Abstract
In theory, the identification of the source of excreted cadmium (Cd) might elucidate the pathogenesis of Cd-induced chronic kidney disease (CKD). With that possibility in mind, we studied Thai subjects with low, moderate, and high Cd exposure. We measured urine concentrations of Cd, ([Cd](u)); N-acetyl-β-d-glucosaminidase, a marker of cellular damage ([NAG](u)); and β(2)-microglobulin, an indicator of reabsorptive dysfunction ([β(2)MG](u)). To relate excretion rates of these substances to existing nephron mass, we normalized the rates to creatinine clearance, an approximation of the glomerular filtration rate (GFR) (E(Cd)/C(cr), E(NAG)/C(cr), and E(β2MG)/C(cr)). To link the loss of intact nephrons to Cd-induced tubular injury, we examined linear and quadratic regressions of estimated GFR (eGFR) on E(Cd)/C(cr), eGFR on E(NAG)/C(cr), and E(NAG)/C(cr) on E(Cd)/C(cr). Estimated GFR varied inversely with both ratios, and E(NAG)/C(cr) varied directly with E(Cd)/C(cr). Linear and quadratic regressions of E(β2MG)/C(cr) on E(Cd)/C(cr) and E(NAG)/C(cr) were significant in moderate and high Cd-exposure groups. The association of E(NAG)/C(cr) with E(Cd)/C(cr) implies that both ratios depicted cellular damage per surviving nephron. Consequently, we infer that excreted Cd emanated from injured tubular cells, and we attribute the reduction of eGFR to the injury. We suggest that E(Cd)/C(cr), E(NAG)/C(cr), and eGFR were associated with one another because each parameter was determined by the tubular burden of Cd.