Middle molecules in patients with pre-dialysis chronic renal failure: a comparative clearance study

Residual renal function is an important parameter int he design of dialysis regimens. In this study residual renal clearance of potential uremic toxins in the middle molecular weight range (originally thought to be 300-2000 daltons, but now considered close to 300-700 daltons) was investigated in patients with predialysis chronic renal failure. Middle molecules were isolated from uremic sera and urines by gel filtration and further separated by gradient elution chromatography to give 7 to 8 definable uremic middle molecular weight species. The renal clearances of middle molecule fractions were compared with simultaneously measured endogenous creatinine, urinary inulin and single short inulin clearance. The four middle molecule fractions which were quantitated (7a, b, c and d) were found to be freely filtered and to have renal clearances in end stage renal failure approximately equal to the endogenous creatinine clearance. Thus, renal handling of middle molecules is strikingly different from that of other peptides of peptide hormones in that the species do not appear to be catabolized, secreted or reabsorbed by the renal tubules to any significant degree.