Effects of oral neomycin and kanamycin in chronic uremic patients: I. Urea metabolism

Effects of oral neomycin and kanamycin in chronic uremic patients: I. Urea metabolism. The fate of portal ammonia derived from intestinal urea degradation was examined in 15 experiments in patients with chronic renal failure. The kinetics of labelled urea metabolism were studied before and again during the administration of oral neomycin or kanamycin. Detectable absorption of both drugs generally occurred, but urea clearance and estimated glomerular filtration rate did not significantly change during antibiotic administration. In seven experiments a significant fall in urea degradation (65% to 95%) occurred during antibiotic administration. Analysis of the effect of antibiotics was confined to these seven experiments. In the control periods, there were no differences in urea metabolism or renal function between these patients and those in whom urea degradation was not suppressed. If ammonia derived from urea degradation is converted back to urea in the liver, then suppression of degradation would lead to an equal decrease in urea production, and the difference between production and degradation ("appearance") would remain constant. However, if urea-derived ammonia is used for protein synthesis, suppression of degradation would permit the formerly degraded urea to appear in urine and body fluids and thus to increase measured urea appearance. In these seven experiments, we found no change in urea appearance during antibiotic administration. We conclude that portal ammonia is reincorporated into urea in chronic renal failure and is not utilized significantly for protein synthesis. Effets de la neomycine et de la kanamycine administres par voie orale a des malades atteints d'uremie chronique: I. Metabolisme de l'uree. Le devenir de l'ammoniac portai provenant de la degradation intestinale d'uree a ete etudie chez 15 malades atteints d'insuffisance renale chronique. Les cinetiques du metabolisme de l'uree marquee ont ete etudiees avant puis pendant l'administration orale de neomycine et de kanamycine. Une absorption decelable de chacune des deux drogues a ete observee le plus souvent mais la clearance de l'uree et le debit de filtration glomerulaire mesure n'ont pas ete modifies de facon significative par l'administration de ces antibiotiques. Chez sept des 15 malades etudies une diminution significative de la degradation d'uree (65% a 95%) est survenue pendant la prise d'antibiotiques. L'analyse de l'effet des antibiotiques n'a ete realisee que chez ces sept malades. Au cours de la periode controle il n'y avait pas de differences dans le metabolisme de l'uree ou la fonction renale entre ces sept malades et les huit autres. Si l'ammoniac provenant de la degradation de l'uree est a nouveau converti en uree dans le foie la suppression de la degradation devrait aboutir a une augmentation equivalente de la production d'uree et la difference entre la production et la degradation ("apparition") demeurerait constante. Mais si de l'ammoniac provenant de l'uree est utilise pour la synthese proteique la suppression de la degradation devrait permettre a l'uree non degradee d'apparaitre dans l'urine et les liquides corporels et d'augmenter l'apparition d'uree. Nous n'avons observe aucune modification de l'apparition d'uree chez ces sept malades au cours de l'administration d'antibiotiques. Nous concluons que l'ammoniac portai est converti en uree au cours de l'insuffisance renale chronique et n'est pas utilise de facon significative pour la synthese des proteines.