Circulating donor-specific anti-HLA antibody (DSA) and longer cold ischemia time independently predict worse long-term transplantation outcomes among recipients of expanded criteria donor (ECD) kidneys, according to French investigators.

In a large, prospective study, a team led by Alexandre Loupy, MD, of the Paris Translational Research Centre for Organ Transplantation, Paris Descartes University, found that, compared with ECD kidney recipients who did not have circulating DSA on the day of transplantation (ECD/DSA-), recipients who did (ECD/DSA+) had significantly lower graft survival rates at 7 years (44% vs. 85%). Antibody mediated rejection was the main cause of graft loss in the ECD kidney recipients with circulating DSA, the researchers reported online in the British Medical Journal.

ECD/DSA+ recipients had a significant 4.4-fold increased risk of graft loss compared with ECD/DSA- recipients and a 5.6-fold increased risk of graft loss compared with all other transplant therapies.

ECD/DSA- recipients experienced a 41% improvement in graft survival at 7 years compared with ECD-DSA+ recipients, according to the investigators.

When the researchers performed a Cox analysis in the ECD kidney group, they found that a cold ischemia time of 12–24 hours and 24 hours or longer were associated with a significant 2.49 and 3.77-fold increased risk of graft loss, respectively, compared with a cold ischemia time of less than 12 hours.

The researchers concluded that circulating DSA and cold ischemia time are the main independent determinants of outcome from ECD kidney transplantation.

“Although circulating DSA is known to impair allograft outcomes, its specific impact, the amplitude of its effect, and its independence from other relevant predictors have not been addressed in the ECD population,” Dr. Loupy told Renal & Urology News. “Our data suggest that ECD kidneys may be particularly vulnerable to the effect of DSA injury and cold ischemia time.”

The study's principal cohort included 2,763 kidney recipients; of these, 916 received ECD kidneys and 1,847 received kidneys from standard criteria donors (SCD). The median follow-up time after transplantation for the overall cohort was 5.54 years, but was shorter for ECD kidney recipients than SCD kidney recipients (5.24 vs. 5.72 years).

ECD allograft survival at 7 years improved significantly with screening and transplantation in the absence of circulated DSA and with cold ischemia times of less than 12 hours.

“Our results support the implementation of active ECD specific allocation policies for avoiding DSA, decreasing cold ischaemia time, and performing adequate recipient matching,” the authors concluded. “In the present study, exclusive allocation of ECD kidneys to patients without circulating DSA would have translated to a 544.6 allograft life years saved during the nine years of study inclusion time.”

As a result of study findings, Dr. Loupy said his practice plans to allocate ECD kidneys exclusively to recipients without circulating anti-HLA DSA and expand the indications for using machine perfusion for ECD kidneys due to the deleterious effect of prolonged cold ischemia time.

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