Delayed Graft Function in 
Kidney Transplantation:  
Developing Drugs for 
Prevention 
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
July 2019 
Clinical/Medical 
   
Delayed Graft Function in 
Kidney Transplantation:  
Developing Drugs for 
Prevention  
Guidance for Industry 
 
Additional copies are available from: 
 
Office of Communications, Division of Drug Information 
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD  20993-0002  
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https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs 
 
and/or 
 
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https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-
guidances 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
July 2019 
Clinical/Medical 
   
TABLE OF CONTENTS 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND AND DEFINITIONS .......................................................................... 2 
III.  DEVELOPMENT PROGRAM ....................................................................................... 4 
A.  General Considerations ................................................................................................................. 4 
1. Efficacy Considerations ................................................................................................................... 4 
2. Safety Considerations ...................................................................................................................... 4 
B.  Specific Efficacy Trial Considerations ......................................................................................... 4 
1. Study Design, Randomization, Stratification, and Blinding ............................................................ 4 
2. Study Population and Specific Populations ..................................................................................... 5 
3. Entry Criteria ................................................................................................................................... 5 
4. Organ Storage Conditions and Use of Concurrent Immunosuppressants and Other Medications . 5 
5. Dose Selection .................................................................................................................................. 5 
6. Choice of Comparators .................................................................................................................... 6 
7. Efficacy Endpoints ........................................................................................................................... 6 
a.  Primary efficacy endpoint ......................................................................................................... 6 
b.  Secondary efficacy endpoints ................................................................................................... 7 
8. Safety Considerations ...................................................................................................................... 7 
9. Study Procedures and Timing of Assessments ................................................................................. 8 
10.  Endpoint Adjudication ................................................................................................................. 8 
11.  Statistical Considerations ............................................................................................................ 8 
12.  Accelerated Approval (Subpart H) Considerations..................................................................... 9 
13.  Risk-Benefit Considerations ........................................................................................................ 9 
REFERENCES ............................................................................................................................ 10 
 
  Contains Nonbinding Recommendations 
Delayed Graft Function in Kidney Transplantation: 
Developing Drugs for Prevention 
Guidance for Industry1 
 
 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  You 
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the 
title page.   
 
 
 
 
I.  INTRODUCTION 
 
The purpose of this guidance is to assist sponsors in the clinical development of drugs for the 
prevention of delayed graft function (DGF) in kidney transplantation.2  Specifically, this 
guidance addresses the Food and Drug Administrations (FDAs) current thinking regarding the 
overall development program and clinical trial designs for systemic drugs administered to the 
kidney transplant recipient to support an indication of prevention of DGF.   
 
This guidance does not address the treatment of DGF in the recipient or the treatment of the 
donor or the graft for the purpose of preserving or improving graft quality.  These issues may be 
addressed in separate guidances.   
 
This guidance does not contain discussion of the general issues of statistical analysis or clinical 
trial design.  Those topics are addressed in the ICH guidances for industry E9 Statistical 
Principles for Clinical Trials (September 1998) and E10 Choice of Control Group and Related 
Issues in Clinical Trials (May 2001), respectively.3 
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
                                                 
1 This guidance has been prepared by the Division of Transplant and Ophthalmology Products in the Center for 
Drug Evaluation and Research in cooperation with the Center for Biologics Evaluation and Research at the Food and 
Drug Administration.  
 
2 For purposes of this guidance, unless otherwise specified, references to drugs and drug products include drugs 
submitted for approval or approved under section 505(b) or (j) of the Federal Food, Drug, and Cosmetic Act (FD&C 
Act) and biological products licensed under section 351 of the Public Health Service Act, other than biological 
products that also meet the definition of a device in section 201(h) of the FD&C Act (21 U.S.C. 321(h)). 
 
3 We update guidances periodically.  To make sure you have the most recent version of a guidance, check the FDA 
guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents.  
1  Contains Nonbinding Recommendations 
as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
the word should in Agency guidances means that something is suggested or recommended, but 
not required. 
 
