Search

Background: The relationship between selenium and renal function has always attracted widespread attention. Increased selenium level has been found to cause impaired renal function in our previous study, but the mechanism is not clear. In this study, we evaluate the potential mediating effects of plasma proteome in the association of selenium level and renal function to understand the mechanisms of selenium's effect on renal function., Methods: Utilizing two-sample two-step mediating mendelian randomization (MR) methodology to investigate the genetically causal relationship between selenium level and renal function as well as the role of the plasma proteome in mediating them. Additionally, the mediating proteins were enriched and analyzed through bioinformatics to understand the potential mechanisms of selenium effects on renal function., Results: In the MR analysis, an increase in selenium level was found to decrease estimated glomerular filtration rate (eGFR). Specifically, for each standard deviation (SD) increase in selenium levels, eGFR levels are reduced by 0.003 SD [Beta (95% CI): -0.003 (-0.004 ~ -0.001), P=0.001, with no observed heterogeneity and pleiotropy]. Through mediation analysis, 35 proteins have been determined mediating the genetically causal effects of selenium on the levels of eGFR, including Fibroblast growth factor receptor 4 (FGFR4), Fibulin-1, Cilia- and flagella-associated protein 45, Mothers against decapentaplegic homolog 2 (SMAD2), and E3 ubiquitin-protein ligase ZNRF3, and the mediation effect rates of these proteins ranged from 1.59% to 23.70%. In the enrichment analysis, 13 signal transduction pathways, including FGFR4 mutant receptor activation and Defective SLC5A5 causing thyroid dyshormonogenesis 1, were involved in the effect of selenium on eGFR levels., Conclusion: Our finding has revealed the underlying mechanism by which increased selenium level lead to deterioration of renal function, effectively guiding the prevention of chronic kidney disease and paving the way for future studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fu, Qian, Yuan, Su, Ma, Li and Xu.)

In solid-organ transplantation, microRNAs (miRNAs) have emerged as key players in the regulation of allograft cells function in response to injury. To gain insight into the role of miRNAs in antibody-mediated rejection, a rejection phenotype histologically defined by microvascular inflammation, kidney allograft biopsies were subjected to miRNA but also messenger RNA (mRNA) profiling. Using a unique multistep selection process specific to the BIOMARGIN study (discovery cohort, N=86; selection cohort, N=99; validation cohort, N=298), six differentially expressed miRNAs were consistently identified: miR-139-5p (down) and miR-142-3p/150-5p/155-5p/222-3p/223-3p (up). Their expression level gradually correlated with microvascular inflammation intensity. The cell specificity of miRNAs target genes was investigated by integrating their in vivo mRNA targets with single-cell RNA sequencing from an independent allograft biopsy cohort. Endothelial-derived miR-139-5p expression correlated negatively with MHC-related genes expression. Conversely, epithelial-derived miR-222-3p overexpression was strongly associated with degraded renal electrolyte homeostasis and repressed immune-related pathways. In immune cells, miR-150-5p regulated NF-κB activation in T lymphocytes whereas miR-155-5p regulated mRNA splicing in antigen-presenting cells. Altogether, integrated omics enabled us to unravel new pathways involved in microvascular inflammation and suggests that metabolism modifications in tubular epithelial cells occur as a consequence of antibody-mediated rejection, beyond the nearby endothelial compartment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tinel, Lamarthée, Callemeyn, Van Loon, Sauvaget, Morin, Aouni, Rabant, Gwinner, Marquet, Naesens and Anglicheau.)

Genes underneath signals from genome-wide association studies (GWAS) for kidney function are promising targets for functional studies, but prioritizing variants and genes is challenging. By GWAS meta-analysis for creatinine-based estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease Genetics Consortium and UK Biobank (n = 1,201,909), we expand the number of eGFRcrea loci (424 loci, 201 novel; 9.8% eGFRcrea variance explained by 634 independent signal variants). Our increased sample size in fine-mapping (n = 1,004,040, European) more than doubles the number of signals with resolved fine-mapping (99% credible sets down to 1 variant for 44 signals, ≤5 variants for 138 signals). Cystatin-based eGFR and/or blood urea nitrogen association support 348 loci (n = 460,826 and 852,678, respectively). Our customizable tool for Gene PrioritiSation reveals 23 compelling genes including mechanistic insights and enables navigation through genes and variants likely relevant for kidney function in human to help select targets for experimental follow-up., (© 2021. The Author(s).)

