High PRA is risk factor for death while on kidney transplant wait list

SAN FRANCISCO – Patients awaiting kidney transplantation are more likely to die from any cause and specifically from cardiovascular causes if they have greater immune sensitization as assessed from panel-reactive antibodies, according to a study reported at the annual meeting of the 2014 World Transplant Congress.

"We find PRAs [panel-reactive antibodies] to be a predictor of mortality in wait-listed kidney transplant candidates," commented lead investigator Dr. Ruth Sapir-Pichhadze, a research fellow at the University of Toronto.

©decade3d/thinkstockphotos.com

"When looking at all-cause mortality, our findings support the sliding scale of allocation points by PRA," whereby patients are given higher priority on the waiting list, she added. "When looking at cardiovascular mortality, our findings give rise to a need to conduct further studies to corroborate our findings and investigate the mechanisms by which PRA confers added risk."

In comments provided by e-mail, one of the session’s cochairs, Dr. Jonathan Bromberg of the University of Maryland, Baltimore, said, "The results from this abstract provide a new twist to the analysis of highly sensitized patients, suggesting that a high PRA may be associated with increased cardiovascular and all-cause mortality."

It was difficult to know whether analyses had captured all potential confounders, according to Dr. Bromberg. "Nonetheless, if we take the results at face value, they suggest even more urgency for transplanting this group of patients."

"Since patients with high PRAs already have an advantage on the organ wait list, the answer for these patients lies not in giving them more advantage on the wait list, but rather expanding the living and deceased donor organ supply, and also devising new methods to prevent and treat antibody-mediated rejection, which currently are still inadequate to ensure excellent allograft function in this challenging group of recipients," he concluded.

Dr. Sapir-Pichhadze and her colleagues studied 161,308 adult patients wait-listed for a first kidney transplant between 2000 and 2009 in the Scientific Registry of Transplant Recipients.

The patients had serial measurements of PRAs, which target human leukocyte antigen and are used to assess likely compatibility with donor organs, and were followed until transplantation, death, or end of observation in 2010.

Multivariate analyses showed that when patients having a time-varying PRA of 0% were the reference group, the risk of cardiovascular mortality was elevated for peers with a PRA of 1%-19% (hazard ratio, 1.05), a PRA of 20%-79% (1.11), or a PRA of 80%-100% (1.21), Dr. Sapir-Pichhadze reported at the congress, which was sponsored by the American Society of Transplant Surgeons.

Sensitivity analyses showed that this association was especially pronounced among patients at low risk for comorbidity, defined as those who were under age 40, had been on dialysis less than a year, and did not have coronary artery disease, diabetes, or peripheral vascular disease.

The risk of all-cause mortality was similarly elevated for patients with a PRA of 20%-79% (hazard ratio, 1.11) or a PRA of 80%-100% (1.17). And sensitivity analyses again showed that this association was especially pronounced among the subset at low risk for comorbidity.

Findings were much the same when only baseline PRA was considered, according to Dr. Sapir-Pichhadze, who disclosed no conflicts of interest relevant to the research.

The other session cochair, Dr. Jon Von Visger, of the Ohio State University in Columbus, asked, "Is this association of mortality and higher PRA independent of time on wait list?"

"We addressed this issue, considering how important it is, using two methods," she replied; one was inclusion in models of the time from dialysis initiation to wait listing as a covariate, and the other was performance of a competing risk analysis. And the association persisted in both cases.

A session attendee asked, "Have you looked for a correlation between PRA and C-reactive protein?"

"This is a registry type of analysis, and CRP is not recorded there," Dr. Sapir-Pichhadze replied, while acknowledging that the question is important. "This is where prospective cohort studies potentially would account for this kind of variable, and see if CRP explains similarly [the association that] PRA would otherwise explain."

Dr. Sapir-Pichhadze disclosed no relevant conflicts of interest.

SAN FRANCISCO – Patients awaiting kidney transplantation are more likely to die from any cause and specifically from cardiovascular causes if they have greater immune sensitization as assessed from panel-reactive antibodies, according to a study reported at the annual meeting of the 2014 World Transplant Congress.

"We find PRAs [panel-reactive antibodies] to be a predictor of mortality in wait-listed kidney transplant candidates," commented lead investigator Dr. Ruth Sapir-Pichhadze, a research fellow at the University of Toronto.

©decade3d/thinkstockphotos.com

"When looking at all-cause mortality, our findings support the sliding scale of allocation points by PRA," whereby patients are given higher priority on the waiting list, she added. "When looking at cardiovascular mortality, our findings give rise to a need to conduct further studies to corroborate our findings and investigate the mechanisms by which PRA confers added risk."

In comments provided by e-mail, one of the session’s cochairs, Dr. Jonathan Bromberg of the University of Maryland, Baltimore, said, "The results from this abstract provide a new twist to the analysis of highly sensitized patients, suggesting that a high PRA may be associated with increased cardiovascular and all-cause mortality."

It was difficult to know whether analyses had captured all potential confounders, according to Dr. Bromberg. "Nonetheless, if we take the results at face value, they suggest even more urgency for transplanting this group of patients."

"Since patients with high PRAs already have an advantage on the organ wait list, the answer for these patients lies not in giving them more advantage on the wait list, but rather expanding the living and deceased donor organ supply, and also devising new methods to prevent and treat antibody-mediated rejection, which currently are still inadequate to ensure excellent allograft function in this challenging group of recipients," he concluded.

Dr. Sapir-Pichhadze and her colleagues studied 161,308 adult patients wait-listed for a first kidney transplant between 2000 and 2009 in the Scientific Registry of Transplant Recipients.