 
II.  BACKGROUND AND DEFINITIONS 
 
DGF, presenting as suboptimal renal function immediately following kidney transplantation, is a 
manifestation of ischemia-reperfusion injury (IRI) in the transplanted kidney allograft.  For the 
purpose of this guidance, DGF is defined as the need for dialysis within 7 days of 
transplantation, although other definitions and methods to assess early graft dysfunction have 
also been published (Mallon et al. 2013; Yarlagadda et al. 2008), including the following: 
 
  The need for one or more hemodialysis treatments following transplantation (not limited 
to 7 days) before the onset of graft function (Singh et al. 2011).  
 
  Days to reach a calculated estimated glomerular filtration rate of greater than or equal to 
10 milliliters (mL) per minute (min) post-transplant.  The duration of DGF was defined 
as number of days for the kidney to attain the threshold of 10 mL per min (Giral-Classe et 
al. 1998).  
 
  Creatinine reduction ratio between Day 0 and Day 7 of less than 70 percent (Johnston et 
al. 2006). 
 
DGF (and other manifestations of early graft dysfunction after transplantation) is caused by 
kidney allograft injury sustained during donor management, organ recovery, storage, 
implantation, reperfusion, and recipient-related factors.  Changes consequent to brain death in 
donors (i.e., donation after brain death (DBD)) and IRI affect organ quality.  Periods of warm 
ischemia related to hypotension and hypoperfusion during donor management and/or prolonged 
cessation of perfusion in a donor after cardiac death (DCD) cause acute injury in the allograft.  
The injuries sustained by the kidney allograft, along with subsequent innate and adaptive 
immune responses, contribute to the complex pathophysiologic mechanisms resulting in DGF.  
DGF is observed more frequently after deceased donor (including DBD and DCD) kidney 
transplantation than after living donor (LD) kidney transplantation.   
 
Although DGF episodes with different types of donors (DCD, DBD, or LD) have similar short-
term manifestations following transplantation, they may represent different pathophysiological 
processes with different long-term allograft outcomes.  As described in the published literature, 
despite higher rates of DGF and acute rejection reported in recipients of DCD kidneys compared 
to recipients of DBD or LD kidneys, subsequent survival and organ function in recipients of 
DCD kidneys with DGF may be better than in recipients of DBD kidneys with DGF (Singh et al. 
2011).  Therefore, potential treatments may have a different effect on the prevention of DGF 
after transplantations of kidneys from the different types of donors.  Overall, the outcome is 
likely to depend on the relative contribution of different donor, preservation, or recipient-related 
factors with a consequent differential response to the investigational drug.   
 
2  Contains Nonbinding Recommendations 
In addition to DGF, other grades and severities of inadequate renal function have been defined in 
the published literature, including primary nonfunction (PNF) and slow graft function (SGF) or 
functional DGF (fDGF).  
 
PNF describes the condition in which the kidney never functions adequately after 
transplantation, and the patient continues to need dialysis despite the transplant.  The diagnosis 
of PNF generally does not become established before 2 to 3 months (6090 days) after 
transplantation (Stevens et al. 2009; Woo et al. 1999). 
 
SGF or fDGF describes kidney allograft dysfunction occurring early after transplantation, but the 
dysfunction may not be severe enough to warrant dialysis.  These other forms of dysfunction 
may still portend a diminished graft and/or patient survival.  Various definitions of SGF and/or 
fDGF are used in the published literature, including the following:   
 
  fDGF defined as failure of serum creatinine level to decrease by at least 10 percent daily 
on 3 consecutive days during the first postoperative week irrespective of dialysis 
requirement (Moore et al. 2010) 
 
  SGF defined as serum creatinine greater than 3 milligrams (mg) per deciliter and no need 
for dialysis at Day 5 post-transplant (Humar et al. 1997; Humar et al. 2002)  
 
  Mild DGF defined as a serum creatinine reduction ratio from post-transplant Day 1 to 
Day 2 (CRR2) less than or equal to 30 percent plus 24-hour urine creatinine excretion 
(UC2) on Day 2 greater than 1,000 mg (Govani et al. 2002; Rodrigo et al. 2004) 
 
  Severe DGF defined as a serum CRR2 less than or equal to 30 percent plus 24-hour UC2 
on Day 2 less than or equal to 1,000 mg (Govani et al. 2002; Rodrigo et al. 2004) 
 
The main reason to prevent DGF is to avoid the need for dialysis.  Dialysis is a choice of last 
resort and puts the graft at risk because of potential hypotension, risk of thrombosis, increase in 
hospitalization, and worse clinical outcome, as reported in various publications cited above. 
 