Background: Viral mediated gene therapy has progressed after overcoming early failures, and gene therapy has now been approved for several conditions in Europe and the USA. Glycogen storage disease (GSD) type Ia, caused by a deficiency of glucose-6-phosphatase-α, has been viewed as an outstanding candidate for gene therapy. This follow-up report describes the long-term outcome for the naturally occurring GSD-Ia dogs treated with rAAV-GPE-hG6PC-mediated gene therapy., Methods: A total of seven dogs were treated with rAAV-GPE-hG6PC-mediated gene therapy. The first four dogs were treated at birth, and three dogs were treated between 2 and 6 months of age to assess the efficacy and safety in animals with mature livers. Blood and urine samples, radiographic studies, histological evaluation, and biodistribution were assessed., Results: Gene therapy improved survival in the GSD-Ia dogs. With treatment, the biochemical studies normalized for the duration of the study (up to 7 years). None of the rAAV-GPE-hG6PC-treated dogs had focal hepatic lesions or renal abnormalities. Dogs treated at birth required a second dose of rAAV after 2-4 months; gene therapy after hepatic maturation resulted in improved efficacy after a single dose., Conclusion: rAAV-GPE-hG6PC treatment in GSD-Ia dogs was found to be safe and efficacious. GSD-Ia is an attractive target for human gene therapy since it is a monogenic disorder with limited tissue involvement. Blood glucose and lactate monitoring can be used to assess effectiveness and as a biomarker of success. GSD-Ia can also serve as a model for other hepatic monogenic disorders.

Background: Kidney transplantation using grafts with multiple vessels (GMVs) is technically demanding and may be associated with increased risk of complications or suboptimal graft function. To date, no studies have reported on robot-assisted kidney transplantation (RAKT) using GMVs., Objective: To report our experience with RAKT using GMVs from living donors, focusing on technical feasibility and early postoperative outcomes., Design, Setting, and Participants: We reviewed the multi-institutional, prospectively collected European Association of Urology (EAU) Robotic Urology Section (ERUS)-RAKT database to select consecutive patients undergoing RAKT from living donors using GMVs between July 2015 and January 2018. Patients undergoing RAKT using grafts with single vessels (GSVs) served as controls. In case of GMVs, ex vivo vascular reconstruction techniques were performed during bench surgery according to the case-specific anatomy., Intervention: RAKT with regional hypothermia., Outcome Measurements and Statistical Analysis: Intraoperative outcomes and early (30 d) postoperative complications and functional results were the main study endpoints. Multivariable logistic regression analysis evaluated potential predictors of suboptimal renal function at 1 mo., Results and Limitations: Overall, 148 RAKTs were performed during the study period. Of these, 21/148 (14.2%) used GMVs; in all cases, single arterial and venous anastomoses could be performed after vascular reconstruction. Median anastomoses and rewarming times did not differ significantly between the GMV and GSV groups. Total and cold ischemia times were significantly higher in the GMV cohort (112 vs 88min, p=0.004 and 50 vs 34min, p=0.003, respectively). Overall complication rate and early functional outcomes were similar among the two groups. No major intra- or postoperative complications were recorded in the GMV cohort. At multivariable analysis, use of GMVs was not significantly associated with suboptimal renal function at 1 mo. Small sample size and short follow-up represent the main study limitations., Conclusions: RAKT using GMVs from living donors is technically feasible and achieved favorable perioperative and short-term functional outcomes. Larger studies with longer follow-up are needed to confirm our findings., Patient Summary: In this study, we evaluated for the first time in literature the results of RAKT from living donors using kidneys with multiple arteries and veins. We found that, in experienced centers, RAKT using kidneys with multiple vessels is feasible and achieves optimal results in terms of postoperative kidney function with a low number of postoperative complications., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Data on long-term toxicity of antiretroviral therapy (ART) in HIV-infected children are sparse. PENPACT-1 was an open-label trial in which HIV-infected children were assigned randomly to receive protease inhibitor (PI)- or nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based ART., Methods: We examined changes in clinical, immunologic, and inflammatory markers from baseline to year 4 in the subset of children in the PENPACT-1 study who experienced viral suppression between week 24 and year 4 of ART. Liver enzyme, creatinine, and cholesterol levels and hematologic parameters were assessed during the trial. Cystatin C, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), d-dimer, and soluble CD14 (sCD14) were assayed from cryopreserved specimens., Results: Ninety-nine children (52 on PI-based and 47 on NNRTI-based ART) met inclusion criteria. The median age at initiation of ART was 6.5 years (interquartile range [IQR], 3.7-13.4 years), and 22% were aged <3 years at ART initiation; 56% of the PI-treated children received lopinavir/ritonavir, and 70% of NNRTI-treated children received efavirenz initially. We found no evidence of significant clinical toxicity in either group; growth, liver, kidney, and hematologic parameters either remained unchanged or improved between baseline and year 4. Total cholesterol levels increased modestly, but no difference between the groups was found. IL-6 and hs-CRP levels decreased more after 4 years in the NNRTI-based ART group. The median change in IL-6 level was -0.35 pg/ml in the PI-based ART group and -1.0 in the NNRTI-based ART group (P = .05), and the median change in hs-CRP level was 0.25 µg/ml in the PI-based ART group and -0.95 µg/ml in the NNRTI-based ART group (P = .005)., Conclusion: These results support the safety of prolonged ART use in HIV-infected children and suggest that suppressive NNRTI-based regimens can be associated with lower levels of systemic inflammation., (© The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Congenital abnormalities of the kidney and urinary tract (CAKUT) account for approximately half of children with chronic kidney disease and they are the most frequent cause of end-stage renal disease in children in the US. However, its genetic etiology remains mostly elusive. VACTERL association is a rare disorder that involves congenital abnormalities in multiple organs including the kidney and urinary tract in up to 60% of the cases. By homozygosity mapping and whole-exome resequencing combined with high-throughput mutation analysis by array-based multiplex PCR and next-generation sequencing, we identified recessive mutations in the gene TNF receptor-associated protein 1 (TRAP1) in two families with isolated CAKUT and three families with VACTERL association. TRAP1 is a heat-shock protein 90-related mitochondrial chaperone possibly involved in antiapoptotic and endoplasmic reticulum stress signaling. Trap1 is expressed in renal epithelia of developing mouse kidney E13.5 and in the kidney of adult rats, most prominently in proximal tubules and in thick medullary ascending limbs of Henle's loop. Thus, we identified mutations in TRAP1 as highly likely causing CAKUT or VACTERL association with CAKUT.

