Chronic exposure to cadmium is associated with a marked reduction in glomerular filtration rate

Satarug, Soisungwan; Boonprasert, Kanyarat; Gobé, Glenda C.; Ruenweerayut, Ronnatrai; Johnson, David W.; Na‐Bangchang, Kesara; Vesey, David A.

doi:10.1093/ckj/sfy113

Cited by 32 publications

(27 citation statements)

References 31 publications

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“…It is increasingly recognized that creatinine adjustment is problematic, and urine specific gravity has been used to correct for dilution effects [9,44,45,[50][51][52]. Herein, we have demonstrated the utility of normalizing excretion rate of metals to creatinine clearance that only required simultaneous urine and blood sampling together with the equations, given in Section 2.3 [33,35].…”

Section: Discussionmentioning

confidence: 99%

“…Elevated dietary Cd intake has been associated with an increased risk of CKD in China [30]. A marked decrease in the GFR has also been observed in residents of an area with Cd pollution in Thailand [2,[31][32][33][34][35], as well as in Cd-exposed workers [36,37]. Likewise, marked GFR decreases have been noted in workers and residents of Pb-smelter communities [38].…”

Section: Introductionmentioning

confidence: 99%

“…However, a cross-sectional analysis of data from adolescents (n = 2709, aged 12-19 years) who were enrolled in NHANES 2009-2014 reported positive associations of urinary Cd and Pb with an increased eGFR and BUN in models that incorporated urinary creatinine as a covariate [42]. A common practice of normalizing urinary concentrations of Cd to urinary concentrations of creatinine may have caused these disparate findings [33,35,44,45].…”

Section: Introductionmentioning

confidence: 99%

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A Comparison of the Nephrotoxicity of Low Doses of Cadmium and Lead

Satarug

Gobé

Ujjin

et al. 2020

Toxics

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Environmental exposure to moderate-to-high levels of cadmium (Cd) and lead (Pb) is associated with nephrotoxicity. In comparison, the health impacts of chronic low-level exposure to Cd and Pb remain controversial. The aim of this study was to therefore evaluate kidney dysfunction associated with chronic low-level exposure to Cd and Pb in a population of residents in Bangkok, Thailand. The mean age and the estimated glomerular filtration rate (eGFR) for 392 participants (195 men and 197 women) were 34.9 years and 104 mL/min/1.73 m2, respectively, while the geometric mean concentrations of urinary Cd and Pb were 0.25 μg/L (0.45 μg/g of creatinine) and 0.89 μg/L (1.52 μg/g of creatinine), respectively. In a multivariable regression analysis, the eGFR varied inversely with blood urea nitrogen in both men (β = −0.125, p = 0.044) and women (β = −0.170, p = 0.008), while inverse associations of the eGFR with urinary Cd (β = −0.132, p = 0.043) and urinary Pb (β = −0.130, p = 0.044) were seen only in women. An increased urinary level of Cd to the median level of 0.38 μg/L (0.44 μg/g of creatinine) was associated with a decrease in the eGFR by 4.94 mL/min/1.73 m2 (p = 0.011). The prevalence odds of a reduced eGFR rose 2.5-, 2.9- and 2.3-fold in the urinary Cd quartile 3 (p = 0.013), the urinary Cd quartile 4 (p = 0.008), and the urinary Pb quartile 4 (p = 0.039), respectively. This study suggests that chronic exposure to low-level Cd is associated with a decline in kidney function and that women may be more susceptible than men to nephrotoxicity due to an elevated intake of Cd and Pb.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Comparison of the Nephrotoxicity of Low Doses of Cadmium and Lead

Satarug

Gobé

Ujjin

et al. 2020

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“…In the present study, we have continued the recently introduced practice of normalizing excretion of Cd, NAG, and β 2 MG to creatinine clearance instead of creatinine excretion [26]. Because the resulting ratios express E Cd , E NAG , and E β2MG as functions of intact nephron mass, they nullify sources of imprecision that accompany normalization to E cr or [cr] u .…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, a fraction of Cd remains unbound to MT and is presumed to promote autophagy, apoptosis, and necrosis as accumulation of Cd progresses [19,21]. Manifestations of renal toxicity include increased excretion of cellular proteins, impaired reabsorption of filtered substances, histologically demonstrable tissue injury, loss of intact nephrons, and reduction of the glomerular filtration rate (GFR) [5,8,[21][22][23][24][25][26][27]. GFR may continue to fall for many years after exogenous exposure ceases [22,24], presumably because traffic of CdMT from the liver to kidneys persists.…”

Section: Introductionmentioning

confidence: 99%

The Source and Pathophysiologic Significance of Excreted Cadmium

Satarug

Vesey

Ruangyuttikarn

et al. 2019

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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 β2-microglobulin, an indicator of reabsorptive dysfunction ([β2MG]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) (ECd/Ccr, ENAG/Ccr, and Eβ2MG/Ccr). To link the loss of intact nephrons to Cd-induced tubular injury, we examined linear and quadratic regressions of estimated GFR (eGFR) on ECd/Ccr, eGFR on ENAG/Ccr, and ENAG/Ccr on ECd/Ccr. Estimated GFR varied inversely with both ratios, and ENAG/Ccr varied directly with ECd/Ccr. Linear and quadratic regressions of Eβ2MG/Ccr on ECd/Ccr and ENAG/Ccr were significant in moderate and high Cd-exposure groups. The association of ENAG/Ccr with ECd/Ccr 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 ECd/Ccr, ENAG/Ccr, and eGFR were associated with one another because each parameter was determined by the tubular burden of Cd.

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