Ludwig V. Lamberts

Co-exposure to lead increases the renal response to low levels of cadmium in metallurgy workers.

PURPOSE Research on the effect of co-exposure to Cd and Pb on the kidney is scarce. The objective of the present study was to assess the effect of co-exposure to these metals on biomarkers of early renal effect. METHODS Cd in blood (Cd-B), Cd in urine (Cd-U), Pb in blood (Pb-B) and urinary renal biomarkers, i.e., microalbumin (μ-Alb), beta-2-microglobulin (β₂-MG), retinol binding protein (RBP), N-acetyl-β-d-glucosaminidase (NAG), intestinal alkaline phosphatase (IAP) were measured in 122 metallurgic refinery workers examined in a cross-sectional survey. RESULTS AND CONCLUSIONS The median Cd-B, Cd-U, Pb-B were: 0.8 μg/l (IQR = 0.5, 1.2), 0.5 μg/g creatinine (IQR = 0.3, 0.8) and 158.5 μg/l (IQR = 111.0, 219.3), respectively. The impact of Cd-B on the urinary excretion of NAG and IAP was only evident among workers with Pb-B concentrations ≥ 75th percentile. The association between Cd-U and the renal markers NAG and RBP was also evidenced when Pb-B ≥ 75th percentile. No statistically significant interaction terms were observed for the associations between Cd-B or Cd-U and the other renal markers under study (i.e., μ-Alb and β2-MG). Our findings indicate that Pb increases the impact of Cd exposure on early renal biomarkers.

Selenium, Lead, and Cadmium Levels in Renal Failure Patients in China

Whole blood and serum samples of Chinese stable chronic renal failure (CRF) patients (n = 81), hemodialysis patients (n = 135), posttransplant patients (n = 60), and subjects with normal renal function (NRF; N = 42) were collected, as well as water and dialysate samples from five dialysis centers. The concentration of selenium (Se), lead (Pb), and cadmium (Cd) was measured by atomic absorption spectrometry. The mean serum Se levels in patients with different degrees of renal failure were significantly lower than those of subjects with NRF (p < 0.01). Pb levels were not increased in renal failure patients, while the Cd levels in patients with various degrees of renal failure were higher than in subjects with NRF (p < 0.05). After correcting the results of Pb and Cd for hematocrit (Hct) however, Pb levels of dialysis patients were also increased. In the dialysis population under study, blood Pb and Cd levels were closely related to the time on dialysis, while contamination of the final dialysate may also contribute to the increased blood Cd and to a less extent Pb levels. Correction for Hct may be recommended to accurately compare blood Pb and Cd levels in dialysis patients and CRF patients with varying degrees of anemia to those of subjects with NRF.

HPLC-AAS hybrid technique for studying the speciation of trace metals (Al, Fe, Si, Hg) in biological fluids: A review of applications, recent experiences and perspectives

A method developed using the combination of HPLC and AAS enabling both qualitative and quantitative study of the protein binding and speciation of trace metals in biological fluids at clinical relevant levels is reviewed. The whole system was made metal-free by using polymer-based columns, column holders and tubing and by the insertion of a silica-based scavenger column placed immediately before the injection valve to selectively retain any trace of aluminum and iron originating from buffer solutions and recipients. ETAAS instrumental conditions were carefully selected to eliminate interferences secondary to the salt gradient elution. Particular attention was paid to the choice of HPLC columns. Protein recoveries varied between 95 and 105% and trace metal recoveries were close to 100%. Intra-assay and inter-assay CVs of the HPLC/AAS hybrid technique were below 10%. Because of its high sensitivity, the method can be used at clinically relevant concentrations and was applied successfully to study (i) the interaction between iron and aluminum for binding to transferrin, (ii) the influence of citrate on the transferrin binding of aluminum, (iii) the speciation of silicon in the serum of dialysis patients and (iv) the toxicity of mercury compounds in cell cultures.

Aluminum an Uremic Toxin

Aluminum has historically been regarded as non essential, since up to now no physiological function could be ascribed to it. Environmental exposure to aluminum is virtually universal as aluminum constitutes a substantial part of the earth’s crust (8%) and is found in food, medicine and cosmetics. Besides this aluminum has a lot of industrial applications. Until recently, aluminum was generally considered to be a relatively nontoxic metal, which is reflected by the scarce and often wrong information presented in the literature dealing with the toxicology of trace elements. However, since it was found that aluminum is the causative factor in some dialysis-related diseases, the issue of the origin and physio-pathology of aluminum accumulation-toxicity in these patients has received the interest it deserves.

