Prediction, prevention, and management of delayed graft function: where are we now?

Abstract

Delayed graft function (DGF) remains a major barrier to improved outcomes after kidney transplantation. High-risk transplant recipients can be identified, but no definitive prediction model exists. Novel biomarkers to predict DGF in the first hours post-transplant, such as neutrophil gelatinase-associated lipocalin (NGAL), are under investigation. Donor management to minimize the profound physiological consequences of brain death is highly complex. A hormonal resuscitation package to manage the catecholamine "storm" that follows brain death is recommended. Donor pretreatment with dopamine prior to procurement lowers the rate of DGF. Hypothermic machine perfusion may offer a significant reduction in the rate of DGF vs simple cold storage, but costs need to be evaluated. Surgically, reducing warm ischemia time may be advantageous. Research into recipient preconditioning options has so far not generated clinically helpful interventions. Diagnostic criteria for DGF vary, but requirement for dialysis and/or persistent high serum creatinine is likely to remain key to diagnosis until current work on early biomarkers has progressed further. Management centers on close monitoring of graft (non)function and physiological parameters. With so many unanswered questions, substantial reductions in the toll of DGF in the near future seem unlikely but concentrated research on many levels offers long-term promise.

Randomized Trial of Machine Perfusion Versus Cold Storage in Recipients of Deceased Donor Kidney Transplants With High Incidence of Delayed Graft Function

“…16,17 The only risk factor associated with DGF was the final donor creatinine, which perhaps reflects the overall hemodynamic instability of the donor and is a variable included in the majority of DGF prediction models. 18 Hemodynamic instability as a risk factor for DGF has also been described using more sophisticated analysis in a cohort of kidney transplants from donors after cardiac death. 19 On the other hand, continuous machine perfusion was the only variable independently associated with reduced risk of DGF.…”

Is prolonged cold ischemia a contraindication to using kidneys from acute kidney injury donors?

“…Growing use of AKI donor kidneys has raised concerns that these kidneys may sustain multiple insults including prerecovery warm ischemia that leads to an increased susceptibility to ischemia‐reperfusion injury. The cumulative severity of these insults may result in potentially higher rates of acute rejection, DGF, and primary nonfunction . Consequently, some centers are averse to consider these kidneys for transplantation, which results in delays in organ allocation and placement.…”

“…Unfortunately, many kidneys are declined by local centers because of AKI resulting in either regional or national allocation, which adds to CIT because of delays in placement and ultimate utilization. It is well established that longer CIT is associated with a higher rate of delayed graft function (DGF), which may result acute rejection, prolonged graft dysfunction, and inferior medium‐term graft survival . Prolonged CIT and elevated deceased donor SCr levels are major risk factors for kidney discard, but the interaction of these two factors is incompletely understood.…”

Analysis of local versus imported expanded criteria donor kidneys: A single‐center experience with 497 ECD kidney transplants

“…ECD kidneys evoke caution for many transplant centers, and when combined with longer CIT, attain an almost prohibitive status for some as both prolonged CIT categorization and ECD categorization have been identified as strong independent risk factors for DGF, reduced graft survival, and kidney discard . The presence of DGF is an early surrogate marker of organ quality and preservation that represents a combined response to a series of ischemic, reperfusion, inflammatory, and immunological injuries . By definition, the durability of an ECD kidney is limited and the majority of these kidneys are destined to premature obsolescence compared to SCD kidneys if they are transplanted into unselected recipients, with the graft half‐life estimated to be 6‐8 years compared to 10‐12 years with a SCD kidney .…”