Environment-Wide Association Study of CKD

Lee, Jeonghwan; Oh, Sohee; Kang, Habyeong; Kim, Sunmi; Lee, Gowoon; Li, Lilin; Kim, Clara Tammy; An, Jung Nam; Oh, Yun Kyu; Lim, Chun Soo; Kim, Yon Su; Choi, Kyungho; Lee, Jung Pyo

doi:10.2215/cjn.06780619

Cited by 46 publications

(26 citation statements)

References 61 publications

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“…Environmental exposures are estimated to account for 70–90% of the risk of acquiring chronic ailments such as diabetes type 2, CKD and cancer [ 271 , 272 ]. The kidney is particularly at risk of injury from long-term use of therapeutic drugs and chronic exposure to environmental toxicants, especially when they are present in the diet [ 273 , 274 , 275 ].…”

Section: Environmental Exposure To CD and Pb Toxic Kidney Burdenmentioning

confidence: 99%

“…CKD afflicts 8% to 16% of the world population. Diabetes and hypertension are the most common risk factors universally, while obesity is an additional risk factor, especially in industrialized countries [ 272 , 273 , 274 , 275 , 276 , 277 , 278 , 279 ]. CKD is a cause of morbidity and mortality as it is an important predictor of end-stage kidney disease (ESKD), stroke and cardiovascular disease (CVD) [ 280 , 281 , 282 , 283 , 284 , 285 ].…”

Section: Environmental Exposure To CD and Pb Toxic Kidney Burdenmentioning

confidence: 99%

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Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

Satarug

Gobé

Vesey

et al. 2020

Toxics

128

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The present review aims to provide an update on health risks associated with the low-to-moderate levels of environmental cadmium (Cd) and lead (Pb) to which most populations are exposed. Epidemiological studies examining the adverse effects of coexposure to Cd and Pb have shown that Pb may enhance the nephrotoxicity of Cd and vice versa. Herein, the existing tolerable intake levels of Cd and Pb are discussed together with the conventional urinary Cd threshold limit of 5.24 μg/g creatinine. Dietary sources of Cd and Pb and the intake levels reported for average consumers in the U.S., Spain, Korea, Germany and China are summarized. The utility of urine, whole blood, plasma/serum, and erythrocytes to quantify exposure levels of Cd and Pb are discussed. Epidemiological studies that linked one of these measurements to risks of chronic kidney disease (CKD) and mortality from common ailments are reviewed. A Cd intake level of 23.2 μg/day, which is less than half the safe intake stated by the guidelines, may increase the risk of CKD by 73%, and urinary Cd levels one-tenth of the threshold limit, defined by excessive ß2-microglobulin excretion, were associated with increased risk of CKD, mortality from heart disease, cancer of any site and Alzheimer’s disease. These findings indicate that the current tolerable intake of Cd and the conventional urinary Cd threshold limit do not provide adequate health protection. Any excessive Cd excretion is probably indicative of tubular injury. In light of the evolving realization of the interaction between Cd and Pb, actions to minimize environmental exposure to these toxic metals are imperative.

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Section: Environmental Exposure To CD and Pb Toxic Kidney Burdenmentioning

confidence: 99%

Section: Environmental Exposure To CD and Pb Toxic Kidney Burdenmentioning

confidence: 99%

Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

Satarug

Gobé

Vesey

et al. 2020

Toxics

128

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“…In particular, early-life exposure to common nephrotoxic Children 2021, 8, 673 2 of 14 elements, such as arsenic (As), cadmium (Cd), and lead (Pb), may disrupt nephrogenesis and primary renal developmental processes that are vital for nutrientwaste homeostasis [3]. As, Cd, and Pb are established nephrotoxicants, pervasive in the environment [4][5][6], with substantial evidence of glomerular or tubular toxicity [7][8][9] as well as nephrotoxic effects in children [10][11][12][13][14][15][16]. However, their joint impact on renal development as a mixture is less well known.…”