It has further been reported that DGF is associated with adverse effect on important graft 
outcomes such as graft survival, acute rejection, and renal function (Yarlagadda et al. 2009).  A 
web-based model for predicting DGF after renal transplantation was developed using factors 
such as cold ischemia time, donor creatinine, body mass index, donation after cardiac death, and 
donor age (Irish et al. 2010).  In addition to predicting DGF, this model also predicted long-term 
graft failure, thus demonstrating an unfavorable effect of DGF (or the factors leading to DGF) on 
long-term graft survival.  Although prevention of DGF may result in long-term benefits, such as 
improved patient and graft survival, these benefits have yet to be demonstrated. 
 
 
3  Contains Nonbinding Recommendations 
III.  DEVELOPMENT PROGRAM 
 
A.  General Considerations 
 
1.  Efficacy Considerations 
 
Trials to demonstrate that treatments reduce the risk of DGF should be superiority trials in which 
an active treatment is compared to placebo because there is no approved drug that reduces the 
risk of DGF and there is no standard of care that has been demonstrated to be effective. 
 
If the drug is an unapproved drug, in general, we recommend two adequate and well-controlled 
trials to provide evidence of effectiveness.  A single adequate and well-controlled trial supported 
by confirmatory information, such as a trial in a closely related indication (e.g., based on 
mechanism of action, target receptor), could potentially provide evidence of effectiveness in the 
prevention of DGF.  A single adequate and well-controlled trial could provide evidence of 
effectiveness if the results were statistically strong and the trial had other strong features (many 
sites, consistent results).  Sponsors should discuss with the Agency the confirmatory evidence 
that could support a significant finding from a single adequate and well-controlled trial. 
 
2.  Safety Considerations 
 
In general, we recommend a preapproval safety database of 300 patients or more on the 
investigational drug.4  If the same or greater dose and duration of therapy for the prevention of 
DGF were used in clinical trials for other disease indications, the safety information from those 
clinical trials can be part of the overall preapproval safety database.  
 
For new drugs that have an important clinical benefit compared to current management 
strategies, depending on the benefit demonstrated, a smaller preapproval safety database may be 
sufficient.  Sponsors should discuss the appropriate size of the preapproval safety database with 
the Agency during clinical development. 
 
B.  Specific Efficacy Trial Considerations 
 
1.  Study Design, Randomization, Stratification, and Blinding 
 
The clinical trial population for efficacy trials should include de novo kidney transplant 
recipients and be representative of a U.S. patient population, including race, age, sex, and other 
baseline characteristics.  
 
                                                 
4 A safety database large enough to rule out a serious adverse event that occurs at the rate of 1 in 100 or higher may 
be suitable when there are limited therapeutic options.  For example, when there are no serious and unexpected 
adverse events in approximately 300 patients, then the true rate of serious and unexpected adverse events is likely to 
be fewer than 1 in 100 or 1 percent (Hanley and Lippman-Hand 1983). 
 
4  Contains Nonbinding Recommendations 
The type of donors, preferably graded by the kidney donor profile index implemented by the new 
Kidney Allocation System,5 should be specified in the protocol.  Consideration should be given 
to stratifying the study population, for example, based on study center and/or the type of 
induction treatment (if there is more than one).  If the sponsor plans to enroll recipients of the 
DCD donor kidneys or donor kidneys preserved by machine perfusion, we highly recommend 
stratification based on the type of donor (DCD versus DBD) and organ preservation method.  
 
