Renal folate absorption and the kidney folate binding protein. I. Urinary clearance studies

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Abstract
The kidney possesses a high concentration of a folate binding protein (FBP) that resides primarily in the brush-border membrane (BBM) of the proximal tubular cells. To assess the possible involvement of this protein in renal conservation of folate we determined the urinary clearance, in rats, of three forms of folates with sharply different affinities for FBP. After single intravenous injection of 0.1- to 1.0-nmol doses of radioactive folates the urinary clearance based on radioisotope determination was in the sequence: folic acid > 5-methyltetrahydrofolate (5-CH3THF) .mchlt. methotrexate. At higher doses the urinary folate clearance was increased and the differences between the three injected forms were narrowed and were no longer noticeable at 100-nmol doses. Under conditions of continuous infusion to attain plasma folate levels of 2.3-5.7 pmol/ml, the urinary clearance based on chromatographic analyses of plasma and urine after correction for plasma folate binding was 0.20 ml/min for folic acid, 0,37 ml/min for 5-CH3THF, and 1.76 ml/min for methotrexate. These chromatographic analyses have also shown the presence in both plasma and urine of metabolites formed from infused folates. Metabolites found after infusion of folic acid include 5-CH3THF with a urinary clearance of 0.3 ml/min and an unknown with a urinary clearance of 0.8 ml/min. The latter metabolite appears also to occur in plasma and urine after infusion of 5-CH3THF. Infusion of methotrexate was associated with the appearance of a metabolite with a urinary clearance of 2.4 ml/min. This sequence of urinary clearance is in inverse order to the affinities of these three forms of folate for the kidney BBM FBP. By use of columns that contained FBP immobilized to Sepharose-4B matrix it was shown that folates with lower urinary clearance were more efficiently retained by these columns than folates with higher urinary clearance. These data are consistent with the proposal that renal tubular folate absorption is a saturable process that includes an initial step of folate binding to the BBM FBP.

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