For our first aim, the outcome was the occurrence of DGF, which was defined as the need for dialysis in the first post-transplant week, failure of serum creatinine to decrease by more than 10% within the first 3 post-operative days or serum creatinine above 250 µmol/L on post-operative day 5 with evidence of acute tubular necrosis on the allograft scintigraphy (1 (link),10 (link)). The exposure, or main independent variable of interest, was high pre-transplant anti-LG3 antibody levels. High anti-LG3 was defined as a value in the highest quartile of the distribution (17 (link)). Anti-LG3 was measured with a locally-developed enzyme-linked immunosorbent assay (17 (link)). As potential interactions between anti-LG3 levels and ischemia/endothelial injury were suggested by our prior animal studies (17 (link)), we defined, a priori, use of hypothermic perfusion machine as an effect modifier to be tested. In the province of Quebec, the only pump available in the field of transplantation is hypothermic perfusion with LifePort® devices, which do not provide oxygenation. There is no protocol in place guiding the use of perfusion devices and the decision to use them is hence left to the discretion of the transplant surgeon recovering and/or transplanting the kidney.
For the second aim, the outcome was kidney allograft survival, which was defined as the time elapsed between transplantation and graft failure, either return to dialysis or retransplantation. Death with a functioning graft was taken into account as a competing risk for kidney graft failure. The exposure was high pre-transplant anti-LG3 antibodies, as defined above. The effect modifier was DGF, as defined above. Covariates for all models were selected on the basis of their previously reported associations with DGF or kidney graft survival (20 (link)–22 (link)). These included both recipient and donor characteristics. Recipient variables included age, sex, race, cause of chronic kidney disease (diabetes, vascular/hypertension, autoimmune and other), time on dialysis before transplantation, height and weight, diabetes, history of cardiovascular disease, smoking status (active, past, never smoker), cytomegalovirus serostatus, pre-transplant and peak panel reactive antibodies, previous transplantations, transfusions, pregnancies, induction (basiliximab as the standard protocol, thymoglobulin with or without intravenous immunoglobulins which are reserved for highly sensitized patients), statin and renin-angiotensin system blockers use on admission. Donor variables included age, sex, height and weight, stroke as cause of death, cytomegalovirus serostatus, history of hypertension, diabetes, vascular disease, terminal creatinine, and number of HLA mismatches with the recipient. Recipient age was the only variable with an a priori association with the exposure, anti-LG3 (17 (link)).
For the second aim, the outcome was kidney allograft survival, which was defined as the time elapsed between transplantation and graft failure, either return to dialysis or retransplantation. Death with a functioning graft was taken into account as a competing risk for kidney graft failure. The exposure was high pre-transplant anti-LG3 antibodies, as defined above. The effect modifier was DGF, as defined above. Covariates for all models were selected on the basis of their previously reported associations with DGF or kidney graft survival (20 (link)–22 (link)). These included both recipient and donor characteristics. Recipient variables included age, sex, race, cause of chronic kidney disease (diabetes, vascular/hypertension, autoimmune and other), time on dialysis before transplantation, height and weight, diabetes, history of cardiovascular disease, smoking status (active, past, never smoker), cytomegalovirus serostatus, pre-transplant and peak panel reactive antibodies, previous transplantations, transfusions, pregnancies, induction (basiliximab as the standard protocol, thymoglobulin with or without intravenous immunoglobulins which are reserved for highly sensitized patients), statin and renin-angiotensin system blockers use on admission. Donor variables included age, sex, height and weight, stroke as cause of death, cytomegalovirus serostatus, history of hypertension, diabetes, vascular disease, terminal creatinine, and number of HLA mismatches with the recipient. Recipient age was the only variable with an a priori association with the exposure, anti-LG3 (17 (link)).
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