May 16, 2022

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 1 in 3 people.                                                        

Sometimes finding a perfect match for a kidney can turn into an endless search – with blood, tissue, and antibody compatibility needed between donor and recipient. A study recently published in the journal Transplantation shows researchers may be able to help increase the number of kidney transplants thanks to a new transplant procedure working between mismatched donors and recipients. 

Rhesus monkeys at the Wisconsin National Primate Research Center are playing a starring role in a study to improve the success of kidney transplants. Animal care experts and pathologists 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 complement activation, implicated in delayed graft function. They used a high-dose complement blockade therapy called C1INH (or rhC1INH in rhesus monkeys) to discover it worked well in preventing delayed graft function and antibody-mediated kidney rejection. Furthermore, the researchers used donor kidneys from deceased animals to make up for the lack of available deceased human kidney donors (approximately 20% of human donor kidneys are discarded due to the length of storage time or 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 difficulties. The other seven animals in the treatment group underwent 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 transplant outcomes.

The research team thanks the veterinary and SPI staff at the Wisconsin National Primate Research Center for their “extraordinary care for the animals during the observation period.”

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