Limits...
Benchmark Dose for Urinary Cadmium based on a Marker of Renal Dysfunction: A Meta-Analysis.

Woo HD, Chiu WA, Jo S, Kim J - PLoS ONE (2015)

Bottom Line: Low doses of cadmium can cause adverse health effects.Meta-regression analysis showed that a significant predictor of BMD was the cut-off point which denotes an abnormal level.The BMD was significantly associated with the cut-off point defining the abnormal level of renal dysfunction markers.

View Article: PubMed Central - PubMed

Affiliation: Molecular Epidemiology Branch, National Cancer Center, Goyang-si, Korea.

ABSTRACT

Background: Low doses of cadmium can cause adverse health effects. Benchmark dose (BMD) and the one-sided 95% lower confidence limit of BMD (BMDL) to derive points of departure for urinary cadmium exposure have been estimated in several previous studies, but the methods to derive BMD and the estimated BMDs differ.

Objectives: We aimed to find the associated factors that affect BMD calculation in the general population, and to estimate the summary BMD for urinary cadmium using reported BMDs.

Methods: A meta-regression was performed and the pooled BMD/BMDL was estimated using studies reporting a BMD and BMDL, weighted by sample size, that were calculated from individual data based on markers of renal dysfunction.

Results: BMDs were highly heterogeneous across studies. Meta-regression analysis showed that a significant predictor of BMD was the cut-off point which denotes an abnormal level. Using the 95th percentile as a cut off, BMD5/BMDL5 estimates for 5% benchmark responses (BMR) of β2-microglobulinuria (β2-MG) estimated was 6.18/4.88 μg/g creatinine in conventional quantal analysis and 3.56/3.13 μg/g creatinine in the hybrid approach, and BMD5/BMDL5 estimates for 5% BMR of N-acetyl-β-d-glucosaminidase (NAG) was 10.31/7.61 μg/g creatinine in quantal analysis and 3.21/2.24 g/g creatinine in the hybrid approach. However, the meta-regression showed that BMD and BMDL were significantly associated with the cut-off point, but BMD calculation method did not significantly affect the results. The urinary cadmium BMDL5 of β2-MG was 1.9 μg/g creatinine in the lowest cut-off point group.

Conclusion: The BMD was significantly associated with the cut-off point defining the abnormal level of renal dysfunction markers.

No MeSH data available.


Related in: MedlinePlus

The relationship between cut-off point for adverse effect and urinary BMD for β2-MG.BMDS (▲): BMD calculated by EPA BMDS software, Hybrid (○): BMD calculated by hybrid approach. The positive relationships between cut-off point of β2-MG and BMD in both conventional quantal analysis and the hybrid approach were observed.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4430293&req=5

pone.0126680.g002: The relationship between cut-off point for adverse effect and urinary BMD for β2-MG.BMDS (▲): BMD calculated by EPA BMDS software, Hybrid (○): BMD calculated by hybrid approach. The positive relationships between cut-off point of β2-MG and BMD in both conventional quantal analysis and the hybrid approach were observed.

Mentions: Meta-regression analyses were conducted to identify the cause of the heterogeneity across the studies (Table 3). The urinary cadmium level, the cut-off point (as a continuous variable), BMD calculation method (hybrid vs. quantal model), and sex (total and male subjects vs. female subjects) were used in the meta-regression. The meta-regression for BMD of β2-MG showed that the BMD5 and BMD10 were significantly associated with the cut-off point, but BMD calculation method did not significantly affect the results. BMDs for β2-MG were mostly calculated using log-logistic model among conventional quantal analysis. BMD model (probit, quantal linear, logistic vs. log-logistic) was added in the meta-regression, but only cut-off point was significantly associated with BMD for β2-MG (data not shown). The obvious relationships between cut-off point of β2-MG and BMD in both conventional quantal analysis and the hybrid approach were observed (Fig 2).


Benchmark Dose for Urinary Cadmium based on a Marker of Renal Dysfunction: A Meta-Analysis.

Woo HD, Chiu WA, Jo S, Kim J - PLoS ONE (2015)

The relationship between cut-off point for adverse effect and urinary BMD for β2-MG.BMDS (▲): BMD calculated by EPA BMDS software, Hybrid (○): BMD calculated by hybrid approach. The positive relationships between cut-off point of β2-MG and BMD in both conventional quantal analysis and the hybrid approach were observed.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4430293&req=5

pone.0126680.g002: The relationship between cut-off point for adverse effect and urinary BMD for β2-MG.BMDS (▲): BMD calculated by EPA BMDS software, Hybrid (○): BMD calculated by hybrid approach. The positive relationships between cut-off point of β2-MG and BMD in both conventional quantal analysis and the hybrid approach were observed.
Mentions: Meta-regression analyses were conducted to identify the cause of the heterogeneity across the studies (Table 3). The urinary cadmium level, the cut-off point (as a continuous variable), BMD calculation method (hybrid vs. quantal model), and sex (total and male subjects vs. female subjects) were used in the meta-regression. The meta-regression for BMD of β2-MG showed that the BMD5 and BMD10 were significantly associated with the cut-off point, but BMD calculation method did not significantly affect the results. BMDs for β2-MG were mostly calculated using log-logistic model among conventional quantal analysis. BMD model (probit, quantal linear, logistic vs. log-logistic) was added in the meta-regression, but only cut-off point was significantly associated with BMD for β2-MG (data not shown). The obvious relationships between cut-off point of β2-MG and BMD in both conventional quantal analysis and the hybrid approach were observed (Fig 2).

Bottom Line: Low doses of cadmium can cause adverse health effects.Meta-regression analysis showed that a significant predictor of BMD was the cut-off point which denotes an abnormal level.The BMD was significantly associated with the cut-off point defining the abnormal level of renal dysfunction markers.

View Article: PubMed Central - PubMed

Affiliation: Molecular Epidemiology Branch, National Cancer Center, Goyang-si, Korea.

ABSTRACT

Background: Low doses of cadmium can cause adverse health effects. Benchmark dose (BMD) and the one-sided 95% lower confidence limit of BMD (BMDL) to derive points of departure for urinary cadmium exposure have been estimated in several previous studies, but the methods to derive BMD and the estimated BMDs differ.

Objectives: We aimed to find the associated factors that affect BMD calculation in the general population, and to estimate the summary BMD for urinary cadmium using reported BMDs.

Methods: A meta-regression was performed and the pooled BMD/BMDL was estimated using studies reporting a BMD and BMDL, weighted by sample size, that were calculated from individual data based on markers of renal dysfunction.

Results: BMDs were highly heterogeneous across studies. Meta-regression analysis showed that a significant predictor of BMD was the cut-off point which denotes an abnormal level. Using the 95th percentile as a cut off, BMD5/BMDL5 estimates for 5% benchmark responses (BMR) of β2-microglobulinuria (β2-MG) estimated was 6.18/4.88 μg/g creatinine in conventional quantal analysis and 3.56/3.13 μg/g creatinine in the hybrid approach, and BMD5/BMDL5 estimates for 5% BMR of N-acetyl-β-d-glucosaminidase (NAG) was 10.31/7.61 μg/g creatinine in quantal analysis and 3.21/2.24 g/g creatinine in the hybrid approach. However, the meta-regression showed that BMD and BMDL were significantly associated with the cut-off point, but BMD calculation method did not significantly affect the results. The urinary cadmium BMDL5 of β2-MG was 1.9 μg/g creatinine in the lowest cut-off point group.

Conclusion: The BMD was significantly associated with the cut-off point defining the abnormal level of renal dysfunction markers.

No MeSH data available.


Related in: MedlinePlus