Publications (2)2.66 Total impact
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ABSTRACT: In peritoneal dialysis, the usage of automated peritoneal dialysis (APD) has been steadily increased. As APD means larger volumes of solution and more frequent contact times with fresh dialysate, an additive negative impact on biocompatibility data, exceeding the known effect of conventional PD fluids, seems possible. For an in-vitro comparison of APD and CAPD, a new cell culture system has recently been established. A double chamber cell culture system with human mesothelial cells on top of a permeable membrane and growth medium beyond was used for mimicking CAPD and APD. Reflecting the in vivo equilibration pattern, we compared an eight-hour CAPD with a CCPD setting, using a conventional PD solution. Cell viability was assessed with a MTT assay and cell function via constitutive and stimulated IL-6 release. CA125 was measured as a parameter of mesothelial cell integrity, and TGF-1beta was measured as an index of induction of fibrosis. Both the CAPD and the CCPD mode resulted in a significantly lower MTT assay and stimulated IL-6 release compared to growth medium. TGF-1beta and CA125 release did not differ between the PD modes and control. The CAPD and the CCPD mode itself did not differ with regard to MTT assay, IL-6 release, TGF-1beta and CA125 generation. From the in-vitro model imitating the acute exposure of mesothelial cells with conventional PD fluid in a CCPD and CAPD mode, there is no evidence that APD, due to the larger volumes of solution and more frequent contact times with fresh dialysate, has an acute, additive negative impact on biocompatibility parameters indicative for peritoneal host defense, mesothelial cell integrity and peritoneal fibrosis.
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ABSTRACT: In peritoneal dialysis (PD), neutrally buffered PD fluids with lower concentrations of glucose degradation products (GDP) have tested superior to conventional fluids in terms of biocompatibility. However, conventional in vitro studies provoke debate because, due to the lack of subsequent equilibration with the blood, they do not resemble the true intraperitoneal situation of PD. We established a double-chamber cell culture system with peritoneal mesothelial cells seeded on top of a permeable membrane, with a physiological buffer below. Thus adequately reflecting the in vivo equilibration pattern, we compared a conventional fluid with a neutral bicarbonate/lactate-buffered PD solution. Using an exchange pattern adapted from an 8-hour continuous ambulatory PD regimen, cell viability was assessed with an MTT assay, and cell function via constitutive and stimulated interleukin (IL)-6 release. As an indicator of potential induction of fibrosis and as a parameter of mesothelial cell integrity, respectively, transforming growth factor-beta 1 (TGF-beta1) generation and cancer antigen 125 (CA125) release were measured. The conventional solution significantly compromised mesothelial cell viability and function in terms of mitochondrial activity (p < 0.05) and stimulated IL-6 release (p < 0.05). The bicarbonate/lactate fluid had no effect on cell viability or IL-6 release and turned out to be equivalent to the properties of the growth medium. Whereas lactate-incubated cells did not respond to IL-1beta stimulation, bicarbonate/lactate-treated cells adequately increased IL-6 release after stimulation (p < 0.0005). Release of TGF-beta1 and CA125 did not differ between the different fluids and the control. Due to the sustained equilibration process, the double-chamber cell culture model allows a more realistic insight into mesothelial cell viability and function in terms of PD. As in classic in vitro studies, an adverse effect of conventional PD solutions on mesothelial cells was overt in the present cell culture system. The neutral bicarbonate/lactate-buffered fluid with low GDP content, however, did not interfere with mesothelial cell vitality or function, indicating superior biocompatibility.