Cadmium: The importance of this non-essential trace metal in urology

This work gives an insight into the damaging effects which cadmium produces in terms of altered calcium metabolism resulting specifically in a steady rise in the prevalence of renal stone disease in a group of workers who were monitored annually from 1975 to 1982. The men in question were very heavily exposed to cadmium and when compared to a reference population it can be seen that the mean levels of blood cadmium in the group were always at least five times greater than the normal population. By careful annual follow up it was also possible to show that despite a complete and instant cessation of exposure to the metal the blood cadmium levels, like the urine cadmium levels did not immediately return to normal but remained constantly elevated. At the levels of exposure this must indicate a very large body burden of cadmium and what is more, despite the large amounts being lost by excretion in the urine, a mobilisation of cadmium must be taking place from large deposits in bones and other sites. In order to assess the significance of the biochemical parameters found in the group under study, it was necessary to look at a variety of different groups of workers who were involved in different occupations within the factory under particular study or who were involved in different cadmium processes in a variety of different factories. The study of these different groups has enabled me to examine the different biochemical parameters across a wide spectrum of workers and has resulted in the clear demonstration that the workers in the principal study group had clearly been the most seriously affected with respect to exposure to cadmium. It has also been possible to demonstrate that workers beyond the immediate location of cadmium exposure appear to have a greater than normal risk of having higher blood cadmium levels than normal subjects and also a greater likelihood of having damaged cells as a potential nucleus for renal stone formation. When such foci are present and are combined with altered calcium and phosphate excretion then it should be less than surprising to discover that stone formation is a major effect of chronic cadmium poisoning. Because of the random population survey which had been undertaken by myself along with other helpers it was possible to demonstrate that the prevalence of stone disease in this area is 3.5%. At the initial examination of the coppersmiths in 1975 it was immediately obvious that the prevalence of stone disease in the group was 18.5% - a figure which is comparable to other reports. It is surprising therefore that there does not seem to be any follow up by those other workers specifically to discover whether or not the rate of stone disease remains the same or as has been found in the present study steadily increases with time. In the coppersmiths group in 1982 the prevalence of stone disease reached over 40%. Interestingly the subjects most likely to develop stone disease were those who initially were found to have subnormal or low normal serum inorganic phosphate values. Apart from the clinical problems of stone disease, the presence of an unexplained and persistent hyper-calciuria is highly significant to the long term welfare of the individual. In rather specialized circumstances in Japan it has been demonstrated in post menopausal women in whom the effects of repeated pregancies have already presumably reduced skeletal calcium that excess cadmium can result in a severe osteo malacia described as itai-itai disease. Although our studies have not found such severe skeletal effects nevertheless there is evidence that a whole body deficiency of calcium does occur in the workers examined as evidenced by the in vivo neutron activation study. It is therefore considered essential that in the general assessment of possible metabolic abnormalities likely to be found in the examination of a stone subject the demonstration of idiopathic hyper-calciuria should alert the examiner to the possibility that a cause for the hypercalciuria could be chronic cadmium exposure. The latter can be excluded by a careful industrial history together with measurements of blood and urine cadmium along with estimations of serum calcium, inorganic phosphate and urinary protein estimations