AGING MEDIATED CHANGES IN RENAL EXCRETION OF ORGANIC ANIONS

衰老介导的肾脏有机阴离子排泄变化

• 批准号: 6356553
• 负责人: MICHELLE BAZIL
• 金额: $ 10.16万
• 依托单位: LONG ISLAND UNIVERSITY BROOKLYN CAMPUS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2001-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6356553
• 关键词: AGING; MEDIATED; CHANGES; RENAL; EXCRETION

The broad long term objective of this research is to characterize the effects of aging on renal drug excretion. Although it is well established that becoming older is accompanied by anatomic and physiologic changes in renal function, there is a paucity of data regarding the differential effects of aging on the individual mechanisms of renal excretion of medications: filtration, secretion and reabsorption. The first specific aim of the research is to establish the isolated perfiised rat kidney (IPK) model as a useful tool for studying the effects of aging on physiologic renal function and renal clearance. Establishing the IPK as a model of renal drug disposition in geriatric subjects would allow correlation between aging and the numerous factors which affect renal drug excretion. A second aim of the research is to test the validity of the "Whole Nephron Hypothesis" which assumes that reductions in glomerular filtration secondary to aging or disease are accompanied by parallel reductions in secretion and reabsorption. Whereas this hypothesis is the basis for making dosage adjustments based on glomerular filtration rate (GFR), reports in the literature suggest that tubular secretion of certain medications can be maintained in the presence of decreased OFR. Studying the effects of aging on the renal excretion para-aminohippurate and acetazolamide, compounds of contrasting degrees of renal extraction, will permit assessment of the linearity between filtration and secretory mechanisms of the kidney. These findings could challenge present guidelines for GFR-based dosing of medications in geriatric patients and possibly reduce the incidence of drug-related morbidity in this patient population.

本研究的长期目标是确定衰老对肾脏药物排泄的影响。虽然已经确定变老伴随着肾脏功能的解剖和生理变化，但关于衰老对肾脏药物排泄的个体机制（过滤、分泌和重吸收）的差异影响的数据缺乏。本研究的第一个具体目的是建立离体纯化大鼠肾（IPK）模型，作为研究衰老对生理肾功能和肾清除率影响的有用工具。将IPK建立为老年受试者肾脏药物处置的模型，将允许衰老与影响肾脏药物排泄的众多因素之间的关联。该研究的第二个目的是检验“全肾元假说”的有效性，该假说认为继发于衰老或疾病的肾小球滤过减少伴随着分泌和重吸收的平行减少。虽然这一假设是根据肾小球滤过率（GFR）调整剂量的基础，但文献报道表明，在OFR降低的情况下，某些药物的小管分泌可以维持。研究衰老对肾脏排泄对氨基马粪酸酯和乙酰唑胺的影响，这两种化合物的肾脏提取程度不同，将允许评估肾脏过滤和分泌机制之间的线性关系。这些发现可能会挑战目前针对老年患者基于gfr给药的指南，并可能降低该患者群体中药物相关发病率。