Renal handling of uremic middle molecules. a study with the isolated perfused rat kidney

Little is known of the normal renal handling of potential uremic toxins in the middle molecular weight (MMW) range (300-2,000 daltons). In this study the isolated rat kidney has been used as a model to investigate renal clearance and possible renal metabolic effects on uremic MMW species. Isolated rat kidneys were perfused with hemofiltrate from chronic renal failure patients containing 5% bovine albumin. Middle molecules (MM) were isolated from perfusates and urines by high-speed gel filtration (peak 7) and further separated by gradient elution chromatography to give 7-8 definable uremic MMW species (7a, b, c, etc.). Species 7b, d, e and f were tubularly reabsorbed by 15, 25, 23 and 34%, respectively, as indicated by simultaneous inulin clearances. 7a was freely filtered with negligible reabsorption. 1 MM (7c1) was found to be secreted by up to 220% at low perfusate concentrations, secretion being masked at high perfusate levels. No MMs were catabolized by the kidney, although one species (7c2) appeared to be synthesized. The results suggest that uremic MMs have differing biological or physicochemical activities as indicated by the selectivity of renal handling.