Redefining Delayed Graft Function: From Binary to Dynamic Using a Trajectory-Based Model to Evaluate Renal Recovery After Kidney Transplantation.
- 1Cleveland Clinic Florida
Abstract
BackgroundDelayed graft function (DGF) is among the most used metrics in transplant medicine, yet its prevailing definition-dialysis requirement within the first seven postoperative days lacks granularity and fails to capture the dynamic nature of graft recovery. It reflects a treatment decision rather than graft biology, varies by centre practice, and offers no temporal information about the pace or pattern of recovery. This study proposes a trajectory-based framework using serial serum creatinine measurements across three biologically defined time windows to capture the dynamic nature of early renal recovery.
MethodsWe retrospectively analysed 205 adult kidney transplant recipients at Cleveland Clinic Weston Hospital in 2025. Donor groups included living donors, donation after brain death (DBD), donation after circulatory death with normothermic regional perfusion (DCD-NRP), and DCD without NRP. Creatinine slopes were estimated for Days 1-7, 7-30, and 30-90 using ordinary least-squares regression. Logistic regression assessed the predictive performance of each trajectory window for DGF, adjusting for Kidney Donor Profile Index, cold ischemia time, BMI, and donor type.
ResultsDCD non-NRP kidneys showed negligible early creatinine decline (slope +0.02) compared to DBD (-0.71) and DCD-NRP (-0.57) grafts during Days 1-7. During Days 7-30, DCD-NRP kidneys showed accelerated recovery and converged toward DBD-level trajectories, whereas DCD non-NRP grafts remained sluggish. Predictive modelling identified the Day 7-30 trajectory had the strongest discrimination for DGF, with AUC 0.83, pseudo-R2 0.25, and the lowest AIC (181.73), outperforming Days 1-7 (AUC 0.75) and 30-90 (AUC 0.79). DGF rates were 0% in living donors, 25.5% in DBD, 20.7% in DCD-NRP, and 58.9% in DCD non-NRP recipients.
ConclusionsA trajectory-based creatinine model provides more informative prognostic value than the conventional binary DGF definition The Day 7-30 window periods offers the highest discriminatory power, and normothermic regional perfusion appears to favourably shift DCD kidney recovery trajectories in a manner the binary definition fails to detect.
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BibTeX
@misc{makki2026redefining,
title = {{Redefining Delayed Graft Function: From Binary to Dynamic Using a Trajectory-Based Model to Evaluate Renal Recovery After Kidney Transplantation.}},
author = {M. M. Makki and K. Kumar and D. Harutyun and J. Kusakabe and E. Fernandes and A. Pinna and K. Refaai},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.04.26362581},
url = {https://www.medrxiv.org/content/10.64898/2026.10.04.26362581v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Redefining Delayed Graft Function: From Binary to Dynamic Using a Trajectory-Based Model to Evaluate Renal Recovery After Kidney Transplantation.
AU - M. M. Makki
AU - K. Kumar
AU - D. Harutyun
AU - J. Kusakabe
AU - E. Fernandes
AU - A. Pinna
AU - K. Refaai
PY - 2026
DA - 2026/10/04
PB - medRxiv
DO - 10.64898/2026.10.04.26362581
UR - https://www.medrxiv.org/content/10.64898/2026.10.04.26362581v1
AB - BackgroundDelayed graft function (DGF) is among the most used metrics in transplant medicine, yet its prevailing definition-dialysis requirement within the first seven postoperative days lacks granularity and fails to capture the dynamic nature of graft recovery. It reflects a treatment decision rather than graft biology, varies by centre practice, and offers no temporal information about the pace or pattern of recovery. This study proposes a trajectory-based framework using serial serum creatinine measurements across three biologically defined time windows to capture the dynamic nature of early renal recovery. MethodsWe retrospectively analysed 205 adult kidney transplant recipients at Cleveland Clinic Weston Hospital in 2025. Donor groups included living donors, donation after brain death (DBD), donation after circulatory death with normothermic regional perfusion (DCD-NRP), and DCD without NRP. Creatinine slopes were estimated for Days 1-7, 7-30, and 30-90 using ordinary least-squares regression. Logistic regression assessed the predictive performance of each trajectory window for DGF, adjusting for Kidney Donor Profile Index, cold ischemia time, BMI, and donor type. ResultsDCD non-NRP kidneys showed negligible early creatinine decline (slope +0.02) compared to DBD (-0.71) and DCD-NRP (-0.57) grafts during Days 1-7. During Days 7-30, DCD-NRP kidneys showed accelerated recovery and converged toward DBD-level trajectories, whereas DCD non-NRP grafts remained sluggish. Predictive modelling identified the Day 7-30 trajectory had the strongest discrimination for DGF, with AUC 0.83, pseudo-R2 0.25, and the lowest AIC (181.73), outperforming Days 1-7 (AUC 0.75) and 30-90 (AUC 0.79). DGF rates were 0% in living donors, 25.5% in DBD, 20.7% in DCD-NRP, and 58.9% in DCD non-NRP recipients. ConclusionsA trajectory-based creatinine model provides more informative prognostic value than the conventional binary DGF definition The Day 7-30 window periods offers the highest discriminatory power, and normothermic regional perfusion appears to favourably shift DCD kidney recovery trajectories in a manner the binary definition fails to detect.
ER -