Association between Enzyme-Linked Immunosorbent Assay-Measured Kidney Injury Markers and Urinary Cadmium Levels in Chronic Kidney Disease

Cadmium exposure is associated with chronic kidney disease (CKD), but the optimal biomarker for early cadmium-associated nephrotoxicity in low-level exposure has not yet been established. We conducted a cross-sectional investigation involving 167 CKD patients stratified according to tertiles of urinary cadmium levels (UCd), in which enzyme-linked immunosorbent assay (ELISA)-measured novel renal biomarkers were utilized to assess the extent of renal injury associated with cadmium burden. In the analyses, urinary kidney injury molecule-1 (KIM-1) levels and age were the independent factors positively correlated with UCd after adjusting for covariates in non-dialysis-dependent CKD patients (high vs. low UCd, odds ratio (95% confidence interval), 1.0016 (1.0001–1.0032), p = 0.043, and 1.0534 (1.0091–1.0997), p = 0.018). Other conventional and novel renal biomarkers, such as serum creatinine, estimated glomerular filtration rate, CKD staging, urinary protein/creatinine ratio, urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), and urinary epidermal growth factor (EGF) were not independently correlated with UCd in the analyses. In conclusion, our study found that the ELISA-measured urinary KIM-1 level could serve as an early renal injury marker in low-level cadmium exposure for non-dialysis-dependent CKD patients. In addition, age was an independent factor positively associated with UCd in this population.

Association Between Cadmium Exposure and Liver Function in Adults in the United States: A Cross-sectional Study

Objectives: Cadmium is widely used, leading to extensive environmental and occupational exposure. Unlike other organs, for which the harmful and carcinogenic effects of cadmium have been established, the hepatotoxicity of cadmium remains unclear. Some studies detected correlations between cadmium exposure and hepatotoxicity, but others concluded that they were not associated. Thus, we investigated the relationship between cadmium and liver damage in the general population.Methods: In total, 11 838 adult participants from National Health and Nutrition Examination Survey 1999-2015 were included. Urinary cadmium levels and the following liver function parameters were measured: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), total bilirubin (TB), and alkaline phosphatase (ALP). Linear and logistic regression analyses were performed to assess the associations between urinary cadmium concentrations and each liver function parameter after adjusting for age, sex, race/ethnicity, annual family income, smoking status, alcohol consumption status, physical activity, and body mass index.Results: The covariate-adjusted results of the linear regression analyses showed significant positive relationships between log-transformed urinary cadmium levels and each log-transformed liver function parameter, where beta±standard error of ALT, AST, GGT, TB, and ALP were 0.049±0.008 (p<0.001), 0.030±0.006 (p<0.001), 0.093±0.011 (p<0.001), 0.034±0.009 (p<0.001), and 0.040±0.005 (p<0.001), respectively. Logistic regression also revealed statistically significant results. The odds ratios (95% confidence intervals) of elevated ALT, AST, GGT, TB, and ALP per unit increase in log-transformed urinary cadmium concentration were 1.360 (1.210 to 1.528), 1.307 (1.149 to 1.486), 1.520 (1.357 to 1.704), 1.201 (1.003 to 1.438), and 1.568 (1.277 to 1.926), respectively.Conclusions: Chronic exposure to cadmium showed positive associations with liver damage.

Prevalence of abnormal urinary cadmium and risk of albuminuria as a primary bioindicator for kidney problems among a healthy population

