Delayed Graft Function: Where Do We Stand?

Detailed reviews of treatment options for delayed graft function following kidney transplantation are lacking despite numerous randomized trials in the last few years. Dr. Richard Borrows (RB), the corresponding author of a recent review published in the American Journal of Kidney Diseases, discusses this topic with Dr Tejas Desai (eAJKD), eAJKD Advisory Board member.

eAJKD: What were the major surprises during your review of this topic?

RB: Risk stratification based on clinical measures has been the strategy used at many centers to predict outcomes of delayed graft function (DGF). Many authors looked at developed risk scores and predictive nomograms based on urinary and serum biomarkers to predict delayed graft function. Interestingly, neither the composite measures nor the individual biomarkers predicted at individual graft outcomes. That finding was disappointing.

eAJKD: Did you find any positive findings during your review?

RB: Compared to other fields in nephrology, the number of randomized control trials that have been done in this area is very impressive. In addition, it was an educational experience for us to learn that DGF is not merely a reflection of hypotension, hypoperfusion, and ischemic injury, but also the activation of innate and possibly adaptive immunity within the recipient that is important.

eAJKD: The definition of DGF used in the article is “failure of serum creatinine to drop by 10% on three consecutive days during the first post-operative week.” Were there any other definitions that you were considering, and why did you pick this one?

RB: Although DGF is traditionally defined as the need for dialysis in the first week post-transplantation, we found 18 other unique definitions of DGF in the literature. The dialysis-based definition and the “functional DGF” definition (mention above) were the two forerunners. The dialysis-based definition is criticized for its subjectivity, and whether dialysis requirement reflects true allograft function or clinician practice. When compared with the dialysis-based definition, earlier studies showed that DGF, but not dialysis requirement, was independently associated with subsequent death-censored graft failure. We used the “functional” DGF as our standard definition.

eAJKD: What are your thoughts on the how the dialysis-based definition of DGF and the “functional” definition of DGF compare?

RB: The need for dialysis as a part of the definition is a really useful metric in some cases because it gives one the idea that graft function is inadequate in the early stages following transplantation, especially in the living related transplantation cases. The “functional” definition allows us to look at the performance of the kidneys. Sometimes, dialysis is utilized for volume-related concerns even though graft function is doing relatively well. The choice of using dialysis might have been the physician preference.

The “functional” definition allows a more objective assessment of early allograft performance then the traditional dialysis-based definition. Unquestionably, the dialysis-based definition has the most literature behind it. But we think after the “functional” definition has a good following and is a better definition. Having said that, the dialysis-based definition is also important because dialysis makes clinical care difficult and adds to cost and length of stay.

eAJKD: What excites you when it comes to experimental strategies for minimizing DGF in expanded criteria of donor kidney?

RB: I don’t think I can comment on expanded criteria donor kidney specifically because not all the trials have looked at that. Two strategies that excite me are machine perfusion as controlled trials suggest less DGF and better overall graft survival. And as a subtext to that, the emergence of normothermic perfusion suggests one can improve kidney function. The second strategy that excites me relates to pharmacologic strategies that focus on pathways that are involved in ischemia reperfusion injuries. These are small molecules administered orally or intravenously that are being investigated.

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