Detection of Cadmium and Lead in Kidney Stones. Associations with Patient Demographics, Stone Composition, and Smoking.

BACKGROUND: Kidney stones are a highly prevalent disease worldwide. Additionally, both environmental and occupational exposure to Pb and Cd continue to be prevalent globally and can result in renal toxicity. The objective of this study was to examine the potential presence of Pb and Cd in kidney stones, and to assess for correlation with demographic factors including smoking, gender, age, and kidney stone matrix composition. METHODS: Patient kidney stones (n = 96) were analyzed using Fourier transform infrared spectroscopy to identify the stone constituents. Cd and Pb concentrations (µg/g) were determined by inductively coupled plasma mass spectrometry. Cd and Pb concentrations were correlated using bivariable and multivariable statistical analysis with demographic factors (age, gender, smoking status), and kidney stone composition. RESULTS: Kidney stone Cd (median 0.092 µg/g, range 0.014 to 2.46) and Pb concentrations (median 0.95 µg/g, range 0.060 to 15.4) were moderately correlated (r = 0.56, P < 0.0001). Cd concentrations were positively associated with patient history of smoking, patient age, and calcium oxalate monohydrate levels while negatively associated with struvite and uric acid/uric acid dihydrate. Pb concentrations were positively associated with females and apatite levels while negatively associated with uric acid/uric acid dihydrate. After holding constant other stone type composition levels, smoking status, and age, both Pb and Cd were positively associated with apatite and negatively associated with uric acid/uric acid dihydrate, struvite, and calcium carbonate. CONCLUSIONS: Cd and Pb kidney stone concentrations are associated with specific kidney stone types. Cd and Pb kidney stone concentrations are both associated with smoking.

Isotopic composition of serum zinc and copper in healthy children and children with autism spectrum disorder in North America.

To better understand zinc and copper regulation and their involvement in various biochemical pathways as it relates to autism spectrum disorder (ASD), isotopic composition of serum zinc and copper were evaluated in both healthy children and children with ASD in North America. No significant difference in isotopic composition of serum zinc or copper with respect to healthy controls and ASD children were identified. However, the isotopic composition of serum copper in boys was found to be enriched in 65Cu in comparison to previously published healthy adult copper isotopic composition. Furthermore, in both boys and girls, the average isotopic composition of serum zinc is heavier than previously published healthy adult isotopic zinc composition. There was also a negative association between total zinc concentrations in serum and the zinc isotopic composition of serum in boys. Finally, children with heavier isotopic composition of copper also showed a high degree of variability in their zinc isotopic composition. While numerous studies have measured the isotopic composition of serum zinc and copper in adults, this is one of the first studies which measured the isotopic composition of serum copper and zinc in children, specifically those diagnosed with ASD. The results of this study showed that age and gender specific normal ranges of isotopic composition must be established to effectively use isotopic composition analysis in studying various diseases including ASD.

Establishment of a Labile Bound Copper Reference Interval in a Healthy Population via an Inductively Coupled Plasma Mass Spectrometry Dual Filtration-Based Assay.

CONTEXT.­: Clinical testing for Wilson disease (WD) is potentially challenging. Measuring the fraction of labile bound copper (LBC) to total copper may be a promising alternative diagnostic tool with better sensitivity and specificity than some current biomarker approaches. A dual filtration-based inductively coupled mass spectrometry (ICP-MS) assay to measure LBC in serum was developed. OBJECTIVE.­: To establish a reference interval for LBC and LBC to total copper (LBC fraction) in a healthy adult population, and to examine associations between total copper, LBC, and LBC fraction with age, sex, menopausal status, hormone replacement therapy, and supplement use. DESIGN.­: Serum samples were collected from healthy male (n = 110) and female (n = 104) patients between the ages of 19 and 80 years. Total copper and LBC were analyzed using ICP-MS. Results were used to calculate the LBC fraction. Reference intervals were calculated for the 2.5th and 97.5th percentiles for both LBC and LBC fraction. RESULTS.­: The reference intervals for LBC were determined to be 13 to 105 ng/mL and 12 to 107 ng/mL for female and male patients, respectively. The reference intervals for the LBC fraction were 1.0% to 8.1% and 1.2% to 10.5% for female and male patients, respectively. No significant associations were found regarding age, menopausal status, hormone replacement therapy, or vitamin and supplement use. CONCLUSIONS.­: Sex-specific reference intervals have now been established for LBC and LBC fraction. These data in conjunction with further testing of WD populations can be used to assess the sensitivity and specificity of LBC fraction in screening, monitoring, and diagnosis.

