Characterization of the proteinuria induced by prolonged oral administration of cadmium in female rats

Abstract

Female Sprague-Dawley rats were given 200 ppm cadmium (Cd) in the drinking water for 11 months. Total proteinuria and the concentrations of Cd in blood, urine, liver and kidney cortex were determined monthly. The proteinuria was characterized by Sephadex G-75 chromatography and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. From the 8th month of treatment, the Cd concentration in the kidney cortex levels off at a value of about 250 microgram/g wet wt and this phenomenon coincides with the occurrence of proteinuria. The proteinuria was characterized by an increased urinary excretion of high molecular weight (HMW) proteins, particularly gamma-globulins. Aminoaciduria also increased which suggests the existence of a slight tubular dysfunction. The renal dysfunction induced by chronic oral administration of Cd seems different from that observed in a previous study in which Cd was administered by the i.p. route (1 mg Cd/kg, 5 times a week for 2 months). For the same level of Cd in the kidney cortex the proteinuria induced by i.p. injection of Cd was usually of mixed type and in some cases of the tubular type. The development of this proteinuria was coincident with the levelling off of Cd concentration in the kidney cortex and in the liver. The saturation of liver by Cd is very likely at the origin of he extensive tubular lesion and of the mixed type proteinuria observed in the i.p. experiment. These results demonstrate the importance of mode of Cd administration on the nature of the Cd-induced proteinuria in animal. They support also our proposal that both low and HMW proteins should be determined in urine for the early detection of renal damage occurring in man chronically exposed to cadmium.