The role of trace elements in uraemic toxicity

Although most research on uraemic toxicity has focused on the retention or removal of organic solutes, subtle changes in the concentration of inorganic compounds are also of importance because these compounds may have significant clinical consequences. Potential clinical implications include increased risk of cancer, cardiovascular disease, immune deficiency, anaemia, renal function impairment and bone disease. In uraemic patients, the most important factor affecting trace element concentration is the degree of renal failure and modality of renal replacement therapy. Accumulation of trace elements in haemodialysis patients has resulted from dialysate contaminated with aluminium and strontium. Several trace elements have been implicated in the decline of renal function. These include arsenic, cadmium, copper, germanium, lead and mercury. In uraemic patients, aluminium, cadmium, chromium, lanthanum, strontium and zinc have been shown to accumulate in bone. In addition to substantial evidence linking aluminium to renal osteodystrophy, studies have also implicated cadmium, iron and strontium in bone disease. Studies using a rat model of chronic renal failure have demonstrated an association between lanthanum accumulation and mineralization defects characteristic of osteomalacia. Investigations of arsenic accumulation in animal models have demonstrated that speciation of trace elements potentially may alter toxicities of trace elements accumulated in uraemic patients. Conversely, the presence of uraemic toxins may also alter the uptake and toxicity of certain trace elements. Although research in uraemic patients has focused primarily on total concentrations of trace elements, the evolution of both inorganic and organic species should be considered separately.