Objectives: Renal impairment (RI) is a predictor of poor outcomes in patients with cardiovascular disease, but its influence in the setting of percutaneous coronary intervention and zotarolimus-eluting stent (ZES) implantation has not been described. This study evaluated the impact of RI on clinical outcomes in patients participating in the E-Five Registry., Background: E-Five was a prospective, multicenter, global registry of 8,314 patients; 2,116 patients were followed to 2 years., Methods: Patients (excluding those who had undergone renal transplantation) were grouped according to renal function (normal function/mild RI, serum creatinine <110 μmol/L; moderate RI, 110-200 μmol/L; severe RI, >200 μmol/L) and their outcomes evaluated retrospectively. Major adverse cardiac events (MACE; i.e., death, myocardial infarction, emergency cardiac bypass surgery, or target lesion revascularization) and stent thrombosis events at 1 and 2 years were compared between groups., Results: The 1-year MACE rate in patients with mild RI was 6.8%, compared with 8.9 and 18.1% in patients with moderate and severe RI (P = 0.002 across groups). At 2 years, death occurred in 16% of those with severe RI, compared with 2.0 and 4.7% in those with mild and moderate RI (P = 0.002). There was no significant difference in the rates of target lesion revascularization or target vessel failure., Conclusions: Greater severity of RI at intervention is associated with greater mortality and MACE but unchanged revascularization rates after ZES implantation., (Copyright © 2012 Wiley Periodicals, Inc.)

