Evaluation of harmful drinking among professional drivers by direct ethanol biomarkers and its relation with psychological distress.

OBJECTIVE: This study aimed to evaluate the alcohol consumption among professional truck and bus drivers using direct ethanol biomarkers, and to explore its relationship with anxiety, depression, and stress. METHODS: The assessment of potential harmful drinking was conducted through the measurement of direct biomarkers: phosphatidylethanol (PEth), ethyl glucuronide (EtG), and ethyl sulfate (EtS), using dried blood spots (DBS). Additionally, self-reported data from the Alcohol Use Disorders Identification Test (AUDIT-C) were used. Emotional states, including depression, anxiety, and stress, were evaluated using the Depression, Anxiety, and Stress Scale (DASS-21). RESULTS: A total of 97 drivers participated in the study, with the majority being male (96%) and identified as truck drivers (75.3%). Among them, 43.3% reported working more than 10 h daily. The majority of volunteers exhibited normal levels of stress (81.4%), anxiety (83%), and depression (86.6%). According to the AUDIT-C assessment, 30.9% were categorized as having a moderate risk, while 11.3% were deemed to be at high risk for harmful alcohol consumption behavior. Ethyl glucuronide (EtG) and ethyl sulfate (EtS) levels, indicating recent ethanol consumption, were detected in 14.4% of the drivers. In contrast, the long half-life metabolite PEth (16:0-18:1) was present in 88.7% of the volunteers. A moderate correlation (rs = 0.45, p < .01) was observed between PEth levels and AUDIT-C scores. The Receiver Operating Characteristic (ROC) curve, utilizing a PEth threshold of ≥ 59.0 ng ml-1, displayed 78% sensitivity and 73% specificity in effectively distinguishing high risk for alcohol intake. Notably, no significant associations were found between alcohol consumption and levels of stress, depression, and anxiety. CONCLUSIONS: The study findings indicate a noteworthy proportion of drivers engaging in regular alcohol consumption alongside a demanding workload. Notably, PEth measurements highlighted an underreporting within the AUDIT-C self-reports. These results lend robust support for the utilization of biomarkers in assessing alcohol consumption patterns among drivers.

Can curcumin supplementation reduce plasma levels of gut-derived uremic toxins in hemodialysis patients? A pilot randomized, double-blind, controlled study.

BACKGROUND: Gut dysbiosis is common in patients with chronic kidney disease (CKD) and is closely related to inflammatory processes. Some nutritional strategies, such as bioactive compounds present in curcumin, have been proposed as an option to modulate the gut microbiota and decrease the production of uremic toxins such as indoxyl sulfate (IS), p-cresyl sulfate (pCS) and indole-3 acetic acid (IAA). OBJECTIVE: To evaluate the effects of curcumin supplementation on uremic toxins plasma levels produced by gut microbiota in patients with CKD on hemodialysis (HD). METHODS: Randomized, double-blind trial in 28 patients [53.6 ± 13.4 years, fourteen men, BMI 26.7 ± 3.7 kg/m2, dialysis vintage 37.5 (12-193) months]. Fourteen patients were randomly allocated to the curcumin group and received 100 mL of orange juice with 12 g carrot and 2.5 g of turmeric and 14 patients to the control group who received the same juice but without turmeric three times per week after HD sessions for three months. IS, pCS, IAA plasma levels were measured by reverse-phase high-performance liquid chromatography RESULTS: After three months of supplementation, the curcumin group showed a significant decrease in pCS plasma levels [from 32.4 (22.1-45.9) to 25.2 (17.9-37.9) mg/L, p = 0.009], which did not occur in the control group. No statistical difference was observed in IS and IAA levels in both groups. CONCLUSION: The oral supplementation of curcumin for three months seems to reduce p-CS plasma levels in HD patients, suggesting a gut microbiota modulation.

Bowel Habits and the Association With Uremic Toxins in Non-Dialysis-Dependent Chronic Kidney Disease Patients.

