Pathogenic Mechanisms In Inflammatory Demyelinating Neuropathies
Funder
National Health and Medical Research Council
Funding Amount
$378,750.00
Summary
The causes and disease mechanisms of inflammatory neuropathy remain mostly unknown. Although treatments have been developed (intravenous immunoglobulin and plasma exchange) they are extremely expensive, non-specific in action, beyond the means of the worlds most populous nations and a considerable burden to health resources in developed nations. These studies aim to understand better the mechanism of disease production so that better and more affordable therapy can be developed. In our current g ....The causes and disease mechanisms of inflammatory neuropathy remain mostly unknown. Although treatments have been developed (intravenous immunoglobulin and plasma exchange) they are extremely expensive, non-specific in action, beyond the means of the worlds most populous nations and a considerable burden to health resources in developed nations. These studies aim to understand better the mechanism of disease production so that better and more affordable therapy can be developed. In our current grant we have made a most important breakthrough - which is that antibodies to a major structural protein of the myelin sheath are responsible for disease production in one subgroup of patients. We plan to search for other antigenic targets in other patient groups and to see whether we can regulate the disease by new mechanisms which would be cheaper and more effective.Read moreRead less
Molecular Mechanisms Linking Proteinuria And Sodium Retention
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
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 pro ....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.Read moreRead less