The zoonotic potential of paramyxoviruses is particularly demonstrated by their broad host range like the highly pathogenic Hendra and Nipah viruses originating from bats. But while so far all bat-borne paramyxoviruses have been identified in fruit bats across Africa, Australia, South America, and Asia, we describe the detection and characterization of the first paramyxoviruses in free-ranging European bats. Moreover, we examined the possible impact of paramyxovirus infection on individual animals by comparing histo-pathological findings and virological results. Organs from deceased insectivorous bats of various species were sampled in Germany and tested for paramyxovirus RNA in parallel to a histo-pathological examination. Nucleic acids of three novel paramyxoviruses were detected, two viruses in phylogenetic relationship to the recently proposed genus Jeilongvirus and one closely related to the genus Rubulavirus. Two infected animals revealed subclinical pathological changes within their kidneys, suggestive of a similar pathogenesis as the one described in fruit bats experimentally infected with Hendra virus.Our findings indicate the presence of bat-born paramyxoviruses in geographic areas free of fruit bat species and therefore emphasize a possible virus-host co-evolution in European bats. Since these novel viruses are related to the very distinct genera Rubulavirus and Jeilongvirus, a similarly broad genetic diversity among paramyxoviruses in other Microchiroptera compared to Megachiroptera can be assumed. Given that the infected bats were either found in close proximity to heavily populated human habitation or areas of intensive agricultural use, a potential risk of the emergence of zoonotic paramyxoviruses in Europe needs to be considered.

Variants in the gene encoding the γ-subunit of the epithelial sodium channel (SCNN1G) are associated with both Mendelian and quantitative effects on blood pressure. Here, in 4 cohorts of 1611 white European families composed of a total of 8199 individuals, we undertook staged testing of candidate single-nucleotide polymorphisms for SCNN1G (supplemented with imputation based on data from the 1000 Genomes Project) followed by a meta-analysis in all of the families of the strongest candidate. We also examined relationships between the genotypes and relevant intermediate renal phenotypes, as well as expression of SCNN1G in human kidneys. We found that an intronic single-nucleotide polymorphism of SCNN1G (rs13331086) was significantly associated with age-, sex-, and body mass index-adjusted blood pressure in each of the 4 populations (P<0.05). In an inverse variance-weighted meta-analysis of this single-nucleotide polymorphism in all 4 of the populations, each additional minor allele copy was associated with a 1-mm Hg increase in systolic blood pressure and 0.52-mm Hg increase in diastolic blood pressure (SE=0.33, P=0.002 for systolic blood pressure; SE=0.21, P=0.011 for diastolic blood pressure). The same allele was also associated with higher 12-hour overnight urinary potassium excretion (P=0.04), consistent with increased epithelial sodium channel activity. Renal samples from hypertensive subjects showed a nonsignificant (P=0.07) 1.7-fold higher expression of SCNN1G compared with normotensive controls. These data provide genetic and phenotypic evidence in support of a role for a common genetic variant of SCNN1G in blood pressure determination.

High-dose (75 mg/m2) cisplatin is baseline chemotherapy in lung cancer. To prevent nephrotoxicity, patients generally receive saline infusion on the day of chemotherapy prior to and following cisplatin (total of 3.5-4.0 liters during 3-4 hours). Despite these measures nephrotoxicity has remained frequent, especially among patients also suffering from cardiovascular disease or diabetes mellitus. Since 2005 several international recommendations have been formed about prevention of cisplatin nephrotoxicity. According to these recommendations: 1) renal function should not be evaluated by serum creatinine concentration; 2) evaluation of renal function should be based on calculated creatinine clearance (e.g. by the Cockcroft-Gault equation); 3) patients to be treated by high-dose cisplatin should be euvolemic and should have saline diuresis (urine NaCl concentration ~1%) of at least 100 ml/hour prior to, during and several days following the administration of cisplatin. Keeping these recommendations ensures prolonged cisplatin treatability of lung cancer patients. Moreover, decreased renal function will not limit the full dose administration of several other cytotoxic agents. Losonczy G, Máthé C, Müller V, Szondy K, Moldvay J. Incidence, risk factors and prevention of cisplatin-induced nephrotoxicity in patients with lung cancer.

