RENAL PROCESSING OF LOW-MOLECULAR WEIGHT PROTEINS

Previous renal clearance studies provided quantitative data concerning renal reabsorption of proteins while the simultaneous processes of renal accumulation and degradation remain, to a great extent, insufficiently investigated. Thus, it was the aim of this study to measure renal reabsorption of egg-white lysozyme at various lysozyme concentrations and to relate the corresponding accumulation and degradation of lysozyme to the lysozyme transport rates in intact rats and isolated perfused rat kidneys. Lysozyme (with 125I-lysozyme in certain experiments), was continuously infused i.v. or added to the perfusate to achieve plasma (or perfusate) concentrations of lysozyme (PLY) of approximately 50, 500 or 1000 mg .cntdot. l-1 for periods of time varying between 3 and 120 or 150 min. Clearances of inulin and lysozyme or the total content of radioactivity and the trichloroacetic acid (TCA)-soluble radioactivity in the kidney tissue were determined at the end of clearance or accumulation periods. Additionally the perfusate concentration of the metabolite tyrosine was measured by high performance liquid chromatography (HPLC). The reabsorption rates of lysozye (TLY) were concentration-dependent in both intact rats and isolated perfused rat kidney. After 25 min of lysozyme infusion, the lysozyme reabsorption rates amounted to 37, 245 and 331 .mu.g .cntdot. min-1 .cntdot. g-1 kidney at the above lysozyme concentrations. After the same infusion time, the accumulation rates of lysozyme were 8, 59 and 118 .mu.g .cntdot. min-1 g-1 kidney. The difference between the transport rate and accumulation rate should represent the renal degradation rate of lysozyme appeared to increase in a time- and concentration-dependent manner. The renal lysozyme degradation is of limited capacity as shown by measuring directly the release of the amino acid tyrosine by using HPLC. Renal degradation of lysozyme was almost totally inhibited by gentamicin in the presence of significant transport of lysozyme. This also demonstrates the ability of the rat kidney to reabsorb and accumulate large amounts of the cationic low MW protein lysozyme without ultrastructural changes at plasma concentrations of lysozyme as high as 500 mg .cntdot. l-1. Transmission electron microscopy indicated an increase in the number of endocytic vesicles and lysosomes at 1000 mg .cntdot. l-1 plasma concentration of lysozyme after a 30 min infusion.