VANCOUVER, British Columbia—Findings from two large studies presented at The Transplantation Congress in Vancouver provide new insights into the practice of matching donors and recipients by age and point to ways to expand the options for improving kidney and patient survival among recipients of all ages.
In one study, researchers analyzed data from the United Network for Organ Sharing (UNOS) involving more than 108,188 deceased-donor kidney transplants between 1995 and 2008. The transplants included in the analysis only involved deceased donors over age 10 and adult recipients. The results are scheduled for publication in the Archives of Surgery.
Acute rejection rates rise with increasing donor age but decrease with increasing recipient age, data show. Furthermore, older grafts transplanted into older recipients are associated with a lower rate of acute rejection and of risks for graft loss. Overall, the investigators determined, death-censored graft survival increases with increasing recipient age, from a 42% 10-year survival rate among recipients aged 18-29 to a 67% 10-year survival rate among recipients over 70 years old.
The investigators posit that increasing graft survival with age can be explained by the muted immune response of older recipients. Consequently, they believe immunosuppression will need to be age-adapted.
“Building on these findings, we are currently studying the correlation of immune response and age in animal models,” said lead investigator Stefan G. Tullius, MD, PhD, Chief, Division of Transplant Surgery, Brigham and Women’s Hospital, and Associate Professor of Surgery at Harvard Medical School. “This is producing very exciting data that may allow us in the future to understand the immune response in general in a better way, to refine immunosuppression, and hence possibly help further optimize organ allocation in the future.”
The other study involved deceased-donor kidney transplants performed between 2006 and 2008. Data showed that, contrary to popular belief, allograft lifespan depends more on donor age than recipient age. Conversely, the investigators also found that recipient lifespan is more dependent on recipient age than donor age, with the lifespan in recipients older than 60 holding steady at approximately 10 years across the spectrum of donor ages.
“Beyond the belief that kidneys with very long potential lifespans should not be allocated to candidates with very short potential lifespans, I am personally not that much of an enthusiast for donor and recipient age-matching,” said lead investigator Alan Leichtman, MD, Associate Professor of Nephrology at the University of Michigan in Ann Arbor. “Previous theories seeking to explain the relationship between donor chronological age and transplant survival solely on the basis of preexisting donor disease, from biopsy findings, and hyperfiltration are likely overly simplistic and fail to recognize renal senescence as an active and potentially interventionable process.”
He said he believes gene- and tissue-engineering therapies will be developed in the future that will reduce the biological aging of the kidneys and hence improve graft survival.
Stuart Flechner, MD, who was a co-moderator of the TTC session at which Drs. Tullius and Leichtman presented their findings, said these studies are robust and help to further illuminate the complexities of kidney allocation based on age.
Some researchers, including himself, have argued that donor age is a surrogate for nephron dose or glomerular filtration rate, and that recipient age is a surrogate for cardiovascular disease. “These are perhaps the two major risk factors affecting outcomes beyond five years,” said Dr. Flechner, Professor of Surgery at the Cleveland Clinic Lerner College of Medicine and Director of Clinical Research in the Section of Renal Transplantation, Transplant Center/Glickman Urological and Kidney Institute, Cleveland Clinic Foundation. “However, we all know there are people under 40 with severe cardiac disease and people over 60 in the Transplant Olympics. The best use of kidneys is a work in progress and these reports add an important piece to this puzzle.”