The trials should be randomized and double-blinded. 
 
2.  Study Population and Specific Populations 
 
Enrichment strategies can be used to select a study population at a higher risk for developing 
DGF compared to the overall kidney transplant recipient population for these clinical trials, as 
discussed in the guidance for industry Enrichment Strategies for Clinical Trials to Support 
Determination of Effectiveness of Human Drugs and Biological Products (March 2019).   
 
3.  Entry Criteria 
 
The protocol should specify the inclusion and exclusion criteria that will be used to select 
patients to participate in the clinical trial, including any enrichment strategies.  
 
4.  Organ Storage Conditions and Use of Concurrent Immunosuppressants and 
Other Medications 
 
The protocol should specify the type of organ recovery, storage, and transport conditions:  
machine perfusion (cold or warm) or static cold storage.  
 
Immunosuppressive (IS) therapy after transplantation should be specified, including the 
induction regimen(s) and the maintenance therapy.  In clinical trials of DGF, the Agency highly 
recommends that the type of induction, including the initial intravenous corticosteroid boluses at 
the time of transplantation and the maintenance IS therapy, be standardized across the treatment 
groups to minimize the potential confounding effect of these factors on the study endpoints.   
 
The protocol should state that data on the IS and other medications used in the study patients 
should be collected on the case report forms (CRFs).  For drugs managed using therapeutic drug 
monitoring, drug trough levels should be collected on the CRF. 
 
5.  Dose Selection 
 
Sponsors should conduct dose-ranging studies during phase 1 or phase 2 testing.  Generally, 
trials to prevent DGF (and other forms of early graft dysfunction) would be expected to have a 
short duration of treatment, so different dosage regimens could be evaluated in the first week 
after transplantation.   
 
                                                 
5 See the U.S. Department of Health and Human Services Kidney Allocation System web page at 
https://optn.transplant.hrsa.gov/learn/professional-education/kidney-allocation-system/.  
5  Contains Nonbinding Recommendations 
6.  Choice of Comparators 
 
Trials should be placebo-controlled, as at present there are no approved therapies and no 
standard of care for the prevention of DGF. 
 
7.  Efficacy Endpoints 
 
a.  Primary efficacy endpoint 
 
Sponsors should consider the following when choosing a primary efficacy endpoint:  
 
  Short-term assessment endpoint 
 
  Short-term assessment of the graft function for efficacy  In the short-term 
assessment of the graft function, the common definition of DGF (i.e., the requirement 
for hemodialysis treatment within the first 7 days post-transplant) can be used as the 
primary endpoint.  Sponsors can also propose other definitions of DGF supported by 
literature.  
 
As an alternative to the assessment of the occurrence of DGF as a binary endpoint, 
DGF severity scoring systems can be proposed.  These could include the number of 
hemodialysis sessions required until recovery of renal function or time to recovery of 
renal function after the diagnosis of DGF.  If the DGF severity scoring endpoint is 
chosen as the primary endpoint, the sponsor should provide a justification for the 
clinical significance and relevance of the proposed score difference to be 
demonstrated.   
   
In addition to recording any hemodialysis sessions during the first 7 days post-
transplant, information on hemodialysis sessions after Day 7 until post-transplant Day 
30, regardless of the reason for dialysis, should be collected on the CRFs to evaluate 
the durability of treatment and should be submitted in the final study report. 
 
  Short-term endpoint using SGF and fDGF  Another option is to select a short-term 
primary endpoint based on definitions of suboptimal renal allograft function, such as 
SGF or fDGF.  The protocol should include the specific definition of SGF and/or 
fDGF that will be used.  If the primary endpoint definition includes a particular 
definition of renal allograft function, the sponsor should justify the clinical benefit of 
such an endpoint and the sponsor should discuss the proposed endpoint definition 
with the FDA.  Long-term clinical benefit such as an improvement in graft or patient 
survival may need to be demonstrated. 
 
