Background: We have previously shown that autoantibodies to the LG3 fragment of perlecan enhance vascular damage in a murine model of vascular rejection, particularly when the allograft is exposed to ischemia prior to transplantation. The aim of the present study is to assess whether pre-transplant anti-LG3 antibodies increase the risk for delayed graft function (DGF) or slow graft function (SGF) in kidney transplant recipients, and whether they are associated with poorer graft function on follow-up.

Methods: We performed a retrospective cohort study among consecutive kidney transplant recipients who received a kidney allograft at our center between January 1st, 2008 and June 1st, 2013. Anti-LG3 IgG antibodies were measured on pre-transplant sera using a locally-developed ELISA. DGF was defined as the need for dialysis in the first post-transplant week, and SGF was defined as failure of serum creatinine to decrease by more than 10% on the first 3 post-operative days or serum creatinine levels >240 umol/L on post-operative day 5. Logistic and linear regressions were used to assess the relationships between pre-transplant anti-LG3 titers and DGF/SGF or graft function 1 month post-transplant.

Results: Among the 173 patients included in this study, 52 patients experienced DGF/SGF. In a multivariate logistic regression model, pre-transplant anti-LG3 levels were independently associated with DGF/SGF (odds ratio (OR): 1.32 for a 100 unit increase, 95% confidence interval (CI): 1.06-1.63). Other factors that increased the risk of DGF/SGF were donor type (donor after cardiac arrest compared to living (OR: 13.53, 95% CI: 2.17-84.54), deceased donor compared to living (OR: 2.92, 95% CI: 1.28-6.64)). In patients with DGF/SGF, decreased graft function 1 month after transplantation was associated with elevated pre-transplant anti-LG3 titers (β:-0.33 ln ml/min/1.73m2, 95% CI: -0.59, -0.07 for 3rd versus 1st tertile) and donor age≥ 60 years (β:-0.32 ln ml/min/1.73m2, 95% CI: -0.56, -0.08 ). In contrast, there was no association between anti-LG3 titers and graft function in patients who had not experienced DGF/SGF.

Conclusion: Our results show that anti-LG3 antibodies are associated with an increased risk of DGF/SGF, and correlate with poorer graft function in this group of patients. These results are in keeping with an aggravating role for anti-LG3 autoantibodies on vascular damage associated with ischemia-reperfusion injury.

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