Full validation of biomarkers should rely on follow-up studies indicating the health significance of observed changes. Microalbuminuria and low-molecular weight proteinuria fulfil this condition in subjects suffering from diabetes mellitus and from chronic cadmium poisoning, respectively. In such situations, both markers are predictors of an accelerated deterioration of renal function. Outside of these two situations, no information is available to interpret the early changes resulting from chemical exposure and there is a need to conduct longitudinal studies on populations with well-characterized exposure or risk. However, it has been noted that, perhaps with the exception of chemicals with a very long half-life, the long-term significance of early changes is very difficult to assess (Mutti, 1995). Therefore, when persistent microproteinuria is observed in the context of a documented chronic exposure to a suspected or established nephrotoxicant, it is prudent to consider that it might have a similar meaning as in incipient diabetic or cadmium nephropathy (Bernard et al., 1979).


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