New approaches expand kidney transplant pool

PALM BEACH, FLA. – Renal transplant surgeons are using novel methods to expand the pool of donor organs: Using kidneys from donors with acute kidney injury, and vetting and improving the function of kidneys by applying pulsatile machine perfusion to stored kidneys pending transplant.

These approaches can overlap, as machine perfusion has become an important tool for improving the function of kidneys from donors with acute kidney injury (AKI) as well as other marginal kidneys such as those from extended-criteria donors and donation after cardiac death.

Surgeons at Wake Forest University, Winston-Salem, N.C., began transplanting kidneys from AKI donors in 2007, and by mid-2012 they had placed 84 of these organs, resulting in actuarial 5-year patient-survival and graft-survival rates that matched transplants during the same period with kidneys from non-AKI donors, Dr. Alan C. Farney said at the annual meeting of the Southern Surgical Association.

Seventy-four of these kidneys (88%) underwent machine perfusion, for a minimum of 6 hours and more often overnight, said Dr. Farney’s colleague, Dr. Robert J. Stratta, professor of surgery at Wake Forest. "We try to pump whenever possible, and in a perfect world we’d like to see all kidneys pumped" before they are transplanted, Dr. Stratta said. In addition to improving function, mechanical perfusion allows surgeons to assess kidney function. If resistance in the kidney is more than 0.4 or 0.5 mm Hg/mL per minute, "we tend to discard it," he noted.

A second report at the meeting further documented the ability of mechanical perfusion to boost kidney function. In a review of more than 50,000 adult, isolated kidney transplants done on American patients during January 2005–March 2011, machine perfusion prior to transplant led to an average 8-percentage-point cut in the rate of delayed kidney function in a pair of analyses that accounted for baseline patient differences. This means that every 13 kidneys treated before transplant with mechanical perfusion prevented a case of delayed graft function (DGF) following transplantation, resulting in fewer patients requiring hemodialysis, Dr. Glen A. Franklin reported at the meeting.

Prevention of DGF mitigates edema, reduces the need for wound drainage, and decreases the risk for infection, factors that – along with the need for dialysis – drive up costs. Preventing these complications and their associated costs potentially offsets the extra expense of routinely perfusing each kidney before transplantation, Dr. Stratta said.

Dr. Stratta and his associates reviewed the outcomes of 84 transplants of kidneys from donors with AKI done at Wake Forest since 2007 and compared this against the outcomes of 283 concurrent kidney transplants performed during the same 2007-2012 period using organs from donors without AKI. A major, statistically significant difference in protocol for the two types of organs was that 88% of the AKI-derived kidneys underwent machine perfusion before transplant, compared with 51% of the kidneys that came from non-AKI donors, reported Dr. Farney, professor of surgery at Wake Forest.

A major difference in outcomes was that the incidence of DGF following transplantation occurred in 41% of patients who received a kidney from an AKI donor, compared with a 27% DGF rate among patients whose kidneys came from non-AKI donors, a statistically-significant difference.

Despite this, actuarial 5-year patient survival was 98% among the AKI kidney recipients and 90% among the non-AKI kidney recipients. Five-year graft survival was 78% in the AKI-kidney recipients and 71% in patients who received a non-AKI organ. The between-group differences were not statistically significant, Dr. Farney said.

The data also showed an unexpected difference in the way that DGF appeared to affect graft survival. Among patients whose kidneys came from non-AKI donors, the 5-year graft survival rate was 90% among the 206 patients who did not have DGF, but fell to 68% among the 77 patients in this group who had DGF, a statistically-significant difference. In contrast, among patients who received kidneys from AKI donors, the incidence of DGF had no significant impact on long-term graft survival.

The data also showed that the severity of AKI had no significant impact on graft survival. Donors with terminal estimated glomerular filtration rates of 10-20 mL/min per 1.73 m² had graft survival rates similar to those of patients who received kidneys from AKI donors with terminal estimated glomerular filtration rates above 30 mL/min per 1.73².

Overall, the results suggest that "using kidneys from AKI donors is a safe method to significantly expand the donor pool for kidney transplantation," Dr. Farney concluded.

"I’m impressed with how, for several years, the Wake Forest group has used kidneys that others may have discarded. The outcomes they report are quite encouraging," commented Dr. Douglas P. Slakey, professor and chairman of surgery at Tulane Medical Center, New Orleans.

The impact that machine perfusion of kidneys can have on DGF before transplantation was examined in a much larger data set by Dr. Franklin and his associates at the University of Louisville (Ky.). They reviewed data collected by the United Network for Organ Sharing on 52,052 isolated, adult U.S. kidney transplants during January 2005–March 2011. The series included 19,372 kidneys (37%) that underwent machine perfusion before transplant.