OBJECTIVE: The aim of this study is to evaluate the association between bowel habits and microbial-derived uremic toxins p-cresyl sulfate (PCS) and indoxyl sulfate (IS) in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). DESIGN AND METHODS: This is a cross-sectional analysis including 43 nondiabetic NDD-CKD patients (58% men; 59.0 ± 13.5 years; estimated glomerular filtration rate, 21.3 ± 7.9 mL/min/1.73 m2). Bowel habit was assessed by the Bristol Stool Scale (BSS <3, characterized by hard consistency of stools and/or low frequency of evacuation and BSS ≥3, representing a more regular bowel habit) and by the Rome III criteria. PCS and IS (serum, free and total; urinary, total) were determined by high-performance liquid chromatography. Dietary intake was assessed by the 3-day food records. RESULTS: The frequency of constipation assessed by BSS and Rome III criteria was 33% (n = 14/43) and 35% (n = 15/43), respectively. The BSS <3 exhibited higher PCS, independent of renal function and dietary protein-fiber ratio (ß [95% confidence interval {CI}]: serum, total PCS = 1.54 [1.06-2.23], P = .02; serum free PCS = 1.40 [1.00-1.97], P = .05; urinary PCS = 1.78 [1.10-2.90], P < .02). According to the Rome III criteria, a tendency for a higher serum total PCS (ß [95% CI]: 1.39 [0.95-2.03 µmol/L], P = .09) and a significantly higher urinary PCS (ß [95% CI]: 1.80 [1.11-2.94 µmol/24 h], P = .02) was found in constipated participants. No effect of a compromised bowel habit (Rome III criteria or BSS) was found on IS. CONCLUSION: Constipation may lead to production of PCS in nondiabetic NDD-CKD patients.

The specific impact of uremic toxins upon cognitive domains: a review / O impacto específico de toxinas urêmicas em domínios cognitivos: uma revisão

ABSTRACT One of the mechanisms proposed for chronic kidney disease (CKD)-related cognitive impairment is the accumulation of uremic toxins due to the deterioration of the renal clearance function. Cognition can be categorized into five major domains according to its information processing functions: memory, attention, language, visual-spatial, and executive. We performed a review using the terms 'uric acid', 'indoxyl sulfate', 'p-cresyl sulfate', 'homocysteine', 'interleukins' and 'parathyroid hormone'. These are the compounds that were found to be strongly associated with cognitive impairment in CKD in the literature. The 26 selected articles point towards an association between higher levels of uric acid, homocysteine, and interleukin 6 with lower cognitive performance in executive, attentional, and memory domains. We also reviewed the hemodialysis effects on cognition. Hemodialysis seems to contribute to an amelioration of CKD-related encephalopathic dysfunction, although this improvement occurs more in some cognitive domains than in others.

RESUMO Um dos mecanismos propostos para explicar o comprometimento cognitivo relacionado à doença renal crônica (DRC) é o acúmulo de toxinas urêmicas devido à deterioração da função de depuração renal. A cognição pode ser categorizada em cinco domínios principais de acordo com suas funções de processamento de informações: memória, atenção, linguagem, visual-espacial e executiva. Realizamos uma revisão usando os termos "ácido úrico", "indoxil sulfato", "p-cresil sulfato", "homocisteína", "interleucinas" e "paratormônio". Estes são os compostos que se mostraram fortemente associados ao comprometimento cognitivo na DRC na literatura. Os 26 artigos selecionados apontam para uma associação entre níveis mais elevados de ácido úrico, homocisteína e interleucina-6 com menor desempenho cognitivo nos domínios executivo, atenção e de memória. Também revisamos os efeitos da hemodiálise na cognição. A hemodiálise parece contribuir para uma melhoria da disfunção encefalopática relacionada à DRC, embora essa melhora ocorra mais em alguns domínios cognitivos do que em outros.

Removal of Protein-Bound Uremic Toxins during Hemodialysis Using a Binding Competitor.

