine   TGH                                                         
PDF Trial 
 
 
Study protocol – Version 1.0 
March 27, 2024 
 
Page 12 of 15 
 
7.7 Data management   
All study data will be kept on secure, password-protected storage media, and with 
restricted access at the Department of Anesthesiology and Pain Medicine and 
Transplant Nephrology, at TGH. Only research personnel involved in the study will 
have access to the study data. The files resulting from the data analysis will be 
password protected. A Participant Master Log will be maintained with the participant's 
MRNs to facilitate data collection. The Participant Master List will be kept securely on 
a password-protected storage platform, UHN One Drive. Apart from the participant 
Master List, all data will be pseudonymized using an independent study ID before 
analysis and de-identified before publishing. Study data and all files resulting from the 
analysis will be kept on UHN One Drive for 10 years after the conclusion of the study.  
 
8. ETHICAL AND LEGAL ASPECTS 
8.1 Informed consent 
A transplant team member will identify eligible patients who present on admission for 
KT. If deemed eligible, the transplant team member will inform the patient of the study, 
and ask if a member of the study or transplant team can discuss the study details and 
potential participation. If the patient is willing to participate, the study or transplant team 
member will obtain informed consent from the patient.   
8.2 Confidentiality  
The information contained in this document, especially unpublished data, is the 
property of the Investigators. It is therefore provided to you in confidence as an 
Investigator, potential Investigator, or consultant for review by you, your staff, and an 
Ethics Committee or Institutional Review Board. It is understood that this information 
will not be disclosed to others without written authorization from an Investigator. 
8.3 Ethics and Good Scientific Practice  
The investigators will ensure that this study is conducted in full conformance with the 
principles of the "Declaration of Helsinki" (as amended at the 64th WMA General 
Assembly, Fortaleza, Brazil, 2013) and with the laws and regulations of the country in 
which the clinical research is conducted.  
8.4 Benefit and risk assessment 
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. 
This study poses a potential risk to study participants, as it will impact their care. Firstly, 
MAP will be maintained >75 mmHg, which is a ~10 mmHg difference above the current 
MAP standard of care (i.e., 65 mmHg). For the second component, normal saline is a 
routinely used fluid for kidney transplants, but instead patients will receive plasmalyte. 
For the third component, the patient’s clinical care team will avoid hyperglycemia in the 

                                                                                                                                                                          
Dept. of Anesthesiology and Pain Medicine   TGH                                                         
PDF Trial 
 
 
Study protocol – Version 1.0 
March 27, 2024 
 
Page 13 of 15 
 
72h post-transplant. Although this should be completed in routine clinical care, we are 
directly specifying the patient’s blood glucose will be maintained <9 mmol/L. For the 
final component of the care bundle, we would ask the surgical care team to avoid RBC 
transfusions, and to only transfuse if the hemoglobin falls below 70 g/L or a symptom 
that indicates inadequate oxygen delivery is present. Although kidney transplants are 
associated with a relatively low amount of blood loss, and 30-50% of patients receive 
1-2 units of RBCs, we are asking the surgical care team to follow a restrictive protocol 
with the administration of RBC transfusions. 
Patients will be informed that the control group will consist of routine clinical care, (i.e., 
what is routine KT surgery) while the treatment arm will receive a bundle of care which 
may potentially support the health of their new kidney.  
All data will be de-identified before analysis and publishing, and all precautions will be 
taken to ensure data security, privacy, and confidentiality.  
9. FINANCIAL ASPECTS 
The Funds for the Fraser Elliot Chain in Cardiac Anesthesia and Department of 
Anesthesia and Pain Management is the sponsor of this study. Internal funding set 
aside. A detailed budget can be found below.  
 
Category 
Detailed Breakdown 
Anticipated 
Funding 
Need 
Personnel 
Research Coordinator - $81,250 per annum 
inclusive of benefits, at 0.5 full-time equivalent  
$40,625 
Database 
REDCAP build 
$2,000 
Statistical 
analysis 
35 hours x $100 
$3,500 
Research 
Publication 
Open Access Publication Costs, Conference 
Registration, and Knowledge Dissemination 
$3,800 
Other Costs 
Stationary, paper for CRFs 
$  400 
Total Anticipated Costs 
$49,929 
 
 
 
 
 

                                                                                                                                                                          
Dept. of Anesthesiology and Pain Medicine   TGH                                                         
PDF Trial 
 
