Molecular mechanisms linking proteinuria and sodium retention

蛋白尿和钠潴留之间的分子机制

• 批准号: nhmrc : 153931
• 负责人: Prof Carol Pollock
• 金额: $ 14.1万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/molecular-mechanisms-linking-sodium-retention/76788
• 关键词: Molecular; mechanisms; linking; proteinuria; sodium

The clinical association between protein loss in the urine and retention of salt, resulting in high blood pressure and progressive decline in kidney function, is well known. Under normal conditions, the kidneys filter 180 litres of water and reabsorb 1.7 kg of salt per day, a function which is principally performed by the kidney tubules in the kidney. Similarly the kidney tubule cells reabsorb and break down up to 3 grams of albumin per day. In the past, it has been considered that excessive protein loss in the urine is primarily due to problems in the filtering units of the kidneys, rather than due to abnormalities in the reabsorption of protein in the kidney tubules. However, we consider that common abnormalities in the processes within the kidney tubules that regulate both the reabsorption of salt and the excretion of acid may result in concomitant high blood pressure and increased protein loss in the kidney. Thus the overall aim of the project is to investigate the interrelationship between protein reabsorption and catabolism and Na+ reabsorption in the human kidney tubule. The project uses the combined methods of cultured human kidney tubules, biochemical and molecular biology techniques which are unavailable in other laboratories in Australia (and internationally). This project will comprehensively characterise the mechanisms of protein uptake and salt reabsorption in human kidney tubule cells when exposed to both normal and high concentrations of protein. The exact nature of the interaction of protein uptake with salt reabsorption and hence high blood pressure will be determined. As both hypertension and persistent proteinuria are the most important predictors of tubulointerstitial pathology and progressive decline in renal function in almost all renal disease, the understanding of the precise interaction between these two factors is essential in the design of renoprotective therapies.

尿中蛋白质丢失和盐潴留之间的临床关联，导致高血压和肾功能的进行性下降，是众所周知的。在正常情况下，肾脏每天过滤180升水并重吸收1.7公斤盐，这一功能主要由肾脏中的肾小管执行。类似地，肾小管细胞每天重吸收并分解多达3克的白蛋白。过去，人们认为尿液中蛋白质损失过多主要是由于肾脏过滤单元的问题，而不是由于肾小管中蛋白质重吸收异常。然而，我们认为肾小管内调节盐重吸收和酸排泄过程的常见异常可能导致伴随的高血压和肾脏蛋白质丢失增加。因此，该项目的总体目标是研究蛋白质重吸收与人肾小管中的钙离子和Na+重吸收之间的相互关系。该项目采用培养人肾小管、生物化学和分子生物学技术的综合方法，这是澳大利亚（和国际）其他实验室无法提供的。本项目将全面研究正常和高浓度蛋白质暴露时人肾小管细胞蛋白质摄取和盐重吸收的机制。蛋白质吸收与盐重吸收相互作用的确切性质，因此高血压将被确定。由于高血压和持续性蛋白尿是几乎所有肾脏疾病中肾小管间质病理和肾功能进行性下降的最重要预测因素，因此了解这两个因素之间的确切相互作用对于设计肾脏保护治疗至关重要。