RBP Catabolism Role of the Kidneys

These considerations effectively describe the role of the kidney in the metabolism of free uncomplexed RBP. However, since neither TTR nor the RBP-TTR complex would normally be filtered appreciably (because of their larger size), the quantitative importance of the kidneys in the metabolism of RBP would depend to a major extent on the proportion of RBP present in plasma in the free uncomplexed state. If, as estimated above, free RBP normally represents approximately 4% of circulating RBP, and if the glomerular membrane were fully permeable to uncomplexed RBP, then glomerular filtration and renal catabolism would account for the metabolic clearance of 7-8 liters of plasma per day in a 70-kg human. This represents a large proportion of the normal daily turnover of RBP (see discussion below) and confirms the major quantitative role of the kidney in the overall metabolism of RBP. 

RBP has been found in relatively large amounts in the urine from patients with tubular proteinuria (Peterson and Berggard, 1971). Much is known about urinary protein excretion of Japanese patients with chronic cadmium poisoning (Kanai-er al., 1972a,b). These patients manifest tubular proteinuria and the excretion of considerable amounts of low-molecular-weight proteins, including RBP. The urinary excretion of RBP has been induced in a rabbit (Muto et al., 1976) and in a rhesus monkey (Nomiyama et al., 1981) by chronic poisoning with cadmium. Studies of the role of the kidney in RBP metabolism have also been carried out in rats with various kinds of experimentally induced renal lesions (Peterson et al., 1974). These various reported observations are all consistent with the above postulated role of the kidney in RBP metabolism. 

No information is avaUable about the possible role of tissues other than the kidney in the catabolism of RBP. The tissue sites and mechanisms involved in the catabolism of TTR are not known. 

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