The term “Middle Molecules” is a little confusing, in part due to its evolving definition. It was initially used to describe anything not dialyzed off by the older dialyzer membranes of the 1970s, which predominantly filtered out only small, water-soluble molecules such as potassium, for example. The advent of newer, “high-flux” dialyzers has enabled the removal of higher molecular weight species, but to a variable degree.
The European Uremic Toxin Work Group has defined the term middle molecule to be between 500 Daltons – 60 kD. There is still a strong thought that as-yet-unidentified unfiltered middle molecules may be a major reason for the unusually high cardiovascular mortality rate of ESRD patients.
Here is a helpful list of molecular weights of some common substances:
BUN (0.06 kD). Obviously, not a middle molecule; small, cleared rapidly.
Creatinine (0.113kD). Same as BUN: cleared rapidly.
Vitamin B12 (1.355 kD). A middle molecule of lower MW which is cleared by most modern dialyzers.
B2-microglobulin (11.8kD). One of the few middle molecules whose accumulation has been shown to be associated with a real medical condition: b2-amyloidosis. Newer generation dialyzers provide good clearance of b2-microglobulin and have made the clinical entity of b2-amyloidosis much more rare.
light chain (25kD). Light chains are small enough to get dialyzed–providing some rationale for dialyzing patients with paraproteinemias (though the clinical evidence for this being effective is not very good).
albumin (66kD). Albumin is not a middle molecule–it is not appreciably dialyzed off, nor would it be desirable to do so.