  Long-term efficacy and improved renal function  If an additional goal of the clinical 
trial is to demonstrate that the drug leads to an overall sustained improvement in renal 
function, compared to placebo, then renal function data need to be collected for all 
patients for a minimum of 12 months.  A clinically meaningful difference in renal 
6  Contains Nonbinding Recommendations 
function (assessed using serum creatinine levels or glomerular filtration rate) should be 
justified before study initiation. 
 
b.  Secondary efficacy endpoints 
 
Sponsors should consider the following when choosing secondary efficacy endpoints: 
 
  DGF  If one of the DGF severity scoring methods is chosen for the primary endpoint, 
the classic definition of DGF (i.e., requirement of dialysis within the first 7 days post-
transplant) should be among the secondary endpoints  
 
  Day 30 analysis  The purpose of this analysis is to evaluate the durability of treatment 
effect after the first week post-transplant 
 
  Renal function  The comparison of renal function (measured or calculated) between 
the treatment and placebo arms at prespecified time points for 12 months post-transplant 
should be among the secondary endpoints 
 
  Definitions of SGF or fDGF can be among the secondary endpoints. 
 
8.  Safety Considerations 
 
Because dosing is expected to occur during the first week post-transplant, intensive laboratory 
testing and collection of adverse event data for 30 days of follow-up may be sufficient.  
Depending on the pharmacokinetic/pharmacodynamic (PK/PD) properties of the drug, longer 
clinical and laboratory follow-up for drug-associated adverse events could be needed.   
 
As noted above, the primary efficacy endpoint can be evaluated when data are available for the 
first 30 days post-transplant.  However, additional follow-up is needed to understand the long-
term effect of a drug to prevent DGF on the kidney allograft and patient. 
 
For this indication, the mechanism of action of the drug is related to preventing injury and 
inflammation.  The primary mechanism of action is not as an immunosuppressant (these drugs 
are not primarily intended to suppress T-cells and B-cells, per se).  However, one cannot assume 
the drug for DGF is neutral with respect to IS or other related effects (low white blood cell, 
cytomegalovirus pneumonia).  Therefore, acute rejection, graft loss, and death are not efficacy 
endpoints; rather, they are safety endpoints in trials of drugs to prevent DGF.  The reason for 
longer follow-up is to assess whether the DGF drug has an unintended effect on the kidney 
allograft (toxicity) and whether that toxicity affects the kidneys ability to function, making it 
susceptible to rejection or other injury and affecting survival (either favorably or adversely).  The 
general duration of follow-up for safety should be a minimum of 12 months, and information 
should be collected on the survival and function of the graft (including episodes of rejection), the 
occurrence of hospitalization, and other serious adverse events, patient survival at a minimum at 
Month 3 (approximately Day 90), Month 6, and Month 12, as follows:  
 
7  Contains Nonbinding Recommendations 
  Patient and graft survival  Patient and graft survival data should be among the safety 
endpoints, and data for at least 12 months post-transplant should be collected 
 
  Rejection  Acute cellular rejection and antibody mediated rejection episodes should be 
recorded on the CRFs for at least 12 months post-transplant and analyzed as part of the 
safety endpoints 
 
  Hospitalizations  Data on hospitalizations should be collected for at least 12 months 
post-transplant and analyzed as part of the safety endpoints 
 
9.  Study Procedures and Timing of Assessments 
 
The primary endpoint can be assessed at Day 7 post-transplant.  The need for dialysis between 
Day 7 and Day 30 should also be evaluated, including the number of dialysis sessions captured 
on the CRF, for assessment of the durability of treatment effect.    
 
To evaluate the comparability of the study groups, dialysis sessions in the week before transplant 
should be captured on the CRF. 
 
For the assessment of safety, information on all adverse events and laboratory tests should be 
collected for up to Day 30 for drugs with short half-lives.  However, depending on the PK 
characteristics and duration of PD effect, longer follow-up with collection of laboratory data and 
adverse event assessments may be needed. 
 
Data on the following types of serious adverse events should be collected for a minimum of 12 
months:  acute rejection, graft loss, hospitalizations (e.g., for infection, new onset diabetes after 
transplantation, neurologic adverse events, malignancies), and patient death.  All attempts should 
be made to collect these data; missing information on hospitalizations or acute rejection should 
be minimized.   
 
