Heavy metal imaging in fibrotic human kidney tissue using the synchrotron X-ray fluorescence microprobe

Abnormally high exposure to heavy metals and their accumulation in some tissues are recognized as causes of many acute and chronic human diseases. Because of the roles many metals have in normal human physiology, proving cause and effect between exposure to heavy metals and pathogenesis of disease is problematic. Therefore, many illnesses that develop through occupational and environmental exposure are not considered directly related to heavy metal toxicity. The high sensitivity and spatial resolution of elements using the synchrotron X-ray fluorescence microprobe (XFM) may give a robust means to investigate spatial distribution of heavy metals in correlation with specific pathologies. For example, proven presence of different heavy metals may correlate spatially with kidney fibrosis, suggesting a mechanistic link between heavy metal-induced fibrosis and chronic kidney disease. One specific example that may benefit from such an analysis relates to a cluster of people with chronic kidney disease of unknown cause (CKDu), in a significant proportion of the population of the North Central Province of Sri Lanka. Here, it was postulated that heavy metal exposure, in particular of cadmium, in foods and agriculture may be one cause of end-stage kidney disease and premature death of patients with CKDu. Synchrotron methods had not been applied previously to this particular problem. This manuscript provides a brief review of the literature and reports some pilot data from an investigation of localization of kidney fibrosis in CKDu with selected heavy metals including cadmium.