Background: Blocking the tubuloglomerular feedback mechanism with adenosine A1 receptor antagonists seems to improve diuresis and sodium excretion without compromising the glomerular filtration rate in patients with heart failure. However, the direct cardiac effects of this compound class have not been investigated to date., Methods and Results: In total, 111 patients (109 men and 2 women) received a 1-hour infusion of 5, 10, and 15 mg SLV320, an adenosine A1 receptor antagonist, placebo, or 40 mg furosemide. Mean age was 57.9 years, mean ejection fraction was 28.1%, 82 patients were of New York Heart Association class II, and 29 patients were of New York Heart Association class III. Hemodynamic parameters (heart rate, blood pressure, pulmonary capillary wedge pressure, mean pulmonary arterial pressure, systemic vascular resistance, right atrial pressure, and cardiac output) were determined. Kidney function was assessed by cystatin C measurements and by analysis of urine output and urine electrolytes. In addition, pharmacokinetics of SLV320 and ex vivo inhibition of adenosine A1 receptor activity were performed. SLV320 was well tolerated, and no serious adverse events were observed. Heart rate, blood pressure, pulmonary capillary wedge pressure, mean pulmonary arterial pressure, right atrial pressure, and cardiac output were not altered by any dose of SLV320. Pulmonary capillary wedge pressure was significantly (P=0.04) decreased by furosemide (-6.2+/-5.9 mm Hg). Systemic vascular resistance was significantly (P=0.04) increased in the furosemide group (+166.70+/-261.87 dynes . s(-1) . cm(-5)), whereas all SLV320 groups showed no significant alterations of systemic vascular resistance. Changes from baseline cystatin C plasma concentrations decreased after 10 mg SLV320 (-0.093+/-0.137 mg/L, P=0.046), whereas furosemide resulted in a significant (P=0.03) increase of cystatin C (+0.052+/-0.065 mg/L) versus baseline. All values represent mean changes+/-SD from baseline at 3 hours postdosing: SLV320 (10 and 15 mg) increased significantly sodium excretion and diuresis compared with placebo during the 0- to 6-hour collection period postdosing., Conclusions: SLV320 infusion shows no immediate effects on cardiac hemodynamics. SLV320 might improve glomerular filtration rate while simultaneously promoting natriuresis and diuresis. Clinical Trial Registration- clinicaltrials.gov Indentifier: NCT00160134.

(1) Dental amalgam is one of the main sources of exposure to mercury in industrialised countries; (2) At high doses, mercury is both neurotoxic and nephrotoxic. A suspected link exists between chronic exposure to low doses of mercury derived from dental amalgam and renal, neurodegenerative or neurobehavioural disorders, but it has not been established; (3) Some individual cases are troubling, but epidemiological studies show no major effects in the general population. Various hypotheses have been proposed to explain why some people may be more sensitive than others to the effects of low-dose mercury; (4) More and more countries, especially Sweden, recommend that the use of amalgam should be restricted, particularly in pregnant women and children; (5) As part of a global strategy to eliminate mercury, the European Parliament has asked the Commission to draft legislation limiting the use of mercury in dental amalgam; (6) Evaluation of the risk-benefit balances of alternatives to dental amalgam does not provide sufficient data on which to base an informed choice between available options.

Despite the recent discovery of significant genetic structuring in a large number of marine organisms, the evolutionary significance of these often minute genetic differences are still poorly understood. To elucidate the adaptive relevance of low genetic differentiation among marine fish populations, we studied expression differences of osmoregulatory and stress genes in genetically weakly differentiated populations of the European flounder (Platichthys flesus), distributed across a natural salinity gradient. Flounders were maintained in a long-term reciprocal transplantation experiment mimicking natural salinities in the North Sea and the Baltic Sea. Applying real-time quantitative PCR and microarray analysis we studied expression of four candidate genes (hsp70, angiotensinogen, Na/K-ATPase-alpha and 5-aminolevulinic acid synthase (ALAS)) in gill, kidney and liver tissues. Genes involved in osmoregulative processes (Na/K-ATPases-alpha and angiotensinogen) showed highly plastic but similar expression in the two populations dependent on environmental salinity. However, we observed a unique sixfold up-regulation of hsp70 in kidney tissue of flounder from the North Sea following long-term acclimation to Baltic salinities. Similarly, significant differences between North Sea and Baltic flounders in expression of ALAS in response to different salinities were found in gill and liver tissue. These findings strongly suggest that gene expression in flounders is shaped by adaptation to local environmental conditions. This identification of adaptive differences in high gene flow marine organisms adds a new dimension to our current understanding of evolutionary processes in the sea and is of paramount importance for identification, protection and sustainable management of marine biodiversity.