BACKGROUND AND OBJECTIVES: Current hemodialysis techniques fail to efficiently remove the protein-bound uremic toxins p-cresyl sulfate and indoxyl sulfate due to their high degree of albumin binding. Ibuprofen, which shares the same primary albumin binding site with p-cresyl sulfate and indoxyl sulfate, can be infused during hemodialysis to displace these toxins, thereby augmenting their removal. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We infused 800 mg ibuprofen into the arterial bloodline between minutes 21 and 40 of a conventional 4-hour high-flux hemodialysis treatment. We measured arterial, venous, and dialysate outlet concentrations of indoxyl sulfate, p-cresyl sulfate, tryptophan, ibuprofen, urea, and creatinine before, during, and after the ibuprofen infusion. We report clearances of p-cresyl sulfate and indoxyl sulfate before and during ibuprofen infusion and dialysate concentrations of protein-bound uremic toxins normalized to each patient's average preinfusion concentrations. RESULTS: We studied 18 patients on maintenance hemodialysis: age 36±11 years old, ten women, and mean vintage of 37±37 months. Compared with during the preinfusion period, the median (interquartile range) clearances of indoxyl sulfate and p-cresyl sulfate increased during ibuprofen infusion from 6.0 (6.5) to 20.2 (27.1) ml/min and from 4.4 (6.7) to 14.9 (27.1) ml/min (each P<0.001), respectively. Relative median (interquartile range) protein-bound uremic toxin dialysate outlet levels increased from preinfusion 1.0 (reference) to 2.4 (1.2) for indoxyl sulfate and to 2.4 (1.0) for p-cresyl sulfate (each P<0.001). Although median serum post- and predialyzer levels in the preinfusion period were similar, infusion led to a marked drop in serum postdialyzer levels for both indoxyl sulfate and p-cresyl sulfate (-1.0 and -0.3 mg/dl, respectively; each P<0.001). The removal of the nonprotein-bound solutes creatinine and urea was not increased by the ibuprofen infusion. CONCLUSIONS: Infusion of ibuprofen into the arterial bloodline during hemodialysis significantly increases the dialytic removal of indoxyl sulfate and p-cresyl sulfate and thereby, leads to greater reduction in their serum levels.

The specific impact of uremic toxins upon cognitive domains: a review.

One of the mechanisms proposed for chronic kidney disease (CKD)-related cognitive impairment is the accumulation of uremic toxins due to the deterioration of the renal clearance function. Cognition can be categorized into five major domains according to its information processing functions: memory, attention, language, visual-spatial, and executive. We performed a review using the terms 'uric acid', 'indoxyl sulfate', 'p-cresyl sulfate', 'homocysteine', 'interleukins' and 'parathyroid hormone'. These are the compounds that were found to be strongly associated with cognitive impairment in CKD in the literature. The 26 selected articles point towards an association between higher levels of uric acid, homocysteine, and interleukin 6 with lower cognitive performance in executive, attentional, and memory domains. We also reviewed the hemodialysis effects on cognition. Hemodialysis seems to contribute to an amelioration of CKD-related encephalopathic dysfunction, although this improvement occurs more in some cognitive domains than in others.

The Impact of Uremic Toxicity Induced Inflammatory Response on the Cardiovascular Burden in Chronic Kidney Disease.

Uremic toxin (UT) retention in chronic kidney disease (CKD) affects biological systems. We aimed to identify the associations between UT, inflammatory biomarkers and biomarkers of the uremic cardiovascular response (BUCVR) and their impact on cardiovascular status as well as their roles as predictors of outcome in CKD patients. CKD patients stages 3, 4 and 5 (n = 67) were recruited and UT (indoxyl sulfate/IS, p-cresil sulfate/pCS and indole-3-acetic acid/IAA); inflammatory biomarkers [Interleukin-6 (IL-6), high sensitivity C reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1), soluble vascular adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble Fas (sFas)] and BUCVRs [soluble CD36 (sCD36), soluble receptor for advanced glycation end products (sRAGE), fractalkine] was measured. Patients were followed for 5.2 years and all causes of death was used as the primary outcome. Artery segments collected at the moment of transplantation were used for the immunohistochemistry analysis in a separate cohort. Estimated glomerular filtration rate (eGFR), circulating UT, plasma biomarkers of systemic and vascular inflammation and BUCVR were strongly interrelated. Patients with plaque presented higher signs of UT-induced inflammation and arteries from CKD patients presented higher fractalkine receptor (CX3CR1) tissue expression. Circulating IS (p = 0.03), pCS (p = 0.007), IL-6 (p = 0.026), sFas (p = 0.001), sCD36 (p = 0.01) and fractalkine (p = 0.02) were independent predictors of total mortality risk in CKD patients. Our results reinforce the important role of uremic toxicity in the pathogenesis of cardiovascular disease (CVD) in CKD patients through an inflammatory pathway.