Monday, November 3, 2008

Middle Molecules

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.


Unknown said...

Molecular weight of light chains is 25 kDa, but this is mainly referred to kappa light chains, that are monomeric; lambda light chains are usually dimeric, thus their MW is 50 kDa, not dialyzable with most membranes (super-flux membranes cut-off is around 50 kDa), except with high cut-off membranes.
You need a large pore membrane to dialyze paraproteinemias.

nathanhellman said...

Thanks for the comment!

That makes sense regarding having to use a super-flux membrane for dialyzing paraproteinemias.

My understanding is that the reason this is not that effective in treating myeloma kidney is because the antibody is rapidly re-synthesized and thus one would need nearly constant dialysis in order to prevent renal damage from occurring.

Unknown said...

It is not useful to dialyze a myeloma kidney without chemotherapy treatment; but if you stop the paraprotein production with chemotherapy (whatever protocol it is) you can dialyze with a large pore dialyzer in order to avoid further kidney damage.
There some trial working in that area. We will see the results