BACKGROUND:Posttransplantation acute renal failure (ARF) occurs in roughly 25% of recipients of organs from deceased donors. Inflammation in the donor organ is associated with risk for ARF. OBJECTIVE: To determine whether administering corticosteroids to deceased organ donors reduces the incidence and duration of ARF in organ recipients more than placebo. DESIGN: Parallel, blocked randomized trial, performed between February 2006 and November 2008, with computer-generated randomization and centralized allocation. Investigators were masked to group assignment. (Controlled-trials.com registration number: ISRCTN78828338) SETTING: 3 renal transplantation centers in Austria and Hungary. PATIENTS: 306 deceased heart-beating donors and 455 renal transplant recipients. INTERVENTIONS: Organ donors were administered an intravenous infusion of either 1000 mg of methylprednisolone (136 donors) or placebo (0.9% saline) (133 donors) at least 3 hours before organ harvesting. MEASUREMENTS: Incidence of ARF, defined as more than 1 dialysis session in the first week after transplantation, was the primary end point. Secondary and other end points included duration of ARF and trajectories of serum creatinine level. The suppression of immune response and inflammation by the intervention was assessed in the donor organ on a genome-wide basis. RESULTS: 52 of 238 recipients (22%) of kidneys from steroid-treated donors and 54 of 217 recipients (25%) of kidneys from placebo-treated donors had ARF (difference, 3 percentage points [95% CI, -11 to 5 percentage points]). One graft was lost on day 1 in each group, and 1 recipient in the placebo group died of cardiac arrest on day 2. The median duration of ARF was 5 days (interquartile range, 2 days) in the steroid group and 4 days (interquartile range, 2 days) in the placebo group (P = 0.31). The groups had similar trajectories of serum creatinine level in the first week (P = 0.72). Genomic analysis showed suppressed inflammation and immune response in kidney biopsies from deceased donors who received corticosteroids. LIMITATION: Donors and recipients were mainly white, and all were from 3 transplantation centers in central Europe, which may limit generalizability. CONCLUSION: Systemic suppression of inflammation in deceased donors by corticosteroids did not reduce the incidence or duration of posttransplantation ARF in allograft recipients. PRIMARY FUNDING SOURCE: Austrian Science Fund and Austrian Academy of Science.
RCT Entities:
BACKGROUND: Posttransplantation acute renal failure (ARF) occurs in roughly 25% of recipients of organs from deceased donors. Inflammation in the donor organ is associated with risk for ARF. OBJECTIVE: To determine whether administering corticosteroids to deceased organ donors reduces the incidence and duration of ARF in organ recipients more than placebo. DESIGN: Parallel, blocked randomized trial, performed between February 2006 and November 2008, with computer-generated randomization and centralized allocation. Investigators were masked to group assignment. (Controlled-trials.com registration number: ISRCTN78828338) SETTING: 3 renal transplantation centers in Austria and Hungary. PATIENTS: 306 deceased heart-beating donors and 455 renal transplant recipients. INTERVENTIONS: Organ donors were administered an intravenous infusion of either 1000 mg of methylprednisolone (136 donors) or placebo (0.9% saline) (133 donors) at least 3 hours before organ harvesting. MEASUREMENTS: Incidence of ARF, defined as more than 1 dialysis session in the first week after transplantation, was the primary end point. Secondary and other end points included duration of ARF and trajectories of serum creatinine level. The suppression of immune response and inflammation by the intervention was assessed in the donor organ on a genome-wide basis. RESULTS: 52 of 238 recipients (22%) of kidneys from steroid-treated donors and 54 of 217 recipients (25%) of kidneys from placebo-treated donors had ARF (difference, 3 percentage points [95% CI, -11 to 5 percentage points]). One graft was lost on day 1 in each group, and 1 recipient in the placebo group died of cardiac arrest on day 2. The median duration of ARF was 5 days (interquartile range, 2 days) in the steroid group and 4 days (interquartile range, 2 days) in the placebo group (P = 0.31). The groups had similar trajectories of serum creatinine level in the first week (P = 0.72). Genomic analysis showed suppressed inflammation and immune response in kidney biopsies from deceased donors who received corticosteroids. LIMITATION: Donors and recipients were mainly white, and all were from 3 transplantation centers in central Europe, which may limit generalizability. CONCLUSION: Systemic suppression of inflammation in deceased donors by corticosteroids did not reduce the incidence or duration of posttransplantation ARF in allograft recipients. PRIMARY FUNDING SOURCE: Austrian Science Fund and Austrian Academy of Science.
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