Selected trace elements (Cd, Cu, Hg, Se, Zn) were measured in the kidneys and the liver of 104 harbour porpoises (Phocoena phocoena) stranded along the coasts of France, Galicia (Spain), Ireland, Scotland (UK), and the Netherlands. Generally, relatively low concentrations of toxic elements were encountered in the tissues of European porpoises, except for two individuals, which displayed high hepatic Hg concentrations. Also, elevated Cd levels obtained in Scottish porpoises could be related to their feeding preferences and this result suggests an increase of the proportion of cephalopods in their diet with latitude. Moreover, significant geographical differences were seen in hepatic Zn concentrations; the elevated Zn concentrations displayed by porpoises from the Netherlands may relate their poor health status. Variation in metal concentrations within porpoises from the North Sea is likely to reflect a long-term segregation between animals from northern (Scotland) and southern areas (the Netherlands), making trace elements powerful ecological tracers.

Background: Information about residual renal function (RRF) and outcomes associated with practices of diuretic use in patients with end-stage renal disease is not available worldwide., Methods: Diuretic use was investigated in 16,420 hemodialysis patients from the Dialysis Outcomes and Practice Patterns Study, a prospective observational study of hemodialysis patients selected from nationally representative facilities on 3 continents. Logistic regressions were used to investigate associations between diuretic use and patient characteristics. Outcomes of interdialytic weight gain, increased serum potassium and phosphorus levels, and odds of retaining RRF after 1 year were investigated. Cox regression was used to analyze the association between mortality and diuretic use., Results: Facility diuretic use varied substantially from 0% to 83.9% of patients. Diuretic use decreased sharply after the start of dialysis therapy. Loop diuretic use ranged from 9.2% in the United States to 21.3% in Europe, whereas use within 90 days of starting dialysis therapy ranged from 25.0% in the United States to 47.6% in Japan. Diuretic use was associated with lower interdialytic weight gain and lower odds of hyperkalemia (potassium > 6.0 mmol/L). Patients with RRF on diuretic therapy had almost twice the odds of retaining RRF after 1 year in the study versus patients not on diuretic therapy. Patients administered diuretics had a 7% lower all-cause mortality risk (P = 0.12) and 14% lower cardiac-specific mortality risk (P = 0.03) versus patients not administered diuretics., Conclusion: Variation exists in facility practices of diuretic use. In patients with RRF, there may be benefit associated with continuing diuretic use rather than automatically discontinuing diuretic therapy at dialysis initiation.

Cd, Cu and Zn were analysed in the organs and tissues of the three scallop species from the Bay of Biscay, the variegated Chlamys varia L., the queen scallop Aequipecten opercularis L. and the common scallop Pecten maximus L. for interspecific comparisons. In P. maximus the greatest concentrations of Cd and Cu were found in the digestive gland, whereas the two other species showed similar levels of Cd between digestive gland and kidneys and higher renal Cu concentrations. However, the digestive gland of all Pectinidae species contained from 75% to 93% and 52% to 74% of the total body burdens of Cd and Cu, respectively. Whatever the species, kidneys displayed the highest Zn concentrations, which therefore contained from 53% to 97% of the total body burden of this metal. Also using reported results, ratios between the concentrations in the digestive gland and that in the kidneys discriminated two groups of Pectinidae: (1) the Pecten group (P. maximus, P. jacobeus and Adamussium colbecki) with a Cd ratio > or = 4, a Cu ratio > or = 1 and a Zn ratio > 20x10(-3); (2) the Chlamys group with a Cd ratio < or = 1, a Cu ratio < or = 1 and a Zn ratio < or = 6x10(-3). However, no differences in the detoxification processes in the digestive gland were found between groups in this study. 72-80% of the total Cd was found to be soluble, probably bound to metalloproteins such as metallothioneins, while Cu and Zn were mainly found associated to the insoluble fraction of the digestive gland cells whatever the species. Queen scallops from the Faroe Islands were also considered to examine variations of the metal concentrations due to the geographical origin. In this northern area, queen scallops displayed Cd concentrations 2, 4 and 6 times higher in kidneys, muscle and digestive gland, respectively, compared to those from the Bay of Biscay. Consequently, the Cd concentrations in the whole soft parts of the queen scallops were more than 6 times higher in the Faroe Islands than in the Bay of Biscay. In contrast to Cd, both Cu and Zn concentrations in the whole soft parts were 2 times lower in the Faroe Islands, suggesting lower bioavailability of these essential elements.