Middle molecule definition in terms of membrane permeability

The term "Middle Molecules" originated as an operational definition for metabolites whose removal rate in the dialyzers of the 1970s was limited principally by the devices then used. Improvements in both the device designs and membrane performance require that we reexamine the definition. This discussion presents the relationship between membrane properties and operating conditions so that a general prediction can be made for metabolite clearance using either dialysis or hemofiltration. The current theories of solute/solvent coupling during membrane transport require that the designer and user consider not only the intrinsic membrane properties, but also the ultrafiltration velocity applied during therapy. This is particularly important in the use of hemofiltration, but may also be significant when high ultrafiltration rate dialyzers are employed. To provide a working definition of middle molecules, we reference the transport of solutes of increasing hydrodynamic radius to the transport of urea. Data for a series of membranes used in current and experimental devices will be presented.