The patients had serial measurements of PRAs, which target human leukocyte antigen and are used to assess likely compatibility with donor organs, and were followed until transplantation, death, or end of observation in 2010.

Multivariate analyses showed that when patients having a time-varying PRA of 0% were the reference group, the risk of cardiovascular mortality was elevated for peers with a PRA of 1%-19% (hazard ratio, 1.05), a PRA of 20%-79% (1.11), or a PRA of 80%-100% (1.21), Dr. Sapir-Pichhadze reported at the congress, which was sponsored by the American Society of Transplant Surgeons.

Sensitivity analyses showed that this association was especially pronounced among patients at low risk for comorbidity, defined as those who were under age 40, had been on dialysis less than a year, and did not have coronary artery disease, diabetes, or peripheral vascular disease.

The risk of all-cause mortality was similarly elevated for patients with a PRA of 20%-79% (hazard ratio, 1.11) or a PRA of 80%-100% (1.17). And sensitivity analyses again showed that this association was especially pronounced among the subset at low risk for comorbidity.

Findings were much the same when only baseline PRA was considered, according to Dr. Sapir-Pichhadze, who disclosed no conflicts of interest relevant to the research.

The other session cochair, Dr. Jon Von Visger, of the Ohio State University in Columbus, asked, "Is this association of mortality and higher PRA independent of time on wait list?"

"We addressed this issue, considering how important it is, using two methods," she replied; one was inclusion in models of the time from dialysis initiation to wait listing as a covariate, and the other was performance of a competing risk analysis. And the association persisted in both cases.

A session attendee asked, "Have you looked for a correlation between PRA and C-reactive protein?"

"This is a registry type of analysis, and CRP is not recorded there," Dr. Sapir-Pichhadze replied, while acknowledging that the question is important. "This is where prospective cohort studies potentially would account for this kind of variable, and see if CRP explains similarly [the association that] PRA would otherwise explain."

Dr. Sapir-Pichhadze disclosed no relevant conflicts of interest.

SAN FRANCISCO – Patients awaiting kidney transplantation are more likely to die from any cause and specifically from cardiovascular causes if they have greater immune sensitization as assessed from panel-reactive antibodies, according to a study reported at the annual meeting of the 2014 World Transplant Congress.

"We find PRAs [panel-reactive antibodies] to be a predictor of mortality in wait-listed kidney transplant candidates," commented lead investigator Dr. Ruth Sapir-Pichhadze, a research fellow at the University of Toronto.

©decade3d/thinkstockphotos.com

"When looking at all-cause mortality, our findings support the sliding scale of allocation points by PRA," whereby patients are given higher priority on the waiting list, she added. "When looking at cardiovascular mortality, our findings give rise to a need to conduct further studies to corroborate our findings and investigate the mechanisms by which PRA confers added risk."

In comments provided by e-mail, one of the session’s cochairs, Dr. Jonathan Bromberg of the University of Maryland, Baltimore, said, "The results from this abstract provide a new twist to the analysis of highly sensitized patients, suggesting that a high PRA may be associated with increased cardiovascular and all-cause mortality."

It was difficult to know whether analyses had captured all potential confounders, according to Dr. Bromberg. "Nonetheless, if we take the results at face value, they suggest even more urgency for transplanting this group of patients."

"Since patients with high PRAs already have an advantage on the organ wait list, the answer for these patients lies not in giving them more advantage on the wait list, but rather expanding the living and deceased donor organ supply, and also devising new methods to prevent and treat antibody-mediated rejection, which currently are still inadequate to ensure excellent allograft function in this challenging group of recipients," he concluded.

Dr. Sapir-Pichhadze and her colleagues studied 161,308 adult patients wait-listed for a first kidney transplant between 2000 and 2009 in the Scientific Registry of Transplant Recipients.

The patients had serial measurements of PRAs, which target human leukocyte antigen and are used to assess likely compatibility with donor organs, and were followed until transplantation, death, or end of observation in 2010.

Multivariate analyses showed that when patients having a time-varying PRA of 0% were the reference group, the risk of cardiovascular mortality was elevated for peers with a PRA of 1%-19% (hazard ratio, 1.05), a PRA of 20%-79% (1.11), or a PRA of 80%-100% (1.21), Dr. Sapir-Pichhadze reported at the congress, which was sponsored by the American Society of Transplant Surgeons.

Sensitivity analyses showed that this association was especially pronounced among patients at low risk for comorbidity, defined as those who were under age 40, had been on dialysis less than a year, and did not have coronary artery disease, diabetes, or peripheral vascular disease.

The risk of all-cause mortality was similarly elevated for patients with a PRA of 20%-79% (hazard ratio, 1.11) or a PRA of 80%-100% (1.17). And sensitivity analyses again showed that this association was especially pronounced among the subset at low risk for comorbidity.

Findings were much the same when only baseline PRA was considered, according to Dr. Sapir-Pichhadze, who disclosed no conflicts of interest relevant to the research.

The other session cochair, Dr. Jon Von Visger, of the Ohio State University in Columbus, asked, "Is this association of mortality and higher PRA independent of time on wait list?"

"We addressed this issue, considering how important it is, using two methods," she replied; one was inclusion in models of the time from dialysis initiation to wait listing as a covariate, and the other was performance of a competing risk analysis. And the association persisted in both cases.

A session attendee asked, "Have you looked for a correlation between PRA and C-reactive protein?"

"This is a registry type of analysis, and CRP is not recorded there," Dr. Sapir-Pichhadze replied, while acknowledging that the question is important. "This is where prospective cohort studies potentially would account for this kind of variable, and see if CRP explains similarly [the association that] PRA would otherwise explain."

Dr. Sapir-Pichhadze disclosed no relevant conflicts of interest.