Renal dysfunction induced by cadmium: biomarkers of critical effects.

Cadmium (Cd) is cumulative poison which can damage the kidneys after prolonged exposure in the industry or the environment. Renal damage induced by Cd affects primarily the cellular and functional integrity of the proximal tubules, the main site of the renal accumulation of the metal. This results in a variety of urinary abnormalities including an increased excretion of calcium, amino acids, enzymes and proteins. These effects have been documented by a large number of studies conducted during more than two decades in experimental animals and in populations environmentally or occupationally exposed to Cd. There is now a general agreement to say that the most sensitive and specific indicator of Cd-induced renal dysfunction is a decreased tubular reabsorption of low molecular weight proteins, leading to the so-called tubular proteinuria. beta2-microblobulin, retinol-binding protein and alpha1-microglobulin are the microproteins the most commonly used for screening renal damage in populations at risk. Tubular dysfunction develops in a dose-dependent manner according to the internal dose of Cd as assessed on the basis of Cd levels in kidney, urine or in blood. Depending on the sensitivity of the renal biomarker and the susceptibility of the exposed populations, the thresholds of urinary Cd vary from 2 to 10 microg/g creatinine. The thresholds associated with the development of the microproteinuria, the critical effect predictive of a decline of the renal function, is estimated around 10 microg/g creatinine for both occupationally and environmentally exposed populations. Much lower thresholds have been reported in some European studies conducted on the general population. These low thresholds, however, have been derived from associations whose causality remains uncertain and for urinary protein increases that might be reversible. Cd-induced microproteinuria is usually considered as irreversible except at the incipient stage of the intoxication where a partial or complete reversibility has been found in some studies.