Renal handling of middle molecules in uremic patients and in the isolated rat kidney

Renal handling of uremic middle molecules (MW 300-2000 daltons) was investigated (1) in the diseased kidney in nine patients suffering from chronic renal failure in the pre-dialysis phase, and (2) in the isolated perfused rat kidney using hemofiltrate and albumin (5 gm/100 ml) containing perfusate. Middle molecules clearances are compared to the simultaneously measured inulin and creatinine clearances. Four middle molecule fractions (peak 7a, 7b, 7c, and 7d) were quantitated after high-speed gel filtration and gradient elution chromatography and found to be freely filtered (= middle molecules clearances not differing from inulin and creatinine clearances) in uremia in man. In the "intact" (isolated perfused) rat kidney, elimination also takes place by glomerular filtration (peak 7a, 7c at high perfusate levels). Peaks 7b and 7d are slightly reabsorbed (15% and 25%, respectively, of filtered load), whereas 7c1 is secreted up to 220% of inulin clearance at low perfusate levels. No renal catabolism and high urinary excretion of middle molecules clearly indicate different renal handling of this species in comparison to other peptides or peptide hormones of the same molecular weight range.