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Glomerular Filtration and Tubular Secretion of MAG-3 in the Rat Kidney

Karolinska Institute, Dept. of Clinical Physiology Danderyds Hospital, Stockholm and Dept. of Physiology and Medical Physics, Uppsala University, Uppsala, Sweden

Correspondence: For reprints contact: Roland Müller-Suur, Dept. of Clinical Physiology, Danderyds Hospital, S-182 88 Danderyd, Stockholm, Sweden.

ABSTRACT

Technetium-99m mercaptoacetyltriglycine (MAG-3) has recently been introduced as a new radiopharmaceutical for dynamic renal scintigraphy. To elucidate the mechanism of renal excretion, micropuncture experiments were performed in rat kidneys for direct measurements of glomerular filtration and tubular secretory capacity. Fluid of Bowman space was collected from superficial glomeruli and analyzed for its contents of [⁹⁹Tc]MAG-3, [¹²⁵I]hippurate and [³H]inulin during constant infusion of these compounds. The ratio of activity of ultrafiltrate to that of arterial plasma was 0.23 for MAG-3, 0.68 for hippurate and 1.04 for inulin which demonstrates that the filtrated amount of MAG-3 is only 23% of that of inulin, presumably because of higher plasma protein binding which was also measured in vitro and found to be 80 ± 1.5% for MAG-3 and 32 ± 2% for [¹²⁵I]hippurate.Proximal and distal tubules were also micropunctured and their tubular fluid as well as the final urine analyzed for the activity of hippurate and MAG-3. The tubular fluid to plasma ratio values along the nephron and in the final urine were all lower for MAG-3 than for hippurate, indicating a lower secretory capacity. From measurements of whole renal clearance, GFR and plasma protein binding the filtered amount of MAG-3 was 0.26 and of hippurate 0.87 ml/min·g kidney weight (p < 0.001) and the secreted amount 2.01 and 2.38 ml/min·g kidney weight (p < 0.05), respectively. We conclude that MAG-3 is predominantly excreted by tubular secretion and that the lower renal clearance of MAG-3 as compared with that of hippurate is a result both of a substantially decreased glomerular filtration and of a lower tubular secretion.