Peritubular extraction

Disposition Aldesleukin is primarily eliminated by metabolism in the kidney. It is cleared from the circulation by both glomerular filtration and peritubular extraction with little or no bioactive protein excreted in the urine. 

Fig. 2.4 Renal elimination processes of peptides and proteins Glomerular filtration followed by either (a) intraluminal metabolism or (b) tubular reabsorption with intracellular lysosomal metabolism, and (c) peritubular extraction with intracellular lysosomal metabolism (modified from [76]).

The third mechanism is peritubular extraction of peptides and proteins from postglomerular capillaries and intracellular metabolism. Experiments using iodi-nated growth hormone (125I-rGH) have demonstrated that, while reabsorption into endocytic vesicles at the proximal tubule is still the dominant route of disposition, a small percentage of the hormone may be extracted from the peritubular capillaries [79, 86]. Peritubular transport of proteins and peptides from the baso-lateral membrane has also been shown for insulin [87] and the mycotoxin ochra-toxin A [88]. 

In humans, there are at least three clearance mechanisms by which IL-2 is removed systemically glomerular filtration, peritubular extraction, and an inducible receptor-mediated mechanism (Gibbons et al., 1995 Rabkin and Kitaji, 1983 Piscitelli et al., 1996). The inducible receptor-mediated clearance of IL-2 has not been observed in rats after multiple dosing despite IL-2 being active in this species. 

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