St. Louis, June 24, 1998 -- Researchers at Washington University School of Medicine in St. Louis have found a novel way to grow new kidneys that may one day lessen the need for human donor organs. When they placed a developing rat kidney inside the abdominal cavity of an adult rat, it became a smaller version of an adult kidney.
"The organs look just like normal rat kidneys," says lead scientist Marc R. Hammerman, M.D., the Chromalloy Professor of Renal Diseases in Medicine and director of the Renal Division. Hammerman notes that their function needs to be improved before they can be of use, but he hopes the work could be used to develop transplantable kidneys that would be less likely to be rejected." More than 39,000 kidney patients currently are on the national waiting list of the United Network for Organ Sharing. In 1997, 2,000 people died waiting for a kidney.
Hammerman's results are published in the July issue of Kidney International. His wife, Nancy Hammerman, is a co-author. An art teacher in the Pattonville School District, Nancy Hammerman suggested that developing kidneys might be a source of transplants after hearing her husband give a transplant lecture in March 1996 in London, England.
Soon after, Hammerman and research instructor Sharon Rogers tried placing single developing kidneys under the capsule that covers the kidney of adult rats. The juvenile kidneys, as small as a pencil tip, are called metanephroi. They survived and grew "despite concern that the rats' immune defenses would attack the foreign organs." "They actually grew and developed into kidneys that you don't need to immunosuppress," Hammerman says.
The kidneys did not grow well, possibly due to tight quarters inside the kidney capsule. But when the researchers placed the dots of kidney tissue inside a sac-like membrane that surrounds and supports abdominal organs, they reached a third of the size of an adult kidney within 6 weeks. The membrane releases growth promoting factors and ones that stimulate blood vessel formation.
Within four weeks, the rats had produced new blood vessels that connected the kidneys to their own blood supply, creating chimeric kidneys containing parts from two different animals. To test whether the organs function, Hammerman and Rogers removed a kidney from several animals and attached each foreign kidney to the ureter left behind. The ureter is a tube at the base of a kidney that carries urine to the bladder.
The researchers removed the rats' other kidneys at this point and tested the chimeras' ability to single-handedly carry out kidney function. A small amount of a sugar called inulin was injected into the rats' bloodstream. It was cleared by the chimeric kidneys and dumped into the rat's urine.
The chimeric kidneys had less than 1 percent of a normal kidney's function. In comparison, a dialysis machine augments a person's kidney function by roughly 10 percent. The researchers are testing a cocktail of growth factors to try to increase chimera function to 20 percent of normal. "We're not at the point where these kidneys can sustain life, but we're working on it," Hammerman says.
They also have shown that chimeric kidneys thrive and are not rejected by rats' immune systems within 6 months of attachment to ureters. Hammerman suspects this partly reflects the host origin of the kidney's blood vessels because foreign blood vessels are a major stimulator of rejection. The use of a developing kidney also was key to reducing the immune response. A rat rejects an adult kidney from another rat within a week. "A rat kidney is sufficiently different from a human kidney to be a poor transplant choice, but pig kidneys are similar in size and function to those of humans. Hammerman suggests that developing pig kidneys might be more suitable for transplantation. Once a kidney was transplanted, it would be fed by blood vessels from the human host. " He notes, however, that the risk of transmitting viruses from pigs to humans needs to be adequately addressed before considering such transplants. "This work is only a first step," he emphasizes. "We're a long way from be ing able to use this technology in humans."
The full- and part-time faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC Health System.
Rogers SA, Lowell JA, Hammerman NA, Hammerman MR (1998). Transplantation of developing metanephroi into adult rats. Kidney International, 54, 27-37.
This work was supported by grants from the National Institutes of Health.
Journal
Kidney International