Effect of toxins on the mammal kidney: study of the kidney function through luminal perfusion of isolated proximal tubules.

By Koen Jolling 

Cadmium is among others a heavy metal that is known to be an environmental contaminant with proven toxicity for humans and animals.  Its distribution in the environment is the result of natural processes and anthropogenic activities. The latter include industrial (non-ferrous metal production, combustion of fossil fuel) and agricultural (phosphate fertilizers, deposition of manure and sewage sludge to agricultural land) activities. In humans, cadmium exposure occurs by means of ingestion of polluted food and drinking water or through inhalation of cadmium-dust (e.g. smoking), leading to an accumulation of cadmium in different tissues. Exposure to cadmium results in a variety of acute and chronic toxic effects depending on the dose, the route of entry and the form in which cadmium is taken up.  The liver, kidney, lungs and small intestine are the main target organs of cadmium accumulation.  In the kidneys, it is well documented that cadmium induces among others nephropathy, characterized by abnormalities in renal tubule reabsorption.  This abnormal tubular reabsorption primarily reflects defects in proximal tubule transport resembling those seen in Fanconi's syndrome (e.g. glucosuria, proteinuria, aminoaciduria, etc.). 

The aim of this research project is to better characterize the cadmium induced nephrotoxicity with respect to the electrophysiological properties of the proximal tubule using the luminal perfusion technique. The first goal is to establish a simple method for obtaining isolated mouse proximal tubules that are functionally and morphologically intact. The second objective is to characterize the electrophysiological properties of these isolated proximal tubules under control conditions and after acute or chronic exposure to cadmium (CdCl₂, Cd-Methallothionein). The final goal is to explore the electrophysiological properties of proximal tubules isolated from mice exposed to real cadmium concentrations. Furthermore, these findings will be linked to results obtained from an in vivo model.  In vivo, mice will be exposed acutely as well as chronically to Cadmium followed by an assessment of overall health and an evaluation of renal function of the exposed animal.