Assessment of gadolinium and iodine concentrations in kidney stones and correlation with contrast agent exposure, stone matrix composition, and patient demographic factors.

BACKGROUND: Gadolinium-based contrast agents (GBCAs) and Iodinated contrast media are widely utilized to increase medical imaging sensitivity. With predominant renal elimination, the potential for the incorporation of contrast agent derived gadolinium and iodine into kidney stones remains largely uncharacterized. The study objective was to measure gadolinium and iodine concentrations within kidney stones. Observed elemental concentrations were correlated with prior contrast agent administration, kidney stone composition, age, gender, and smoking status. METHODS: Kidney stones from 96 patients were analyzed by Fourier Transform Infrared Spectroscopy to determine stone composition. Residual kidney stone material was digested and analyzed by Inductively Coupled Plasma Mass Spectrometry to determine gadolinium and iodine concentrations. Univariable and multivariable lognormal linear regression were performed to study the relationship between kidney stone element concentrations and contrast agent administration, kidney stone composition, age, gender, and smoking status. RESULTS: Median iodine and gadolinium stone concentrations were 6.4 (range 0.6-3997) and 0.1 (range ≤0.013-113.5) µg/g respectively. Elevated gadolinium was strongly associated with GBCA history with a hazard rate of 2.20 (95 % CI 1.14-3.25 P < 0.001). Gadolinium was positively associated with smoking, as well as stones comprised of apatite and calcium oxalate. Iodine concentrations were negatively associated with uric acid stones. CONCLUSION: Gadolinium, but not iodine, concentrations in kidney stones was strongly correlated with contrast exposure history. Stone matrix composition and demographic factors, particularly smoking, can influence observed kidney stone elemental concentrations. Additional studies are needed to determine if exposure to gadolinium and iodine promote the formation of stone matrix and/or reflect exposure history.

Corrigendum: Evaluation of Zn, Cu, and Se Levels in the North American Autism Spectrum Disorder Population.

[This corrects the article DOI: 10.3389/fnmol.2021.665686.].

Evaluation of Zn, Cu, and Se Levels in the North American Autism Spectrum Disorder Population.

Metal ion dyshomeostasis and disparate levels of biometals like zinc (Zn), copper (Cu), and selenium (Se) have been implicated as a potential causative factor for Autism Spectrum Disorder (ASD). In this study, we have enrolled 129 children (aged 2-4 years) in North America, of which 64 children had a diagnosis of ASD and 65 were controls. Hair, nail, and blood samples were collected and quantitatively analyzed for Zn, Cu and Se using inductively coupled plasma mass spectrometry (ICP-MS). Of the analyzed biometals, serum Se (116.83 ± 14.84 mcg/mL) was found to be significantly lower in male ASD cases compared to male healthy controls (128.21 ± 9.11 mcg/mL; p < 0.005). A similar trend was found for nail Se levels in ASD (1.01 ± 0.15 mcg/mL) versus that of controls (1.11 ± 0.17 mcg/mL) with a p-value of 0.0132 using a stratified Wilcoxon rank sum testing. The level of Se in ASD cohort was co-analyzed for psychometric correlation and found a negative correlation between total ADOS score and serum Se levels. However, we did not observe any significant difference in Zn, Cu, and Zn/Cu ratio in ASD cases versus controls in this cohort of North American children. Further studies are recommended to better understand the biology of the relationship between Se and ASD status.

Discovery of an arsenic and mercury co-elevation in the Midwest United States using reference laboratory data.

