Urinary N-acetylglucosaminidase in People Environmentally Exposed to Cadmium Is Minimally Related to Cadmium-Induced Nephron Destruction

Exposure to even low levels of the environmental pollutant cadmium (Cd) increases the risk of kidney damage and malfunction. The body burden of Cd at which these outcomes occur is not, however, reliably defined. Here, multiple-regression and mediation analyses were applied to data from 737 non-diabetic Thai nationals, of which 9.1% had an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m² (a low eGFR). The excretion of Cd (E_Cd), and renal-effect biomarkers, namely β₂-microglobulin (E_β2M), albumin (E_alb), and N-acetylglucosaminidase (E_NAG), were normalized to creatinine clearance (C_cr) as E_Cd/C_cr E_β2M/C_cr, E_alb/C_cr, and E_NAG/C_cr. After adjustment for potential confounders, the risks of having a low eGFR and albuminuria rose twofold per doubling E_Cd/C_cr rates and they both varied directly with the severity of β₂-microglobulinuria. Doubling E_Cd/C_cr rates also increased the risk of having a severe tubular injury, evident from E_NAG/C_cr increments [POR = 4.80, <i>p</i> = 0.015]. E_NAG/C_cr was strongly associated with E_Cd/C_cr in both men (β = 0.447) and women (β = 0.394), while showing a moderate inverse association with eGFR only in women (β = -0.178). A moderate association of E_NAG/C_cr and E_Cd/C_cr was found in the low- (β = 0.287), and the high-Cd body burden groups (β = 0.145), but E_NAG/C_cr was inversely associated with eGFR only in the high-Cd body burden group (β = -0.223). These discrepancies together with mediation analysis suggest that Cd-induced nephron destruction, which reduces GFR and the tubular release of NAG by Cd, involves different mechanisms and kinetics.