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A Method for Determination and Simulation of Permeability and Diffusion in a 3D Tissue Model in a Membrane Insert System for Multi-well Plates
Published on: February 23, 2018
Correction of sodium sieving for diffusion from the circulation
M M Zweers1, A L Imholz, D G Struijk
1Department of Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Abstract:
Transcellular water transport (TCWT) can be estimated by Na- sieving. However, the assumption that the initial Na+ dialysate concentration (D0) is equal to the initial plasma concentration (P0) is not true for each patient. The difference leads to Na+ diffusion from the circulation to the dialysate, which diminishes the Na+ sieving. A model was developed to distinguish transcellular water transport from Na+ diffusion. We previously found evidence that the mass transfer area coefficient of urate (MTACurate) was similar to the MTACNa+. The MTAC is the product of the elimination constant (ke) and the volume of distribution (VD), the mean intraperitoneal volume. Because VD is known, the ke Na+ in each patient can be equated with the ke urate. The Na+ mass transfer from the circulation to the dialysate by diffusion can then be calculated for any time point during a dwell (Dt). Dt was subtracted from the measured Na+ dialysate concentration at 60 minutes. The corrected D/P Na+ then represents the actual Na+ sieving. Using 3.86% glucose dialysate, this approach was investigated in 15 stable peritoneal dialysis (PD) patients (normUF) and in 9 PD patients with low ultrafiltration (lowUF, < 400 mL/4 hours). The MTACurate was calculated according to Waniewski (W) and according to the Garred model (G). Similar calculations were also performed for the MTAC of creatinine (MTACcreat). Initial D/P Na+ was not different between the groups. When no diffusion correction was made, D/P60 Na+ in the lowUF group (median 0.898, range 0.870-0.949) was significantly higher (p < 0.025) than D/P60 Na+ in the normUF group (median 0.881, range 0.816-0.899). The difference disappeared after diffusion correction regardless of the correction model applied. However, at 240 minutes, D/P Na+ in the normUF group was significantly lower than in the lowUF group (median 0.880, range 0.839-0.952 vs median 0.942, range 0.866-0.987; p < 0.004). Even after correction, D/P Na+ in the normUF group was significantly lower: 0.847 normUF versus 0.893 lowUF (Wurate, p < 0.005); and 0.842 normUF versus 0.890 lowUF (Gcreat, p < 0.003). The correlation between the Wurate (the best theoretical diffusion correction) and Gcreat (the least) was: y = 0.99x + 0.0037. Furthermore, Bland and Altman analyses of Wurate and Gcreat at both 60 and 240 minutes resulted in random distribution around the means, with a slight overestimation in relation to the magnitude of Gcreat, as was expected. Gcreat can be used to make an accurate estimation of the contribution of Na+ diffusion in the time course of D/P Na+. It provides a simple way to more precisely determine Na+ sieving, and therefore TCWT. In conclusion, to avoid overestimation of impaired channel-mediated water transport, a Na+ diffusion correction should be made when D0 is not equal to P0 or in the case of a large vascular surface area.
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