Section: Introductionmentioning

confidence: 99%

“…Because early-life exposure to nephrotoxicants may lead to kidney function decline, examining exposure to multiple toxicants individually and as a mixture is increasingly important in the context of real-life exposures. For example, blood Pb and Cd exposure have been individually associated with a reduced estimated glomerular filtration rate (eGFR) and co-exposure to both toxicants increases CKD risk [6,18]. Pb and Cd have also been shown to act non-additively, resulting in worse kidney function decline in adults [6,[19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Nephrotoxic Metal Mixtures and Preadolescent Kidney Function

et al. 2021

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Exposure to metals including lead (Pb), cadmium (Cd), and arsenic (As), may impair kidney function as individual toxicants or in mixtures. However, no single medium is ideal to study multiple metals simultaneously. We hypothesized that multi-media biomarkers (MMBs), integrated indices combining information across biomarkers, are informative of adverse kidney function. Levels of Pb, Cd, and As were quantified in blood and urine in 4–6-year-old Mexican children (n = 300) in the PROGRESS longitudinal cohort study. We estimated the mixture effects of these metals, using weighted quantile sum regression (WQS) applied to urine biomarkers (Umix), blood biomarkers (Bmix), and MMBs, on the cystatin C-based estimated glomerular filtration rate (eGFR) and serum cystatin C assessed at 8–10 years of age, adjusted for covariates. Quartile increases in Umix and the MMB mixture were associated with 2.5% (95%CI: 0.1, 5.0) and 3.0% (95%CI: 0.2, 5.7) increased eGFR and −2.6% (95% CI: −5.1%, −0.1%) and −3.3% (95% CI: −6.5%, −0.1%) decreased cystatin C, respectively. Weights indicate that the strongest contributors to the associations with eGFR and serum cystatin C were Cd and Pb, respectively. MMBs detected mixture effects distinct from associations with individual metals or media-type, highlighting the benefits of incorporating information from multiple exposure media in mixtures analyses.

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“…There is evidence to suggest that Cd exposure plays a role in the development of chronic kidney disease (CKD) and that Cd can be nephrotoxic at environmental levels [ 5 , 7 ]. A recent exposure-wide association study of over 250 chemicals found that Cd was associated with CKD [ 8 ]. Therefore, identifying preventable risk factors, including environmental exposures in childhood, could contribute to our knowledgebase of early-life intervenable factors for decreasing the incidence of CKD [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Early-Life Dietary Cadmium Exposure and Kidney Function in 9-Year-Old Children from the PROGRESS Cohort

Rodríguez-López

Tamayo‐Ortiz

Ariza

et al. 2020

Toxics

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Cadmium (Cd) is a toxic metal associated with adverse health effects, including kidney injury or disease. The aims of this study were to estimate dietary Cd exposure during childhood, and to evaluate the association of early-life dietary Cd with biomarkers of glomerular kidney function in 9-year-old Mexican children. Our study included 601 children from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort with up to five follow-up food frequency questionnaires from 1 to 9 years of age; and 480 children with measures of serum creatinine, cystatin C, and blood nitrogen urea (BUN), as well as 9-year-old estimated glomerular filtration rate. Dietary Cd was estimated through food composition tables. Multiple linear regression models were used to analyze the association between 1 and 9 years, cumulative dietary Cd, and each kidney parameter. Dietary Cd exposure increased with age and exceeded the tolerable weekly intake (TWI = 2.5 µg/kg body weight) by 16–64% at all ages. Early-life dietary Cd exposure was above the TWI and we observed inverse associations between dietary Cd exposure and kidney function parameters. Additional studies are needed to assess kidney function trajectories through adolescence. Identifying preventable risk factors including environmental exposures in early life can contribute to decreasing the incidence of adult kidney disease.

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Environment-Wide Association Study of CKD

Cited by 46 publications

References 61 publications

Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

Nephrotoxic Metal Mixtures and Preadolescent Kidney Function

Early-Life Dietary Cadmium Exposure and Kidney Function in 9-Year-Old Children from the PROGRESS Cohort

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