Molecular mechanisms linking proteinuria and sodium retention

尿中蛋白质丢失与盐潴留之间的临床关联，导致高血压和肾功能进行性下降，这是众所周知的。在正常情况下，肾脏每天过滤180公升的水，并重新吸收1.7公斤的盐。这些功能主要是由肾脏的肾小管完成的。同样，肾小管细胞每天重吸收和分解高达3克的白蛋白。过去，人们一直认为，尿液中蛋白质的过多损失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的异常。然而，我们认为在肾小管中调节盐的重吸收和酸的排泄的过程中常见的异常可能导致伴随的高血压和肾脏中增加的蛋白质损失。因此，该项目的总体目标是研究人体肾小管中蛋白质重吸收与分解代谢和Na+重吸收之间的相互关系。该项目采用培养人肾小管、生化和分子生物学技术相结合的方法，这是澳大利亚（和国际）其他实验室无法获得的。该项目将全面表征人体肾小管细胞在暴露于正常和高浓度蛋白质时蛋白质摄取和盐重吸收的机制。蛋白质摄取与盐重吸收相互作用的确切性质将被确定。在几乎所有肾脏疾病中，高血压和持续性蛋白尿都是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保护疗法至关重要。

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.