10.  Endpoint Adjudication 
 
There should be no endpoint adjudication, meaning that for the intent-to-treat (ITT) analysis, all 
dialysis sessions that occurred within the first 7 days post-transplant should be included in the 
analysis.  However, sponsors can perform sensitivity analyses to look at subsets of patients 
where the specific reason for the dialysis session (e.g., hypervolemia) is taken into consideration.  
These analyses can be done in addition to the ITT population analysis but should not replace it.   
 
11.  Statistical Considerations 
 
The protocol should specify how information will be collected and how it will be analyzed.  All 
patients with DGF, defined as dialysis within 7 days post-transplant, should be included as 
treatment failures in the analysis.  Patients who experience graft loss, or death, or who are lost to 
follow-up in the first 7 days should be imputed as treatment failures.  However, no patient should 
be lost to follow-up in the first 30 days post-transplant. 
 
8  Contains Nonbinding Recommendations 
The primary efficacy endpoint should be analyzed based on the ITT population, defined as all 
patients randomized who receive a kidney transplant.   
 
If the protocol specifies SGF or fDGF as part of the primary endpoint, the planned analysis 
should be specified in the protocol and statistical analysis plan (SAP).  Strategies to handle 
missing data should be defined; however (as noted above), there should be no missing data in the 
first 30 days post-transplant. 
 
If other measures of treatment success, such as severity scores or time to graft function recovery, 
are used as the primary endpoint, the protocol and SAP should describe how the results will be 
analyzed.  For patients who experience graft loss or death in the first 30 days, an appropriate 
analysis strategy should be defined (e.g., imputing three dialysis sessions per week should be 
considered when actual data are not available).   
 
As a secondary endpoint, a Day 30 analysis should look at the percentage of patients who 
received dialysis within the first 30 days post-transplant, using similar analysis strategies as for 
the primary endpoint.  This analysis is to assess durability of the treatment.  The direction and 
magnitude of the treatment effect should be comparable to the primary endpoint. 
 
Safety should be analyzed in those ITT patients who received at least one dose of the 
investigational drug or control drug (e.g., placebo) and were evaluated for acute rejection, graft 
loss, hospitalization for serious adverse events, and patient death at least at Month 3, Month 6, 
and Month 12.  
 
12.  Accelerated Approval (Subpart H) Considerations 
 
While a primary endpoint that includes prevention of hemodialysis treatment during the first 7 
days post-transplant is associated with clinical benefit and could be used to support a traditional 
approval, sponsors should discuss with the FDA plans to use any surrogate endpoints that are 
reasonably likely to predict clinical benefit to support accelerated approval.6  An accelerated 
approval pathway will require confirmation of clinical benefit through postmarketing confirmatory 
trials to verify and describe the anticipated effect on irreversible morbidity, mortality, or other 
clinical benefit.7 
 
13.  Risk-Benefit Considerations 
 
The early benefit of preventing DGF should be compared to the safety of the drug, evaluated 
directly in the first 30 days post-transplant and the effect, if any, on the subsequent rates of acute 
rejection, graft loss, serious adverse events requiring hospitalization, and patient death for a 
minimum of 12 months post-transplant.  The benefit of preventing DGF should outweigh the 
risks of treatment. 
 
                                                 
6 See section 506(c) of the FD&C Act; 21 CFR part 314, subpart H; and 21 CFR part 601, subpart E. 
 
7 See 21 CFR 314.510; 21 CFR 601.41. 
9  Contains Nonbinding Recommendations 
REFERENCES 
 
Giral-Classe M, Hourmant M, Cantarovich D, Dantal J, Blanche G, Daguin P, Ancelet D, and 
Soulillou JP, 1998, Delayed Graft Function of More Than Six Days Strongly Decreases Long-
Term Survival of Transplanted Kidneys, Kidney Int, 54(3):972978. 
 