This study aimed to determine if there is a co-elevation of human blood arsenic and mercury levels in the Midwestern population of the United States (U.S.) and to determine any geographical patterns and variation of arsenic and mercury that may exist in Michigan. 58,800 blood specimens along with associated demographic/geographic data from the contiguous United States were reviewed. Univariate and multivariable logistic regression were used to analyze demographic/geographic variables associated with elevated arsenic concentrations. Furthermore, blood data from patients in Michigan were aggregated to the ZIP code tabulation area (ZCTA) in order to assess geographic variation using spatial regression models. SaTScan software was also used to analyze potential clustering of arsenic and mercury across Michigan ZCTAs. Within the contiguous United States, elevated mercury blood concentrations, older age, female sex, and coastal status were all associated with elevated arsenic blood concentrations (elevated mercury odds ratio (OR) 3.18 (3.04-3.33); female sex OR 1.06 (1.02-1.11); +10 yr age OR 1.12 (1.11-1.14); coastal state OR 1.33 (1.27-1.40). Within the state of Michigan, as with the continuous U.S., elevated mercury blood concentrations and older age were associated with elevated arsenic blood concentrations (elevated mercury OR 2.75 (2.38-3.18); female sex OR 1.06 (0.95-1.19); +10 yr age OR 1.10 (1.06-1.13). Using spatial regression, it was determined that within Michigan, economic inequality (measured via the Gini coefficient) was also associated with elevated concentrations of mercury in the blood. Clinical reference laboratory data, in conjunction with spatial analysis methods, may enhance our understanding of how elemental exposure affects human health and should be considered for studying how environmental contaminants, socioeconomics and geography affect the health of populations.

Establishing human heart chromium, cobalt and vanadium concentrations by inductively coupled plasma mass spectrometry.

OBJECTIVE: Chromium, cobalt, and vanadium are used in metallic joint prosthesis. Case studies have associated elevated heart tissue cobalt concentrations with myocardial injury. To document the long term heart metal ion concentrations, a validated inductively coupled plasma mass spectroscopy (ICP-MS) method was needed. METHOD: The method utilized a closed-vessel microwave digestion system to digest the samples. An ICP-MS method utilizing Universal Cell Technology was used to determine our target analyte concentrations. Accuracy was verified using reference materials. Precision, sensitivity, recovery and linearity studies were performed. This method was used to establish a reference range for a non-implant containing cohort of 80 autopsy human heart tissues RESULTS: This method demonstrated an analytic measurement range of 0.5-100ng/mL for each element. Accuracy was within ±10% of target value for each element. Within-run precision for each element was below 20% CV. The chromium, vanadium and cobalt concentrations (mean±SD) were 0.1523±0.2157µg/g, 0.0094±0.0211µg/g and 0.1039±0.1305µg/g respectively in 80 non-implant containing human heart tissue samples. CONCLUSIONS: This method provides acceptable recovery of the chromium, cobalt and vanadium in heart tissue; allowing assessment of the effects of metallic joint prosthesis on myocardial health.

Myocardial Cobalt Levels Are Elevated in the Setting of Total Hip Arthroplasty.

BACKGROUND: Arthroplasty implants commonly contain elemental metal that may undergo wear-related release. Recently, cases of hip implant-associated myocardial injury have been reported. However, we are not aware of any previous study that has systematically measured myocardial metal levels or examined the relationship with total hip arthroplasty (THA). METHODS: Archives of our institution were queried for autopsies of individuals who had undergone THA between 1990 and 2013. Myocardial tissue samples were analyzed for cobalt (Co) and chromium (Cr) levels with inductively coupled plasma mass spectroscopy. Seventy-five Co/Cr-on-polyethylene THA cases were included (mean age at time of death = 77.4 years; 49% women) as were 73 non-arthroplasty controls matched for age, sex, and history of hypertension and diabetes mellitus. RESULTS: Significantly higher median myocardial concentrations of Co were observed in individuals with THA compared with controls (0.12 versus 0.06 µg/g, p < 0.0001). The median Co concentration was 69% higher in patients who had undergone THA revision (0.169 µg/g) than in those who underwent primary THA (0.100 µg/g; p = 0.004). In general, higher Co levels were observed in those with multiple replaced joints, although this finding only trended toward significance. Cardiomegaly, interstitial fibrosis, and decreased ejection fraction were observed more frequently in the postmortem samples of patients with implants than in those of controls (p = 0.0002, 0.044, and 0.0039, respectively). CONCLUSIONS: We believe this to be the first study to quantify metal levels in cardiac tissue in patients with and without joint replacement. The elevated Co levels, in concert with cardiomegaly and increased interstitial fibrosis found during autopsy, in the arthroplasty cohort are novel, important findings. Although Co levels were significantly elevated above those in controls, the majority were below those seen in clinical case reports of death from Co cardiotoxicity associated with metal-on-metal prostheses. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.