RESUMEN
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.
Asunto(s)
Túbulos Renales Proximales/fisiología , Riñones Artificiales , Terapia de Reemplazo Renal/instrumentación , Terapia de Reemplazo Renal/métodos , Uremia/terapia , Lesión Renal Aguda/terapia , Animales , Transporte Biológico/fisiología , Células Cultivadas , Perros , Glándulas Endocrinas/citología , Glándulas Endocrinas/fisiología , Hemofiltración/instrumentación , Hemofiltración/métodos , Hemofiltración/tendencias , Humanos , Túbulos Renales Proximales/citología , Túbulos Renales Proximales/metabolismo , Riñones Artificiales/normas , Riñones Artificiales/tendencias , Recuento de Linfocitos , Terapia de Reemplazo Renal/tendencias , PorcinosRESUMEN
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.