 
Study protocol – Version 1.0 
March 27, 2024 
 
Page 14 of 15 
 
 
10. REFERENCES 
1. 
Abecassis M, Bartlett ST, Collins AJ, et al. Kidney transplantation as primary therapy for end-
stage renal disease: a National Kidney Foundation/Kidney Disease Outcomes Quality Initiative 
(NKF/KDOQI™) conference. Clinical Journal of the American Society of Nephrology 2008;3:471-80. 
2. 
Cecka JM. The UNOS renal transplant registry. Clinical transplants 2002:1-20. 
3. 
Shoskes D, Cecka J. Effect of delayed graft function on short-and long-term kidney graft 
survival. Clinical transplants 1997:297-303. 
4. 
Mannon RB. Delayed Graft Function: The AKI of Kidney Transplantation. Nephron 
2018;140:94-8. 
5. 
Mendez NV, Raveh Y, Livingstone JJ, et al. Perioperative risk factors associated with delayed 
graft function following deceased donor kidney transplantation: A retrospective, single center study. 
World journal of transplantation 2021;11:114. 
6. 
Grosso G, Corona D, Mistretta A, et al. Delayed graft function and long-term outcome in 
kidney transplantation. Transplant Proc 2012;44:1879-83. 
7. 
Wu WK, Famure O, Li Y, Kim SJ. Delayed graft function and the risk of acute rejection in the 
modern era of kidney transplantation. Kidney Int 2015;88:851-8. 
8. 
Damodaran S, Bullock B, Ekwenna O, et al. Risk factors for delayed graft function and their 
impact on graft outcomes in live donor kidney transplantation. International urology and nephrology 
2021;53:439-46. 
9. 
Kinoshita Y, Katano S, Nishida S, et al. Creatinine reduction ratio on postoperative day 2 
predicts long‐term outcomes after living donor kidney transplantation. International Journal of 
Urology 2022;29:114-20. 
10. 
Rodrigo E, Ruiz JC, Piñera C, et al. Creatinine reduction ratio on post-transplant day two as 
criterion in defining delayed graft function. American Journal of Transplantation 2004;4:1163-9. 
11. 
Vilar E, Varagunam M, Yaqoob MM, Raftery M, Thuraisingham R. Creatinine reduction ratio: 
a useful marker to identify medium and high-risk renal transplants. Transplantation 2010;89:97-103. 
12. 
Govani MV, Kwon O, Batiuk TD, Milgrom ML, Filo RS. Creatinine reduction ratio and 24-hour 
creatinine excretion on posttransplant day two: simple and objective tools to define graft function. J 
Am Soc Nephrol 2002;13:1645-9. 
13. 
Li MT, Ramakrishnan A, Yu M, et al. Effects of Delayed Graft Function on Transplant 
Outcomes: A Meta-analysis. Transplantation Direct 2023;9:e1433. 
14. 
Gaston RS, Danovitch GM, Adams PL, et al. The report of a national conference on the wait 
list for kidney transplantation. American Journal of Transplantation 2003;3:775-85. 
15. 
Clayton LM, Rizzolo D, Nair V. Kidney transplant wait list: review and current trends. JAAPA 
2018;31:1-5. 
16. 
Kinoshita Y, Katano S, Nishida S, et al. Creatinine reduction ratio on postoperative day 2 
predicts long-term outcomes after living donor kidney transplantation. Int J Urol 2022;29:114-20. 
17. 
Meersch M, Schmidt C, Hoffmeier A, et al. Prevention of cardiac surgery-associated AKI by 
implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI 
randomized controlled trial. Intensive care medicine 2017;43:1551-61. 
18. 
Zarbock A, Küllmar M, Ostermann M, et al. Prevention of cardiac surgery–associated acute 
kidney injury by implementing the KDIGO guidelines in high-risk patients identified by biomarkers: 
The PrevAKI-multicenter randomized controlled trial. Anesthesia & Analgesia 2021;133:292-302. 
19. 
Tan JHS, Bhatia K, Sharma V, et al. Enhanced recovery after surgery recommendations for 
renal transplantation: guidelines. Br J Surg 2022;110:57-9. 
20. 
Kruszyna T, Niekowal B, Krasnicka M, Sadowski J. Enhanced Recovery After Kidney 
Transplantation Surgery. Transplant Proc 2016;48:1461-5. 

                                                                                                                                                                          
Dept. of Anesthesiology and Pain Medicine   TGH                                                         
PDF Trial 
 
 
Study protocol – Version 1.0 
March 27, 2024 
 
Page 15 of 15 
 
21. 
Elsabbagh AM, Ghoneim I, Moiz A, Welch K, Brown JS. Enhanced Recovery After Surgery 
Pathway in Kidney Transplantation: The Road Less Traveled. Transplant Direct 2022;8:e1333. 
22. 
Sandid MS, Assi MA, Hall S. Intraoperative hypotension and prolonged operative time as risk 
factors for slow graft function in kidney transplant recipients. Clinical transplantation 2006;20:762-8. 
23. 
Collins MG, Fahim MA, Pascoe EM, et al. Balanced crystalloid solution versus saline in 
deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, 
controlled trial. The Lancet 2023;402:105-17. 
24. 
Rodriguez-Espinosa D, Broseta JJ, Rosario A, et al. Challenges in perioperative blood 
transfusions in kidney transplantation and the need for Patient Blood Management. Blood Transfus 
2023. 
25. 
Kang ZY, Liu C, Liu W, Li D. Association between blood transfusion after kidney 
transplantation and risk for the development of de novo HLA donor-specific antibodies and poor 
clinical outcomes: A single-center retrospective study. Transpl Immunol 2023;81:101930. 
26. 
O'Brien FJ, Lineen J, Kennedy CM, et al. Effect of perioperative blood transfusions on long 
term graft outcomes in renal transplant patients 
1. ClinNephrol 2012;77:432-7. 
27. 
Hassan S, Mumford L, Robinson S, et al. Blood transfusions post kidney transplantation are 
associated with inferior allograft and patient survival-it is time for rigorous patient blood 
management. Front Nephrol 2023;3:1236520. 
28. 
Hassan S, Mumford L, Robinson S, et al. Blood transfusions post kidney transplantation are 
associated with inferior allograft and patient survival—it is time for rigorous patient blood 
management. Frontiers in Nephrology 2023;3. 
29. 
Parekh J, Roll GR, Feng S, Niemann CU, Hirose R. Peri‐operative hyperglycemia is associated 
with delayed graft function in deceased donor renal transplantation. Clinical transplantation 
2013;27:E424-E30. 
30. 
Collins MG, Fahim MA, Pascoe EM, et al. Balanced crystalloid solution versus saline in 
deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, 
controlled trial. Lancet 2023;402:105-17. 
31. 
Rao PS, Schaubel DE, Guidinger MK, et al. A comprehensive risk quantification score for 
deceased donor kidneys: the kidney donor risk index. Transplantation 2009;88:231-6.