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Introduction: The flux of uremic toxin middle molecules through currently used hemodialysis membranes is suboptimal, mainly because of the membranes' pore architecture. Aim: Identifying the modifiable sieving parameters that can be improved by nanotechnology to enhance fluxes of uremic toxins across the walls of dialyzers' capillaries. Methods: We determined the maximal dimensions of endothelin, cystatin C, and interleukin – 6 using the macromolecular modeling software, COOT. We also applied the expanded Nernst-Plank equation to calculate the changes in the overall flux as a function of increased electro-migration and pH of the respective molecules. Results: In a high flux hemodialyzer, the effective diffusivities of endothelin, cystatin C, and interleukin – 6 are 15.00 × 10−10 cm2/s, 7.7 × 10−10 cm2/s, and 5.4 × 10−10 cm2/s, respectively, through the capillaries' walls. In a nanofabricated membrane, the effective diffusivities of endothelin, cystatin C, and interleukin – 6 are 13.87 × 10−7 cm2/s, 5.73 × 10−7 cm2/s, and 3.45 × 10−7 cm2/s, respectively, through a nanofabricated membrane. Theoretical modeling showed that a 96% reduction in the membrane's thickness and the application of an electric potential of 10 mV across the membrane could enhance the flux of endothelin, cystatin C, and interleukin – 6 by a factor of 25. A ΔpH of 0.07 altered the fluxes minimally. Conclusions: Nanofabricated hemodialysis membranes with a reduced thickness and an applied electric potential can enhance the effective diffusivity and electro-migration flux of the respective uremic toxins by 3 orders of magnitude as compared to those passing through the high flux hemodialyzer.