title: Metabolic replacement of kidney function in uremic animals with a bioartificial kidney containing human cells.
abstract: Current renal substitution therapy with hemodialysis or hemofiltration has been an important life-sustaining technology, but it still has suboptimal clinical outcomes in patients with end-stage renal disease or acute renal failure. This therapy replaces the small solute clearance function of the glomerulus but does not replace the metabolic and endocrinologic functions of the tubular cells. This article shows that the combination of a synthetic hemofiltration cartridge and a renal tubule cell assist device (RAD) containing human cells in an extracorporeal circuit replaces filtration, metabolic, and endocrinologic functions in acutely uremic dogs. The RAD maintained excellent performance and durability characteristics for 24 hours of continuous use in the uremic animals. The RAD increased ammonia excretion, glutathione metabolism, and 1,25-dihydroxyvitamin D3 production. Cardiovascular stability in the animals was documented in these studies during this extracorporeal treatment. With these results, clinical evaluation of this device in the treatment of severely ill patients with acute renal failure in an intensive care unit has been initiated.
authors.affiliation: Department of Medicine, VA Medical Center, and University of Michigan, Ann Arbor, MI 48109-0644, USA. dhumes@umich.edu
authors.forename: H David
authors.initials: HD
authors.lastname: Humes
authors.forename: William H
authors.initials: WH
authors.lastname: Fissell
authors.forename: William F
authors.initials: WF
authors.lastname: Weitzel
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Buffington
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Westover
authors.forename: Sherrill M
authors.initials: SM
authors.lastname: MacKay
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Gutierrez
mesh_terms: D058186:Acute Kidney Injury / Q000628:therapy; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002478:Cells, Cultured; D004285:Dogs; D004702:Endocrine Glands / Q000166:cytology / Q000502:physiology; D006440:Hemofiltration / Q000295:instrumentation / Q000379:methods / Q000639:trends; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D007688:Kidneys, Artificial / Q000592:standards / Q000639:trends; D018655:Lymphocyte Count; D017582:Renal Replacement Therapy / Q000295:instrumentation* / Q000379:methods* / Q000639:trends; D013552:Swine; D014511:Uremia / Q000628:therapy*