Aluminium accumulation/toxicity in dialysis patients: Monitoring, diagnosis and therapy∗

During the last ten years it has become evident that aluminium (Al) compounds are the causative factor of dialysis dementia and osteomalacia in patients with end‐stage renal failure (ESRF). Due to the availability of accurate analytical methods and the possibility for ultrastructural localization of Al in tissues, a substantial progress was made in the understanding and prevention of the Al‐related diseases. The use of desferrioxamine (DFO), a well known metal chelator has made an early diagnosis and effective therapy of Al‐overload possible. Furthermore, the application of appropriate systems for water treatment and the recognition of early risk factors such as diabetic nephropathy, chronic liver disease, parathyroidectomy and children with ESRF gave us the opportunity for secondary prevention. Notwithstanding this encouraging evolution, Al remains a problem in ESRF patients as long as aluminium hydroxide (Al(HO)3) is used as a phosphate binder. Therefore, regular monitoring of the serum Al levels is ess...

Plomo y nefropatía: Biomarcadores urinarios en la detección de daño renal precoz

The role of lead (Pb) as an environmental cause of nephropathy is difficult to ascertain due to the difficulty to determine clinically its exposure. Aim: To assess lead levels and renal function in a group of males working in mechanical workshops. Material and Methods: Blood and urine samples were obtained from 100 mechanical workshop workers aged 38 ± 16 years and 95 non-exposed office clerks aged 37 ± 17 years. Blood lead and creatinine levels were determined. In exposed workers, urinary excretion of intestinal alkaline phosphatases (IAP) and N-acetyl-glucosaminidase (NAG) were measured as early markers of renal failure. Results: Blood lead levels were 66.4 ± 43 and 33.6 ± 18 µg/L among mechanical workshop workers and non-exposed controls, respectively, p < 0.01. The figures for serum creatinine were 0.9 ± 0.1 and 0.9 ± 0.1 respectively, p = NS. Among exposed workers urinary excretion of IAP was 0.47 ± 0.6 U/L and of NAG, 0.92 ± 1.1 U/L. There was a positive correlation between blood lead levels and NAG excretion (r = 0.284) and IAP excretion (r = 0.346). Conclusions: Exposed workers had higher blood lead levels and there was a weak positive association between these levels and the urinary excretion of NAG and IAPUNLABELLED The role of lead (Pb) as an environmental cause of nephropathy is difficult to ascertain due to the difficulty to determine clinically its exposure. AIM To assess lead levels and renal function in a group of males working in mechanical workshops. MATERIAL AND METHODS Blood and urine samples were obtained from 100 mechanical workshop workers aged 38 ± 16 years and 95 non-exposed office clerks aged 37 ± 17 years. Blood lead and creatinine levels were determined. In exposed workers, urinary excretion of intestinal alkaline phosphatases (IAP) and N-acetyl-glucosaminidase (NAG) were measured as early markers of renal failure. RESULTS Blood lead levels were 66.4 ± 43 and 33.6 ± 18 µg/L among mechanical workshop workers and non-exposed controls, respectively, p < 0.01. The figures for serum creatinine were 0.9 ± 0.1 and 0.9 ± 0.1 respectively, p = NS. Among exposed workers urinary excretion of IAP was 0.47 ± 0.6 U/L and of NAG, 0.92 ± 1.1 U/L. There was a positive correlation between blood lead levels and NAG excretion (r = 0.284) and IAP excretion (r = 0.346). CONCLUSIONS Exposed workers had higher blood lead levels and there was a weak positive association between these levels and the urinary excretion of NAG and IAP.

119 Renal effects induced by occupational co-exposure to cadmium and lead in metallurgy workers

Objectives Research on the effect of co-exposure to Cd and Pb on the kidney is scarce. The objective of the present study was to assess the effect of co-exposure to these metals on early renal biomarkers. Methods Cd in blood (Cd-B), Cd in urine (Cd-U), Pb in blood (Pb-B) and urinary renal biomarkers i.e., microalbumin (µ-Alb), beta-2-microglobulin (β2-MG), retinol binding protein (RBP), N-acetyl-β-D-glucosaminidase (NAG), intestinal alkaline phosphatase (IAP) were measured in 122 metallurgic refinery workers examined in a cross-sectional survey. In order to explore the effect of Pb on the association between Cd and renal biomarkers (i.e., effect modification or interaction), we performed a multiple linear regression analysis (adjusting for age and pack-years of smoking) including an interaction term Pb x Cd. Results The median Cd-B, Cd-U, Pb-B were: 0.8 µg/l (IQR = 0.5, 1.2), 0.5 µg/g creatinine (IQR = 0.3, 0.8) and 158.5 µg/l (IQR = 111.0, 219.3), respectively. The statistically significant interaction term Pb-B x Cd-B indicates that the impact of Cd-B on the enzymes NAG and IAP was only evident among workers with Pb-B concentrations ≥ 75th percentile. The association between Cd-U and the renal markers NAG and RBP was also evidenced when Pb-B ≥ 75th percentile. No statistically significant interaction terms were observed for the associations between Cd-B or Cd-U and the other renal markers under study (i.e., µ-Alb and β2-MG). Conclusions Our findings indicate that Pb modifies (increases) the strength of the association between Cd and early renal biomarkers.