EARLY MARKERS OF CADMIUM NEPHROTOXICITY - BIOLOGICAL SIGNIFICANCE AND PREDICTIVE VALUE

One of the earliest manifestations of cadmium (Cd) nephrotoxicity is an increased urinary excretion (UE) of low or high molecular weight (Mr) proteins. The increased UE of low Mr proteins (e.g. /?2-microgIobulin, o^-microglobulin, retinol-binding protein results from damage to the proximal tubule in which Cd selectivity accumulates. The enhanced UE of high Mr proteins (e.g. albumin, transferrin, IgG) results partly from an increased glomerular permeability probably due to a loss of the glomerular polyanion which is reflected by a parallel reduction of red blood cell membrane negative charges. The interference of Cd with the glomerular structure is also suggested by the occurrence of anti-GBM antibodies and by a decreased mesangial uptake of macromolecules. Cd proteinuria may be accompanied by an increased UE of glycosaminoglycans, enzymes, tubular antigens, aminoacids, glucose or Tamm—Horsfall glycoprotein. A recent prospective study indicates that the appearance of a persistent low or high Mr proteinuria in Cd workers is the forerunner sign of a progressive deterioration of the renal function. The predictive value of other renal disturbances induced by Cd (e.g. decreased RBC charges) remains to be established. The critical concentrations of Cd in urine and renal cortex for the development of microproteinuria in male workers (10% response rate) are estimated at 10/zg/g creatinine and 200 ppm, respectively. The question which now arises is whether these critical levels are also applicable to the general population and to other renal effects induced by Cd (e.g. decrease of glomerular polyanion). © 1990, Taylor & Francis Group, LLC. All rights reserved.