Background The prevalence of chronic kidney disease is increasing globally, ranking 27th as the cause of death in the 1990s, rising to 18th in 2010 and 10th in 2019. Non-communicable diseases such as diabetes and hypertension have been identified as the common contributing factors, while there is also evidence linking environmental pollutants, especially cadmium, to kidney disease. This study aimed at investigating the level of urinary cadmium and its relationship to albuminuria as an early indicator of kidney problems in the Kepong community. Methods Respondents were surveyed as part of several health-related programs organized by the Kepong District Health Office involving local communities in and around the district from April 2019 to December 2019. Urinalysis of two urine samples was carried out using a Mission reagent strip and an Inductively Coupled Plasma Mass Spectrometry (ICP-MS) test to detect the presence and level of urinary cadmium. Results A total of 240 respondents were enrolled from April 2019 to December 2019. Urinalysis of two urine samples was carried out using a Mission reagent strip and an Inductively Coupled Plasma Mass Spectrometry (ICP-MS) test to detect the level of urinary cadmium. The respondents’ average age was 41-year-old (±13.23). Among them, 49.6% were male, 85.0% Malay, 5.8% Chinese and 8.3% Indian. 55.0% had background of tertiary, 39.6% secondary and 5.4% primary level of education. 52.1% were categorized in B40, 34.6% in M40 and 13.3% in T20 based on monthly household income category. 26.7% were hypertensive, 6.7% diabetic, 4.2% had dyslipidemia, 51.7% had urinary cadmium above the alert level, and 27.1% had albuminuria. Discussion Risk factors for albuminuria that have been identified are age with adjusted odds ratio (AOR) 3.53 (1.41–8.83; p < 0.05), highest educational level with AOR 2.18 (1.14–4.17; p < 0.05), diabetes with AOR 3.36 (1.07–10.52; p < 0.05), and urinary cadmium with AOR 4.72 (2.33–9.59; p < 0.001), with future screening programs placing greater attention to those at risk and further research is required to determine the cause of exposure to cadmium.

Bone morphogenetic protein 4 as a biomarker for cadmium-associated bone damage

Background Cadmium is a well-characterized bone toxic agent and can induce bone damage via inhibiting osteogenic differentiation. However, only a few studies have addressed the mechanism on cadmium-associated bone damage and none of them has used a panel of sensitive and specific biomarkers for the detection of cadmium-associated bone damage. BMP/SAMD signaling pathway can mediate osteogenic differentiation, but the association between cadmium and BMP/SAMD signaling pathway is yet to be illuminated. Methods We treated human bone marrow mesenchymal stem cells (BMSCs) with CdCl2 in vitro to to detect the expression of BMPs and SAMDs. And we also enrolled 67 cases of bone damage and 67 cases without bone damage. Urinary cadmium concentration and the concentrations of BMP-2 and BMP-4 of subjects were detected. Mediation analyses was used to estimate the influence of urinary cadmium and BMP-4 on bone damage, adjusting for a set of confounders. Results Cd exposure significantly promoted adipogenic differentiation of hBMSCs, and inhibited its' osteogenic differentiation by inhibiting the expression of BMP-2/4, SAMD4, and p-SAMD1/5/9 complex. BMP-4 mediated 22.92% (95%CI 6.37, 46.00) of the total association between cadmium and the risk of osteoporosis. Conclusions We found BMP-4 can be a diagnostic biomarker and therapeutic target of cadmium-associated bone damage.

The Relationship between the Urinary Cadmium Concentration and Cause-Specific Mortality in Subjects without Severe Renal Damage: A 35-Year Follow-Up Study in a Cadmium-Polluted Area of Japan

We evaluated the association between urinary cadmium concentration (uCd, μg/g Cr) and risk of cause-specific mortality according to urinary β2-microglobulin (MG) concentration. Participants were 1383 male and 1700 female inhabitants of the Cd-polluted Kakehashi River basin. The uCd and β2-MG were evaluated in a survey in 1981–1982, where those participants were followed-up over 35 years later. Among the participants with a urinary β2-MG < 1000, the hazard ratios (HRs) (95% confidence interval) for mortality were significantly higher in those with a uCd of ≥ 10.0 compared with < 5.0 for cardiovascular disease [HR 1.92 (1.08–3.40) for men, 1.71 (1.07–2.71) for women], pneumonia or influenza [2.10 (1.10–4.00) for men, 2.22 (1.17–4.19) for women], and digestive diseases [for men; 3.81 (1.49–9.74)]. The uCd was significantly associated with mortality from heart failure in women and digestive diseases in men, after adjustment for other causes of death using the Fine and Gray competing risk regression model. For participants with a urinary β2-MG of ≥ 1000, no significant association was observed between uCd and any major cause of death. In the absence of kidney damage, Cd may increase the risk of death from cardiovascular disease, pneumonia, and digestive diseases.