Dialyzer technology has evolved to allow production of high-flux membranes, with both increased water (ultrafiltration coefficient > 20 ml/h/mmHg) and solute removal. Small solute clearances can be increased by fiber surface undulations and internal constriction, or other designs to create an internal vortex flow. Larger solute clearances can be achieved by increased internal diafiltration by creating oscillations in the transmembrane pressure, creating resistance to blood flow within the dialyzer, either by reducing the internal diameter of the fibers or by increasing the dialyzer length. Although nanotechnology-produced dialyzer membranes have both increased solute removal mass and enlarged the spectrum of solutes cleared, many are predominantly intracellular or bound to plasma proteins. As such, the rate limiting step is often the movement from intracellular sites to the plasma water or the rate of dissociation from plasma proteins. As such, the clearance of such solutes is time dependent and can potentially be overcome by longer and more frequent dialysis sessions.