A propensity-score analysis that compared 13,293 organ recipients who received perfused kidneys with 13,293 recipients who received nonperfused kidneys and matched by a variety of donor and recipient characteristics showed that the incidence of DGF during the first week following transplantation was 21% among the perfused organ recipients. The incidence among patients who received a nonperfused kidney was 29%, a statistically significant difference, said Dr. Franklin, a professor of surgery at the University of Louisville.

A second analysis focused on pairs of kidneys that came from 2,290 donors where one kidney underwent perfusion and the other did not. After adjustment for recipient differences, the incidence of DGF was 20% in recipients who received a perfused kidney and 28% in those who received a nonperfused kidney, again an 8% difference that was statistically significant.

The cost of machine perfusion of a kidney varies from region to region, but at Louisville runs about $1,000 to $2,000 per organ, said Dr. Robert M. Cannon, a surgeon at the University of Louisville and a collaborator on the study. "I think you can justify this cost based on the decrease in DGF," and because it allows scheduling of transplants during usual operating-room hours, eliminating the need for emergency transplant surgery in the middle of the night, Dr. Cannon said in an interview.

Several hours of machine perfusion also likely improves kidney function, he noted. "With cold storage, kidneys undergo intense vasospasm that damages the organ. Machine perfusion alleviates that to an extent, and gets more preservation fluid into the organ."

Dr. Farney, Dr. Stratta, Dr. Franklin, and Dr. Cannon, and Dr. Slakey had no disclosures to report.

m.zoler@elsevier.com

On Twitter @mitchelzoler

PALM BEACH, FLA. – Renal transplant surgeons are using novel methods to expand the pool of donor organs: Using kidneys from donors with acute kidney injury, and vetting and improving the function of kidneys by applying pulsatile machine perfusion to stored kidneys pending transplant.

These approaches can overlap, as machine perfusion has become an important tool for improving the function of kidneys from donors with acute kidney injury (AKI) as well as other marginal kidneys such as those from extended-criteria donors and donation after cardiac death.

Surgeons at Wake Forest University, Winston-Salem, N.C., began transplanting kidneys from AKI donors in 2007, and by mid-2012 they had placed 84 of these organs, resulting in actuarial 5-year patient-survival and graft-survival rates that matched transplants during the same period with kidneys from non-AKI donors, Dr. Alan C. Farney said at the annual meeting of the Southern Surgical Association.

Seventy-four of these kidneys (88%) underwent machine perfusion, for a minimum of 6 hours and more often overnight, said Dr. Farney’s colleague, Dr. Robert J. Stratta, professor of surgery at Wake Forest. "We try to pump whenever possible, and in a perfect world we’d like to see all kidneys pumped" before they are transplanted, Dr. Stratta said. In addition to improving function, mechanical perfusion allows surgeons to assess kidney function. If resistance in the kidney is more than 0.4 or 0.5 mm Hg/mL per minute, "we tend to discard it," he noted.

A second report at the meeting further documented the ability of mechanical perfusion to boost kidney function. In a review of more than 50,000 adult, isolated kidney transplants done on American patients during January 2005–March 2011, machine perfusion prior to transplant led to an average 8-percentage-point cut in the rate of delayed kidney function in a pair of analyses that accounted for baseline patient differences. This means that every 13 kidneys treated before transplant with mechanical perfusion prevented a case of delayed graft function (DGF) following transplantation, resulting in fewer patients requiring hemodialysis, Dr. Glen A. Franklin reported at the meeting.

Prevention of DGF mitigates edema, reduces the need for wound drainage, and decreases the risk for infection, factors that – along with the need for dialysis – drive up costs. Preventing these complications and their associated costs potentially offsets the extra expense of routinely perfusing each kidney before transplantation, Dr. Stratta said.

Dr. Stratta and his associates reviewed the outcomes of 84 transplants of kidneys from donors with AKI done at Wake Forest since 2007 and compared this against the outcomes of 283 concurrent kidney transplants performed during the same 2007-2012 period using organs from donors without AKI. A major, statistically significant difference in protocol for the two types of organs was that 88% of the AKI-derived kidneys underwent machine perfusion before transplant, compared with 51% of the kidneys that came from non-AKI donors, reported Dr. Farney, professor of surgery at Wake Forest.

A major difference in outcomes was that the incidence of DGF following transplantation occurred in 41% of patients who received a kidney from an AKI donor, compared with a 27% DGF rate among patients whose kidneys came from non-AKI donors, a statistically-significant difference.

Despite this, actuarial 5-year patient survival was 98% among the AKI kidney recipients and 90% among the non-AKI kidney recipients. Five-year graft survival was 78% in the AKI-kidney recipients and 71% in patients who received a non-AKI organ. The between-group differences were not statistically significant, Dr. Farney said.

