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Erroneous conclusions may result from normalization of urine cadmium and N-acetyl-β-D-glucosaminidase concentrations ([Cd] u and [NAG] u ) to the urine creatinine concentration ([cr] u ). In theory, the sources of these errors are nullified by normalization of excretion rates (E Cd and E NAG ) to creatinine clearance (C cr ). We hypothesized that this alternate approach would clarify the contribution of Cd-induced tubular injury to nephron loss. We studied 931 Thai subjects with a wide range of environmental Cd exposure. For x = Cd or NAG, E  x  /E cr and E  x  /C cr were calculated as [ x ] u /[cr] u and [ x ] u [cr] p /[cr] u , respectively. Glomerular filtration rate (GFR) was estimated according to the Chronic Kidney Disease (CKD) Epidemiology Collaboration (eGFR), and CKD was defined as eGFR &lt; 60 mL/min/1.73m 2 . In multivariable logistic regression analyses, prevalence odds ratios (PORs) for CKD were higher for log(E Cd /C cr ) and log(E NAG /C cr ) than for log(E Cd /E cr ) and log(E NAG /E cr ). Doubling of E Cd /C cr and E NAG /C cr increased POR by 132% and 168%; doubling of E Cd /E cr and E NAG /E cr increased POR by 64% and 54%. As log(E Cd /C cr ) rose, associations of eGFR with log(E Cd /C cr ) and log(E NAG /C cr ) became stronger, while associations of eGFR with log(E Cd /E cr ) and log(E NAG /E cr ) became insignificant. In univariate regressions of eGFR on each of these logarithmic variables, R 2 was consistently higher with normalization to C cr . Our tabular and graphic analyses uniformly indicate that normalization to C cr clarified relationships of E Cd and E NAG to eGFR.

The Effect of Cadmium on GFR Is Clarified by Normalization of Excretion Rates to Creatinine Clearance