P0074 PP IN VIVO MEASUREMENT OF UREA PRODUCTION AND RECYCLING WITH [15N2]UREA: UNDERESTIMATION OF UREA RECYCLING RATE BY CURRENT STANDARDS

Abstract

Introduction: Measurements of urea rate of appearance (Ra) and rate of recycling (RaR) are commonly applied in research into the nutritional and metabolic status of children. The precision of the isotopic plateau calculations during the primed, constant tracer infusion protocol remains unclear. Methods: In 8 fed and 6 fasted piglets, we measured total body water with [2H2]water and performed a 10 h primed constant i.v. infusion of [15N2]urea. Plasma urea enrichments of [ 15N2]urea and [15N1]urea were determined by GCMS and used for plateau calculations of Ra and RaR. Urea pool and urea Ra were compared with results of one, two and three compartmental modeling, and with simulations extending to 20 and 100 h tracer infusion. Results: Differences between fed and fasted animals were not significant. Urea pool (mean ± SEM) was 2.2 ± 0.2 mmol.kg−1 (NS vs. compartmental modeling: 2.1 ± 0.2 mmol.kg−1). From plateau calculations, urea Ra was 245 ± 20 mumol.kg−1.h−1. RaR accounted for 5.9% of Ra. [15N1]urea plateau was not present after 10 h infusion; simulations showed achievement of plateau after 33–100 h, with RaR accounting for 11.6% of Ra (p=0.001 vs. plateau model). Compartmental and simulated plateau calculations showed agreement for total Ra and RaR, but not with the actual plateau calculations up to 10 h.Table 1: Urea rate of appearance (Ra) and recycling (RaR): mumol.kg−1.h−1Conclusion: Plateau calculations in the [15N2]urea infusion protocol show lower accuracy and underestimate recycling by ~50% as compared to simulated plateau (duration 20, 100 h) and compartmental modeling. This suggests that short term (<10 h) protocols applied in fed and fasted individuals underestimate urea gut recycling, unless compartmental modeling or simulations of [15N1]urea plateau are used.