Excretion of progastrin products in human urine

The renal handling of carboxyamidated gastrins, NH2-terminal progastrin fra gments, and glycine-extended gastrins was examined in healthy volunteers. T he respective urinary clearances after a meal amounted to 0.09 +/- 0.02%, 0 .17 +/- 0.04% (P < 0.05), and 0.04 +/- 0.01% (P < 0.01) of the glomerular f iltration rate. During intravenous infusion of carboxyamidated gastrin-17, progastrin fragment-(1-35), and glycine-extended gastrin-17, the respective urinary clearances amounted to 0.08 +/- 0.02, 0.46 +/- 0.08, and 0.02 +/- 0.01%, respectively, of the glomerular filtration rate. The metabolic clear ance rate of the three peptides was 24.4 +/- 1.3, 6.0 +/- 0.4, and 8.6 +/- 0.7 ml.kg(-1).min(-1). A maximum rate for tubular transport or degradation of the peptides could not be determined, nor was a renal plasma threshold r ecorded. Plasma concentrations and urinary excretion rates correlated for g astrin-17 and progastrin fragment-(1-35) (r = 0.94 and 0.97, P < 0.001), wh ereas the excretion of glycine-extended gastrin diminished with increasing plasma concentrations. We conclude that renal excretion of progastrin produ cts is negligible compared with renal metabolism and that renal handling of the peptides depends on their molecular structure. Hence, the kidneys exhi bited a higher excretion of NH2-terminal progastrin fragments than of carbo xyamidated and especially glycine-extended gastrins.