UREMIA, ACIDOSIS & DIALYSIS ON PROTEIN METABOLISM: LONGITUDINAL LEUCINE KINETICS

尿毒症、酸中毒

• 批准号: 6118556
• 负责人: VICTORIA S LIM
• 金额: $ 0.16万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6118556
• 关键词: biomedical resource; female; human subject; male; prosthesis; proteins; spectrometry; urinary tract

Uremia and dialysis are viewed as catabolic processes resulting in malnutrition in chronic renal failure (CRF) patients. To sort out the effects of uremia, acidosis and dialysis on protein metabolism, we measured leucine flux in CRF patients before and after initiation of maintenance dialysis. Whole body leucine flux was measured by primed-constant infusion of L[1-13C]leucine in 9 CRF patients longitudinally; twice before and once after initiation of maintenance dialysis [D]. Before dialysis, one leucine flux was measured when the patients were acidotic [A], and the other, when acidosis was corrected with NaHCO3[NA]. Five normal subjects underwent one single leucine flux measurement to serve as control [N]. Both patients and normal subjects consumed a constant diet for 6 days and leucine flux was measured on the 7th day 12 hr. post-absorption. Diet for the CRF patients was identical during the three periods. Plasma L[1-13C] leucine and L[1-13C]KIC were measured by gas c hromatography/mass spectrometry and expired 13CO2 by isotope ratio spectrometry. Leucine kinetics were calculated using standard equations. Plasma CO2 were 19,26 and 31 mmol/L in A, NA and D periods, respectively. All kinetic results ((mol/kg/hr) are presented as means (SD in the order of A, NA, D and N, and CRF values that are statistically different from N are identified [*]. The amount of leucine release from endogenous protein breakdown [Ra or Q] were 101(12*, 95(9*, 113(22 and 117(6. Leucine oxidation [C], quantity of leucine irreversibly oxidized to CO2, were 16.5(5.4, 9.7(3.7*, 12.3(3.0* and 23.2(3.1. Leucine protein incorporation [S] were 85(10, 85(8, 101(19 and 94(6. The S of 101 in CRF patients at period D was statistically higher than those during A and NA periods. These data indicate that when acidosis was corrected, CRF patients adapted to lower protein intake by reducing amino acid oxidation and protein degradation, and maintained protein synthesis at normal level . Metabolic acidosis impaired the down regulation of amino acid oxidation. Maintenance dialysis treatment longitudinally restored protein flux to normal and increased protein synthesis. The general notion that uremia and dialysis are protein catabolic are not supported by this work.

尿毒症和透析被视为分解代谢过程， 慢性肾衰竭（CRF）患者的营养不良。 是梳理 尿毒症、酸中毒和透析对蛋白质代谢的影响， 在开始治疗之前和之后， 维持性透析。 全身亮氨酸通量通过 预充-恒定输注L[1- 13 C]亮氨酸治疗9例慢性肾功能衰竭 纵向;开始维持治疗前两次，开始维持治疗后一次 透析[D]。 在透析之前，当在透析前测定亮氨酸通量时， A组为酸中毒，B组为酸中毒纠正后 用NaHCO 3 [NA]。 5名正常受试者接受了一个单一的亮氨酸 通量测量作为对照[N]。 患者和正常人 受试者连续6天食用恒定的饮食， 在第7天吸收后12小时测量。 CRF的饮食 患者在这三个阶段是相同的。 血浆L[1- 13 C] 亮氨酸和L[1- 13 C]KIC用气相色谱/质谱法测定 通过同位素比光谱法测定呼出的13 CO2。 亮氨酸 使用标准方程计算动力学。 血浆CO2 A、NA和D期分别为19、26和31 mmol/L。 所有动力学 结果（（mol/kg/hr）表示为平均值（SD，顺序为A，NA， D和N，与N有统计学差异的CRF值为 已识别[*]。 内源性蛋白质释放亮氨酸的量 分解[Ra或Q]分别为101（12*）、95（9*）、113（22）和117（6 *）。 亮氨酸 氧化[C]，亮氨酸不可逆氧化为CO2的量， 16.5（5.4）、9.7（3.7*）、12.3（3.0*）和23.2（3.1。 亮氨酸蛋白 掺入[S]分别为85（10）、85（8）、101（19）和94（6）。 101的S CRF患者在D期显著高于A期 NA时期。 这些数据表明，当酸中毒得到纠正， CRF患者通过减少氨基酸来适应低蛋白质摄入 氧化和蛋白质降解，并保持蛋白质合成， 正常水平。 代谢性酸中毒损害了 氨基酸氧化 纵向维持透析治疗 使蛋白质流量恢复正常并增加蛋白质合成。 的 一般认为尿毒症和透析是蛋白质分解代谢， 支持这项工作。