title: Bioartificial kidney alters cytokine response and hemodynamics in endotoxin-challenged uremic animals.
abstract: The mortality from sepsis complicated by renal failure remains extremely high despite the application of modern renal replacement therapy. This study investigated whether treatment with a bioartificial kidney consisting of a hemofilter in a continuous venovenous hemofiltration circuit (CVVH) with a cartridge containing renal proximal tubule cells, also called the Renal Tubule Assist Device (RAD), would alter the course of sepsis in an animal model. The RAD has been previously characterized in vitro and ex vivo and provides transport, metabolic and endocrine activity. Mongrel dogs (n = 10) underwent surgical nephrectomy and 48 h later were treated with CVVH and either a RAD containing cells (n = 5) or an identically prepared sham cartridge (n = 5). After 4 h of therapy, intravenous endotoxin 2 mg/kg was infused over 1 h to simulate gram-negative septic shock. Data on blood pressure, cardiac output and systemic markers of inflammation were collected. Mean peak levels of an anti- inflammatory cytokine, IL-10, were significantly higher in cell-treated animals (15.25 vs. 6.29 ng/ml; p = 0.037), and mean arterial pressures were higher in cell-treated versus sham-treated animals (p < 0.04). We have demonstrated that treatment of an animal model of endotoxin shock and renal failure with a bioartificial kidney has measurable effects on circulating mediators of inflammation and on hemodynamic stability of the challenged animal.
authors.affiliation: Department of Medicine, VA Medical Center and The University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Fissell
authors.forename: D Brad
authors.initials: DB
authors.lastname: Dyke
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
authors.forename: H David
authors.initials: HD
authors.lastname: Humes
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000628:therapy; D000276:Adjuvants, Immunologic / Q000097:blood; D000818:Animals; D001794:Blood Pressure; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D004285:Dogs; D004731:Endotoxins; D006439:Hemodynamics; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D007688:Kidneys, Artificial / Q000592:standards*; D009102:Multiple Organ Failure / Q000097:blood / Q000517:prevention & control; D017582:Renal Replacement Therapy / Q000379:methods; D018805:Sepsis / Q000097:blood / Q000628:therapy; D014511:Uremia / Q000097:blood / Q000628:therapy*
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D004731:Endotoxins; D016753:Interleukin-10