RENAL FAILURE:PATHOPHYSIOLOGY & POSSIBLE PREVENTION

肾衰竭：病理生理学

• 批准号: 3226555
• 负责人: JACQUES J BOURGOIGNIE
• 金额: $ 18.9万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-07-01 至 1992-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3226555
• 关键词: baboons; blood pressure; chronic renal failure; creatinine; dietary calcium; dietary lipid; dietary proteins; dietary sodium; electron microscopy; excretion; fasting; glomerular filtration; glomerular filtration rate; growth factor; hemodynamics; kidney circulation; kidney metabolism; nutrition related tag; p aminohippurate; peptidyl dipeptidase A; phosphorus; protease inhibitor; protein metabolism; protein transport; proteinuria; renal tubular transport; urea

The program seeks to rest in non-human primate the proposal that protein may be responsible for progressive loss of GFR in chronic renal insufficiency and that a reduced protein diet may be protective. The investigation, initiated 24 months ago, will be conducted in baboons (Papio hamadryas) with 5/8 reduction in renal mass. Two groups, fed either an 8% or a 25% protein diet, will be compared. The diets are isocaloric and equal in fat, sodium, phosphorus, calcium, oligoelement and vitamin content. The following questions are addressed: Does a glomerulopathy develop in baboon after renal mass ablation and, if so, is the rate of progression of renal dysfunction influenced by protein intake? A second aim, to be initiated only after the primary aims are achieved, will assess the effects of angiotensin converting enzyme inhibition on hypertension and progression of renal insufficiency. Serial studies will compare a) Fasting renal hemodynamics: Whereas clearances of inulin, para- aminohippurate, and endogenous creatinine per kg body weight are significantly higher in 25% than in 8% protein fed baboons, do they decrease faster with high than with low protein diet? Dietary intake will be assessed from sodium, potassium and urea nitrogen excretion in 24hr urines; c) Systemic arterial blood pressure: Is progressive renal dysfunction related to differences in arterial blood pressure? Measurements a to c will be obtained every 4 months in awake animals, d) Morphology and ultrastructure of the viable portion of the remnant kidney will be examined every 18 months by light and electronmicroscopy and ultimately, by quantitative morphometrics; The majority of studies that implicate protein in progressive renal disease have been carried out in rodents. This study should provide definitive information on the role of protein and on the potential benefits of a reduced protein intake in renal insufficiency in primates. The results should be directly relevant to humans.

该计划试图在非人类灵长类动物身上提出这样的建议：蛋白质 可能是慢性肾病患者 GFR 逐渐丧失的原因 不足，减少蛋白质饮食可能具有保护作用。 这 24 个月前启动的调查将在狒狒 (Papio Hamadryas）肾质量减少 5/8。 两组，喂食 8% 或 25% 蛋白质饮食，将进行比较。 饮食是等热量的并且 脂肪、钠、磷、钙、微量元素和维生素含量相同 内容。 解决以下问题：肾小球病是否会导致肾小球病？ 狒狒在肾肿块消融后发生的情况，如果是的话，发生率是 蛋白质摄入量会影响肾功能障碍的进展吗？ 一秒钟 目标仅在实现主要目标后启动，将评估 血管紧张素转换酶抑制对高血压的影响 肾功能不全的进展。 系列研究将比较a) 空腹肾血流动力学：而菊粉的清除率，副 每公斤体重的氨基马尿酸和内源性肌酐是 25% 的蛋白质喂养的狒狒明显高于 8% 的狒狒，是吗？ 高蛋白饮食比低蛋白饮食下降得更快？ 饮食摄入量会 通过24小时内钠、钾和尿素氮的排泄来评估 尿液； c) 全身动脉血压：肾性进行性血压升高 与动脉血压差异相关的功能障碍？ 每 4 个月对清醒的动物进行一次 a 至 c 的测量，d) 残肾存活部分的形态和超微结构 每 18 个月通过光学和电子显微镜检查一次， 最终，通过定量形态计量学；大多数研究表明 与进行性肾病有关的蛋白质已在 啮齿动物。 这项研究应该提供关于作用的明确信息 蛋白质以及减少肾脏蛋白质摄入量的潜在益处 灵长类动物缺乏。 结果应直接相关 人类。