The data also showed an unexpected difference in the way that DGF appeared to affect graft survival. Among patients whose kidneys came from non-AKI donors, the 5-year graft survival rate was 90% among the 206 patients who did not have DGF, but fell to 68% among the 77 patients in this group who had DGF, a statistically-significant difference. In contrast, among patients who received kidneys from AKI donors, the incidence of DGF had no significant impact on long-term graft survival.

The data also showed that the severity of AKI had no significant impact on graft survival. Donors with terminal estimated glomerular filtration rates of 10-20 mL/min per 1.73 m² had graft survival rates similar to those of patients who received kidneys from AKI donors with terminal estimated glomerular filtration rates above 30 mL/min per 1.73².

Overall, the results suggest that "using kidneys from AKI donors is a safe method to significantly expand the donor pool for kidney transplantation," Dr. Farney concluded.

"I’m impressed with how, for several years, the Wake Forest group has used kidneys that others may have discarded. The outcomes they report are quite encouraging," commented Dr. Douglas P. Slakey, professor and chairman of surgery at Tulane Medical Center, New Orleans.

The impact that machine perfusion of kidneys can have on DGF before transplantation was examined in a much larger data set by Dr. Franklin and his associates at the University of Louisville (Ky.). They reviewed data collected by the United Network for Organ Sharing on 52,052 isolated, adult U.S. kidney transplants during January 2005–March 2011. The series included 19,372 kidneys (37%) that underwent machine perfusion before transplant.

A propensity-score analysis that compared 13,293 organ recipients who received perfused kidneys with 13,293 recipients who received nonperfused kidneys and matched by a variety of donor and recipient characteristics showed that the incidence of DGF during the first week following transplantation was 21% among the perfused organ recipients. The incidence among patients who received a nonperfused kidney was 29%, a statistically significant difference, said Dr. Franklin, a professor of surgery at the University of Louisville.

A second analysis focused on pairs of kidneys that came from 2,290 donors where one kidney underwent perfusion and the other did not. After adjustment for recipient differences, the incidence of DGF was 20% in recipients who received a perfused kidney and 28% in those who received a nonperfused kidney, again an 8% difference that was statistically significant.

The cost of machine perfusion of a kidney varies from region to region, but at Louisville runs about $1,000 to $2,000 per organ, said Dr. Robert M. Cannon, a surgeon at the University of Louisville and a collaborator on the study. "I think you can justify this cost based on the decrease in DGF," and because it allows scheduling of transplants during usual operating-room hours, eliminating the need for emergency transplant surgery in the middle of the night, Dr. Cannon said in an interview.

Several hours of machine perfusion also likely improves kidney function, he noted. "With cold storage, kidneys undergo intense vasospasm that damages the organ. Machine perfusion alleviates that to an extent, and gets more preservation fluid into the organ."

Dr. Farney, Dr. Stratta, Dr. Franklin, and Dr. Cannon, and Dr. Slakey had no disclosures to report.

m.zoler@elsevier.com

On Twitter @mitchelzoler

PALM BEACH, FLA. – Renal transplant surgeons are using novel methods to expand the pool of donor organs: Using kidneys from donors with acute kidney injury, and vetting and improving the function of kidneys by applying pulsatile machine perfusion to stored kidneys pending transplant.

These approaches can overlap, as machine perfusion has become an important tool for improving the function of kidneys from donors with acute kidney injury (AKI) as well as other marginal kidneys such as those from extended-criteria donors and donation after cardiac death.

Surgeons at Wake Forest University, Winston-Salem, N.C., began transplanting kidneys from AKI donors in 2007, and by mid-2012 they had placed 84 of these organs, resulting in actuarial 5-year patient-survival and graft-survival rates that matched transplants during the same period with kidneys from non-AKI donors, Dr. Alan C. Farney said at the annual meeting of the Southern Surgical Association.

Seventy-four of these kidneys (88%) underwent machine perfusion, for a minimum of 6 hours and more often overnight, said Dr. Farney’s colleague, Dr. Robert J. Stratta, professor of surgery at Wake Forest. "We try to pump whenever possible, and in a perfect world we’d like to see all kidneys pumped" before they are transplanted, Dr. Stratta said. In addition to improving function, mechanical perfusion allows surgeons to assess kidney function. If resistance in the kidney is more than 0.4 or 0.5 mm Hg/mL per minute, "we tend to discard it," he noted.

