RENAL FAILURE: PATHOPHYSIOLOGY AND POSSIBLE PREVENTION

肾衰竭：病理生理学和可能的预防

基本信息

批准号：
3151256
负责人：
JACQUES J BOURGOIGNIE
金额：
$ 16.18万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
1976
资助国家：
美国
起止时间：
1976-07-01 至 1986-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3151256
关键词：
biological models dietary mineral disease /disorder prevention /control electrolyte balance glucagon hemodynamics homeostasis hyperkalemias insulin inulin kidney metabolism mineralocorticoids renal failure renal tubular transport saluresis uremias

项目摘要

The research program is designed to further explore the adaptations that attend the loss of functional renal mass. Dogs with chronic renal insufficiency (CRI) provide a model for long term studies, not only for the investigation of metabolic perturbations but for exploring amplified biological oscillations after an acute challenge. Thereby, CRI exchances the opportunity for uncovering physiologic compensating and regulatory mechanisms. A systematic investigation of the degree and nature of potassium disposition by extra-renal tissues after an acute potassium load is proposed. Particular emphasis is placed on the contribution of the sympathetic nervous system (circulating and synaptic catecholamines, Alpha and Beta mediated effects). Other factors (glucagon, insulin, aldosterone) will be studied in-vivo. In-vitro studies are proposed as well. Integrity of the calcium-phosphorus-parathyroid hormone-vitamin D axis in CRI will be defined. 1) The sequential effects of variations in dietary calcium and phosphorus and their effects on bone and renal responses to exogenous PTH will be assessed and correlated with circulating levels of parathyroid hormone and vitamin D metabolites; 2) the photoproduction of vitamin D will be examined; 3) the biochemical nature of the final steps in the PTH response will be detailed in normal and remnant kidneys by identifying and characterizing protein kinases(s), phosphorprotein phosphatase(s) and phosphoprotein substrates that undergo phosphorylation/dephosphorylation in tubular brush border membranes.

该研究计划旨在进一步探索适应参加功能性肾脏质量的损失。慢性肾脏的狗功能不全（CRI）为长期研究提供了一个模型，不仅为研究代谢扰动，但用于探索放大急性挑战后的生物振荡。因此，CRI交流发现生理补偿和调节的机会机制。对程度和性质的系统调查急性钾负荷后，肾外组织的钾处置提出了。特别强调交感神经系统（循环和突触儿茶酚胺，α 和β介导的效果）。其他因素（胰高血糖素，胰岛素，醛固酮）将在体内研究。还提出了体外研究。正直 CRI中的钙 - 磷酸 - 甲状旁腺激素 - 维生素D轴将是定义。 1）饮食钙和磷及其对骨骼和肾脏对外源PTH的影响将评估并与甲状旁腺的循环水平相关激素和维生素D代谢产物； 2）维生素D的光生源将被检查； 3）PTH最终步骤的生化性质通过识别和表征蛋白激酶（S），磷酸蛋白磷酸酶（S）和在经历磷酸化/去磷酸化的磷酸蛋白底物管状刷边界膜。