Urinary Cadmium Threshold to Prevent Kidney Disease Development

Abstract

The frequently observed association between kidney toxicity and long-term cadmium (Cd) exposure has long been dismissed and deemed not to be of clinical relevance. However, Cd exposure has now been associated with increased risk of developing chronic kidney disease (CKD). We investigated the link that may exist between kidney Cd toxicity markers and clinical kidney function measure such as estimated glomerular filtration rates (eGFR). We analyzed data from 193 men to 202 women, aged 16&minus;87 years [mean age 48.8 years], who lived in a low- and high-Cd exposure areas in Thailand. The mean (range) urinary Cd level was 5.93 (0.05⁻57) &mu;g/g creatinine. The mean (range) for estimated GFR was 86.9 (19.6&minus;137.8) mL/min/1.73 m². Kidney pathology reflected by urinary &beta;2-microglobulin (&beta;2-MG) levels &ge; 300 &mu;g/g creatinine showed an association with 5.32-fold increase in prevalence odds of CKD (p = 0.001), while urinary Cd levels showed an association with a 2.98-fold greater odds of CKD prevalence (p = 0.037). In non-smoking women, Cd in the highest urinary Cd quartile was associated with 18.3 mL/min/1.73 m² lower eGFR value, compared to the lowest quartile (p < 0.001). Evidence for Cd-induced kidney pathology could thus be linked to GFR reduction, and CKD development in Cd-exposed people. These findings may help prioritize efforts to reassess Cd exposure and its impact on population health, given the rising prevalence of CKD globally.

Keywords: N-acetyl-β-d-glucosaminidase; cadmium; chronic kidney disease; clinical kidney function measure; estimated glomerular filtration rate; population health; toxicity threshold limit; tubular dysfunction; urine protein; β2-microglobulin.

Figure 1

Cadmium-dose dependent reduction in glomerular filtration rates in non-smoking women. Bars represent mean eGFR ± SE values for groups of subjects stratified according to the quartiles of urinary Cd excretion levels. Urinary Cd levels in quartiles 1, 2, 3 and 4 are 0.05–0.50, 0.51–2.95, 2.96–8.80, 8.81–57.57 μg/g creatinine, and the corresponding numbers of subjects are 100, 101, 97 and 97, respectively. The mean eGFR values are adjusted for interactions and covariates as follows; age 48.79 years, BMI 22.21 kg/m², urinary β2-MG 59.74 μg/g creatinine, NAG 4.29 units/g creatinine, and protein excretion 24.98 mg/g creatinine. p values ≤ 0.05 indicate statistically significant difference between adjusted mean eGFR in quartile 2, 3 and 4, compared with the urinary Cd quartile 1.

Figure 2

Scatterplots of kidney function measure vs. tubular dysfunction biomarker. The regression lines of eGFR vs. urinary β2-MG levels are shown for groups of subjects according to smoking status (A) and urinary Cd quartiles (B). The reference line in (A) is based on the CKD diagnosis, eGFR < 60 mL/min/1.73 m². The R² values and the β coefficients shown in (A,B) are unadjusted. Urinary Cd levels in quartiles 1, 2, 3 and 4 are 0.05–0.50, 0.51–2.95, 2.96–8.80, and 8.81–57.57 μg/g creatinine, and the corresponding numbers of subjects are 100, 101, 97 and 97, respectively.

Figure 3

Scatterplots of kidney function measure vs. tubular injury biomarker. The regression lines of eGFR vs. urinary NAG levels are shown for groups of subjects according to smoking status (A) and urinary Cd quartiles (B). The reference line in (A) is based on the CKD diagnosis, eGFR < 60 mL/min/1.73 m². The R² values the β coefficients shown in (A,B) are unadjusted. Urinary Cd levels in quartiles 1, 2, 3 and 4 are 0.05–0.50, 0.51–2.95, 2.96–8.80, and 8.81–57.57 μg/g creatinine, and the corresponding numbers of subjects are 100, 101, 97 and 97, respectively.

Figure 4

Scatterplots of kidney function measure vs. glomerular damage biomarker. The regression lines of eGFR vs. urinary protein levels are shown for subjects stratified according to smoking status (A) and urinary Cd quartiles (B). The reference line in (A) is based on the CKD diagnosis, eGFR < 60 mL/min/1.73 m². The R² values and the β coefficients shown in (A,B) are unadjusted. Urinary Cd levels in quartiles 1, 2, 3 and 4 are 0.05–0.50, 0.51–2.95, 2.96–8.80, and 8.81–57.57 μg/g creatinine, and the corresponding numbers of subjects are 100, 101, 97 and 97, respectively.