Effect Of Bioartificial Renal Tubule Constructed With Human Renal Cells On Porcine Model With Multiple Organ Dysfunction Syndromes And Acute Renal Failure

Background and Purpose Renal replacement therapy plays a very important role in the treatment of acute renal failure (ARF). But patients with ARF complicated with multiple organ dysfunction syndromes (MODS) still have mortality rates of 60-100% despite the application ofconventional continuous renal replacement therapy (CRRT). Poor outcomes may be due to the fact that these therapies substitute for the glomeruli filtrate function only, but do not replace the metabolic, reclamation, and endocrine function of renal tubule in vitro. Humes HD first reported the establishment of bioartificial renal tubule assist device in vitro in 1997.In 2000 we first constructed the RAD using LLC-PK1 cells in China. This study was to investigate the effect of RAD containing human renal proximal tubule cells (hPTC) on porcine model with MODS and ARF. It is necessary to get this date for further clinical application of RAD.Methods (1) Primary culture, subculture and identification of human renal proximal tubule cells (PTC). (2) Fabrication of RAD with hPTCs. (3) Establishment of porcine model with MODS and ARF. All pigs were performed by cecal ligation and puncture (CLP) and bilateral ureteral ligation (UL). (4) Pigs with MODS and ARF were placed on CVVH with either a RAD (A group) or a sham RAD without cells (B group) or without blood purification (C group). (5)Serum ALT, BUN, Cr, electrolytes and tumor necrosis factor-a(TNF-a), interleukin-10(IL-10), arterial blood gas were tested at 0,8,16,24 hour after the beginning of the treatment. Vital signs and survival time were recorded.Results (l)After 5-6 days, the cultured cells reached confluence, displaying the typical cobblestone appearance and could be subcultured till 7-9 passages. Method of cell morphology and staining of specific marker validated them as human PTC. (2) Effect of RAD constructed with human renal cells on porcine model with MODS and ARF showed that: â‘  Mean arterial pressure(MAP, mmHg) was significantly higher in group A than group B and C at 24 hours ((88.13±7.62) vs. (63.50±11.82) vs. (53.50±2.52))(P<0.01);(2)The values of BUN, Cr , K⁺, PaO₂, HCO₃,were similar during the treatment periods between group A and B (P>0.05),which were better than those of group C; â‘¢ In A group, TNF-α...