Session Time: 4:00pm-5:30pm
Presentation Time: 4:00pm-4:12pm
Location: Room 120-ABC
Historically, dialysis required in the first post-transplant (TX) week has defined DGF. This incidence-based definition fails to discriminate between short versus long courses of dialysis and their respective outcomes. Just as DGF Risk predicts graft loss (Irish AJT, 2010), increasing number of dialysis treatments (DRxs), an intuitive measure defining DGF Severity, has been associated with increased risk of TX complications and graft loss (Buchanan J NephTher, 2011; Akkina AJT, 2009).The relationship of DGF Risk and DGF Severity has not previously been explored. Methods: A multicenter, placebo-controlled trial of QPI-1002, a siRNA targeting p53, for prophylaxis of DGF (Peddi Am J Transpl, 2014) randomized 327 subjects [Placebo (PBO)/QPI-1002:163/164]. A Loess scatterplot of DGF Risk and DGF Severity was performed and confirmed using a negative binomial regression model (NBRM).Donor age>45 subgroup was also analyzed given increased p53 expression in older kidneys. Results: For the PBO group mean (range) number of DRxs per subject was 2 (0-15); 24% (n=39) of PBO subjects had ≥3 DRxs. Mean DGF risk ranged from 28.8% for PBO subjects with 0 DRxs to 50.9% for PBO subjects with ≥3 DRxs. Expected number of DRxs (adjusted for pre-stratification factors) increased by 4.60(SE 0.44) (loge scale) per unit increase in DGF risk (95%CI 3.74-5.46; p<0.001). Using the DGF Risk NBRM, QPI-1002 mitigated the expected rise in DRxs per unit of DGF Risk to 2.07(SE 0.899) [(95%CI 0.31, 3.83)p=0.021: a 55% relative slope reduction (Figure).In TX with donors age >45, compared to PBO (N=127), QPI-1002 (N=126) significantly reduced total post TX DRXs (from 293 (mean=2.1) to 143 (mean1.1); p=0.006). Conclusions: In a large randomized DGF study, QPI-1002 significantly reduced the effect of the DGF Risk score on DGF severity and significantly reduced DGF severity in donors >45 years. A NBRM model confirms the relationship between DGF risk and DGF severity, supporting publications that found DGF severity to be predictive of graft survival. The current analysis suggests that DGF severity is a useful endpoint in clinical trials of DGF.
To cite this abstract in AMA style:Squiers E, Irish B, Odenheimer D, Erlich S, Grinyo J, Feng S. Relationship Between Delayed Graft Function (DGF) Severity and Predicted DGF Risk [abstract]. Am J Transplant. 2015; 15 (suppl 3). http://atcmeetingabstracts.com/abstract/relationship-between-delayed-graft-function-dgf-severity-and-predicted-dgf-risk/. Accessed April 28, 2017.
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