March 16, 2022
By Jordana Lenon
Rhesus monkeys at the Wisconsin National Primate Research Center have played a starring role in a study aimed at improving the success of kidney transplants.
About 24,000 kidney transplants are performed in the US each year, yet more than 90,000 people are waiting for a transplant. Even when patients get a transplanted kidney, organ rejection is a common complication in the first year after a transplant, affecting up to 1 in 3 people.
Most people are not only waiting for a kidney, but for one that’s a perfect match – with blood, tissue and antibody compatibility between donor and recipient. But researchers may be able to help increase the number of kidney transplants thanks to a new transplant procedure that works between mismatched donors and recipients. The study was published in the journal Transplantation.
Animal care experts and pathologists at the Wisconsin National Primate Research Center worked with transplant surgeon Luis Fernandez and other researchers to test the new procedure. Fernandez directed the University of Wisconsin Hospital and Clinics liver transplant program until last year and is now a transplant division chief at Loyola Medicine in Chicago. Also on the research team were preclinical and clinical experts from the University of Wisconsin–Madison School of Medicine and Public Health, Texas Southwest Medical Center, Pharming Technologies BV in Leiden, The Netherlands, and Leiden University Medical Center.
The researchers focused on a process called complement activation, which is implicated in delayed graft function. They used a high-dose complement blockade therapy called C1INH (or rhC1INH in rhesus monkeys) and discovered that it worked well in preventing delayed graft function and antibody-mediated kidney rejection. Furthermore, the researchers used donor kidneys from deceased animals in this study, because there is such great demand for human kidneys that deceased human donors are also used. But about 20 percent of human kidneys from deceased organ donors end up being discarded, due to the length of storage time and often advanced donor age.
Of all the mismatched kidney transplant recipients, four out of five monkeys treated with a saline control developed delayed graft function complications, whereas only one in eight rhC1INH-treated recipients experienced complications. The other seven animals in the treatment group experienced successful transplants with fully functioning kidneys. The study results support high-dose C1INH complement blockade therapy in mismatched transplant recipients as an effective strategy to reduce kidney injury and inflammation, prevent delayed graft function, delay antibody-mediated rejection development, and improve overall transplant outcomes.
In the journal article, the research team also thanked the veterinary and SPI staff at the Wisconsin National Primate Research Center for their “extraordinary care for the animals during the observation period.”