A second report at the meeting further documented the ability of mechanical perfusion to boost kidney function. In a review of more than 50,000 adult, isolated kidney transplants done on American patients during January 2005–March 2011, machine perfusion prior to transplant led to an average 8-percentage-point cut in the rate of delayed kidney function in a pair of analyses that accounted for baseline patient differences. This means that every 13 kidneys treated before transplant with mechanical perfusion prevented a case of delayed graft function (DGF) following transplantation, resulting in fewer patients requiring hemodialysis, Dr. Glen A. Franklin reported at the meeting.

Prevention of DGF mitigates edema, reduces the need for wound drainage, and decreases the risk for infection, factors that – along with the need for dialysis – drive up costs. Preventing these complications and their associated costs potentially offsets the extra expense of routinely perfusing each kidney before transplantation, Dr. Stratta said.

Dr. Stratta and his associates reviewed the outcomes of 84 transplants of kidneys from donors with AKI done at Wake Forest since 2007 and compared this against the outcomes of 283 concurrent kidney transplants performed during the same 2007-2012 period using organs from donors without AKI. A major, statistically significant difference in protocol for the two types of organs was that 88% of the AKI-derived kidneys underwent machine perfusion before transplant, compared with 51% of the kidneys that came from non-AKI donors, reported Dr. Farney, professor of surgery at Wake Forest.

A major difference in outcomes was that the incidence of DGF following transplantation occurred in 41% of patients who received a kidney from an AKI donor, compared with a 27% DGF rate among patients whose kidneys came from non-AKI donors, a statistically-significant difference.

Despite this, actuarial 5-year patient survival was 98% among the AKI kidney recipients and 90% among the non-AKI kidney recipients. Five-year graft survival was 78% in the AKI-kidney recipients and 71% in patients who received a non-AKI organ. The between-group differences were not statistically significant, Dr. Farney said.

The data also showed an unexpected difference in the way that DGF appeared to affect graft survival. Among patients whose kidneys came from non-AKI donors, the 5-year graft survival rate was 90% among the 206 patients who did not have DGF, but fell to 68% among the 77 patients in this group who had DGF, a statistically-significant difference. In contrast, among patients who received kidneys from AKI donors, the incidence of DGF had no significant impact on long-term graft survival.

The data also showed that the severity of AKI had no significant impact on graft survival. Donors with terminal estimated glomerular filtration rates of 10-20 mL/min per 1.73 m² had graft survival rates similar to those of patients who received kidneys from AKI donors with terminal estimated glomerular filtration rates above 30 mL/min per 1.73².

Overall, the results suggest that "using kidneys from AKI donors is a safe method to significantly expand the donor pool for kidney transplantation," Dr. Farney concluded.

"I’m impressed with how, for several years, the Wake Forest group has used kidneys that others may have discarded. The outcomes they report are quite encouraging," commented Dr. Douglas P. Slakey, professor and chairman of surgery at Tulane Medical Center, New Orleans.

The impact that machine perfusion of kidneys can have on DGF before transplantation was examined in a much larger data set by Dr. Franklin and his associates at the University of Louisville (Ky.). They reviewed data collected by the United Network for Organ Sharing on 52,052 isolated, adult U.S. kidney transplants during January 2005–March 2011. The series included 19,372 kidneys (37%) that underwent machine perfusion before transplant.

A propensity-score analysis that compared 13,293 organ recipients who received perfused kidneys with 13,293 recipients who received nonperfused kidneys and matched by a variety of donor and recipient characteristics showed that the incidence of DGF during the first week following transplantation was 21% among the perfused organ recipients. The incidence among patients who received a nonperfused kidney was 29%, a statistically significant difference, said Dr. Franklin, a professor of surgery at the University of Louisville.

A second analysis focused on pairs of kidneys that came from 2,290 donors where one kidney underwent perfusion and the other did not. After adjustment for recipient differences, the incidence of DGF was 20% in recipients who received a perfused kidney and 28% in those who received a nonperfused kidney, again an 8% difference that was statistically significant.

The cost of machine perfusion of a kidney varies from region to region, but at Louisville runs about $1,000 to $2,000 per organ, said Dr. Robert M. Cannon, a surgeon at the University of Louisville and a collaborator on the study. "I think you can justify this cost based on the decrease in DGF," and because it allows scheduling of transplants during usual operating-room hours, eliminating the need for emergency transplant surgery in the middle of the night, Dr. Cannon said in an interview.

Several hours of machine perfusion also likely improves kidney function, he noted. "With cold storage, kidneys undergo intense vasospasm that damages the organ. Machine perfusion alleviates that to an extent, and gets more preservation fluid into the organ."

Dr. Farney, Dr. Stratta, Dr. Franklin, and Dr. Cannon, and Dr. Slakey had no disclosures to report.

m.zoler@elsevier.com

On Twitter @mitchelzoler