Accumulation and excretion of middle molecules.

The accumulation and excretion of uremic middle molecules (MM) were assessed in 97 non-dialyzed azotemic patients with varying degrees of renal insufficiency. For comparison the excretion rates of MM were estimated in 12 normal subjects. By the use of combined gel filtration and ion exchange gradient elution chromatography the U-V absorbing fractions (7a, 7b, 7c, 7d, 7e, 7f and 7g) with middle molecular characteristics were isolated and quantified in uremic plasma. Accumulation of MM in sufficient quantities to be measured in the analytical system occurred only in patients with advanced renal failure with endogenous creatinine clearance below 11 ml/min. These MM fractions were either undetectable or present in trace quantities in the plasma of normal individuals. The excretion rates of certain MM (fractions 7c and 7f) were higher in uremic patients than in normal subjects, suggesting that the accumulation of these fractions occurred as a consequence not only of reduced urinary excretion but also of the enhanced production rate. The excretion rates of other fractions (7a, 7b and 7g) were of the same magnitude in uremic patients as in normal individuals. Renal clearances of the MM fractions were equal to or higher than endogenous creatinine clearance.