From the Guidelines
Delayed graft function (DGF) in kidney transplantation is primarily caused by ischemia-reperfusion injury, and the use of buffered crystalloid solutions instead of 0.9% saline can reduce the incidence of DGF, as shown in a recent multicentre trial 1. The pathophysiology of DGF involves cellular damage from reactive oxygen species generated during reperfusion, inflammatory responses, and microvascular injury leading to reduced blood flow to the kidney. Several factors contribute to DGF, including:
- Prolonged cold ischemia time (the period the kidney is stored in cold preservation solution)
- Donor factors (such as advanced age, hypertension, or diabetes)
- Recipient factors (like pre-existing sensitization) Additionally, brain death in deceased donors triggers inflammatory cascades that can predispose the kidney to injury. Management of DGF involves supportive care with dialysis until kidney function recovers, careful monitoring of immunosuppression (particularly avoiding nephrotoxic levels of calcineurin inhibitors), and vigilance for complications such as acute rejection, which can occur concurrently with DGF. Prevention strategies include:
- Minimizing cold ischemia time
- Using machine perfusion for organ preservation
- Optimizing donor management before procurement
- Using buffered crystalloid solutions instead of 0.9% saline, as recommended by the international multidisciplinary perioperative quality initiative 1.
From the FDA Drug Label
There was no difference in the rate of delayed graft function, patient survival, or graft survival between Simulect-treated patients and placebo-treated patients in either study. The FDA drug label does not answer the question.
From the Research
Causes of Delayed Graft Function (DGF) in Kidney Transplantation
- Factors related to the donor and prerenal, renal, or postrenal transplant factors related to the recipient can contribute to DGF 2
- Ischaemia and reinstitution of blood flow in ischaemically damaged kidneys after hypothermic preservation can activate a complex sequence of events that sustain renal injury and play a pivotal part in the development of DGF 2
- Absence of perioperative saline loading and patient's residual diuresis ≤500 mL/d are novel risk factors for DGF 3
- Ischemia-reperfusion injury is the predominant factor inducing DGF, and perioperative saline loading can efficiently prevent it 3
- Defective postreperfusion metabolic recovery, characterized by mitochondrial damage, is a primary driver of ischemia reperfusion injury and DGF 4
- Cold ischemic time, human leukocyte antigen mismatch, donor age, panel reactive antibody, recipient diabetes, donor and recipient body mass index, recipient race and gender, right nephrectomy, open nephrectomy, dialysis status, ABO incompatibility, and previous transplants are independent predictors of DGF in living-donor kidney transplants 5
Role of Biomarkers in DGF
- Emerging biomarkers, such as those identified through omics technologies (proteomics, metabolomics, and transcriptomics), may allow for early detection of DGF and improvement in graft management 6
- Conventional methods, such as serum creatinine and Glomerular Filtration Rate (GFR), can be complemented by novel biomarkers to evaluate renal allograft function and predict DGF 6
Impact of DGF on Graft Survival
- DGF is associated with decreased long-term survival and increased risk of acute rejection episodes 2
- Graft survival is decreased when rejection is associated with DGF 3
- Five-year graft survival among living-donor kidney transplant recipients with DGF is significantly lower compared to those without DGF 5