Govani MV, Kwon O, Batiuk TD, Milgrom ML, and Filo RS, 2002, Creatinine Reduction Ratio 
and 24-Hour Creatinine Excretion on Posttransplant Day Two:  Simple and Objective Tools to 
Define Graft Function, J Am Soc Nephrol, 13(6):16451649. 
 
Hanley JA and Lippman-Hand A, 1983, If Nothing Goes Wrong, is Everything All Right? 
Interpreting Zero Numerators, JAMA, 249: 17431745. 
 
Humar A, Johnson EM, Payne WD, Wrenshall L, Sutherland DE, Najarian JS, Gillingham KJ, 
and Matas AJ, 1997, Effect of Initial Slow Graft Function on Renal Allograft Rejection and 
Survival, Clin Transplant, 11(6):6237. 
 
Humar A, Ramcharan T, Kandaswamy R, Gillingham K, Payne WD, and Matas AJ, 2002, Risk 
Factors for Slow Graft Function After Kidney Transplants:  A Multivariate Analysis, Clin 
Transplant, 16(6):425429. 
 
Irish WD, Ilsley JN, Schnitzler MA, Feng S, and Brennan DC, 2010, A Risk Prediction Model 
for Delayed Graft Function in the Current Era of Deceased Donor Renal Transplantation, Am J 
Transplant, 10:22792286. 
 
Johnston O, OKelly P, Spencer S, Donohoe J, Walshe JJ, Little DM, Hickey D, and Conlon PJ, 
2006, Reduced Graft Function (With or Without Dialysis) vs Immediate Graft Function  A 
Comparison of Long-Term Renal Allograft Survival, Nephrol Dial Transplant, 21:22702274. 
 
Mallon DH, Summers DM, Bradley JA, and Pettigrew GJ, 2013, Defining Delayed Graft 
Function After Renal Transplantation:  Simplest Is Best, Transplantation, 96(10):885889. 
 
Moore J, Shabir S, Chand S, Bentall A, McClean A, Chan C et al., 2010, Assessing and 
Comparing Rival Definitions of Delayed Renal Allograft Function for Predicting Subsequent 
Graft Failure, Transplantation, 90(10):11131116. 
 
Rodrigo E, Ruiz JC, Pinera C et al., 2004, Creatinine Reduction Ratio on Posttransplant Day 
Two as Criterion in Defining Delayed Graft Function, Am J Transplant, 4:11631169. 
 
Singh RP, Farney AC, Rogers J, Zuckerman J, Reeves-Daniel A, Hartmann E, Iskandar S, 
Adams P, and Stratta RJ, 2011, Kidney Transplantation From Donation After Cardiac Death 
Donors:  Lack of Impact of Delayed Graft Function on Post-Transplant Outcomes, Clin 
Transplant, 25(2):255264. 
 
Stevens RB, Skorupa JY, Rigley TH, Yannam GR, Nielsen KJ, Schriner ME, Skorupa AJ, 
Murante A, Holdaway E, and Wrenshall LE, 2009, Increased Primary Non-Function in 
10  Contains Nonbinding Recommendations 
Transplanted Deceased-Donor Kidneys Flushed With Histidine-Tryptophan-Ketoglutarate 
Solution, Am J Transplant, 9(5):10551062. 
 
Woo YM, Jardine AG, Clark AF et al., 1999, Early Graft Function and Patient Survival 
Following Cadaveric Renal Transplantation, Kidney Int, 55 (2):69299. 
 
Yarlagadda SG, Coca SG, Formica Jr RN, Poggio ED, and Parikh CR, 2009, Association 
Between Delayed Graft Function and Allograft and Patient Survival:  A Systematic Review and 
Meta-Analysis, Nephrol Dial Transplant, 24:10391047. 
 
Yarlagadda SG, Coca SG, Garg AX, Doshi M, Poggio E, Marcu RJ, and Parikh CR, 2008, 
Marked Variation in the Definition and Diagnosis of Delayed Graft Function:  A Systematic 
Review, Nephrol Dial Transplant, 23:29953003.  
11