Low-Fiber Intake Is Associated With High Production of Intraperitoneal Inflammation Biomarkers.

OBJECTIVE: Fiber intake influences disturbances in the gastrointestinal tract and is associated with systemic inflammation in the general population. Systemic and intraperitoneal inflammation play an important role in defining outcomes in peritoneal dialysis (PD), but the relationship between dietary fiber intake and inflammatory biomarkers has not yet been reported in the population on PD. The objective of the present study is to analyze whether or not fiber intake in patients on PD is associated with serum and intraperitoneal levels of inflammatory biomarkers. DESIGN AND METHODS: Adult and clinically stable PD patients were included in this observational and cross-sectional study. Fiber intake was assessed by means of a dietary survey and calculated using the DietPro program 5.6i. The population was divided into two groups according to the median fiber intake. We investigated interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, monocyte chemoattractant protein-1 (MCP-1), B-cell-activating factor, and plasminogen-activator inhibitor-1 in both serum and peritoneal fluid. The latter was determined after a dwell time of 4 hours. RESULTS: Fifty-two patients (42% men; aged 53 ± 14 years, 36% diabetics) were evaluated. Low intake of dietary fiber was found in 90% of patients, with a median of 12.2 g per day (3.4-33.3). The group with the highest fiber intake presented lower intraperitoneal levels of IL-6, IL-8, and MCP-1. In contrast, only MCP-1 was lower in the serum of those who consumed more fiber. All the associations remained significant after adjustment for confounders with plasminogen-activator inhibitor-1 included. CONCLUSIONS: Patients on PD frequently present inadequate dietary fiber intake, which appears to have an association with the inflammatory response, particularly in the intraperitoneal component. Further prospective studies, evaluating whether or not a dietetic intervention with a focus on fiber intake affects these biomarkers and clinical outcomes, are essential to determine causality and clinical relevance.

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.

Evaluation of Salt Intake, Urinary Sodium Excretion and Their Relationship to Overhydration in Chronic Kidney Disease Patients.

The purpose of this study was to estimate sodium intake in a group of patients with chronic kidney disease (CKD) and to correlate the results with the urinary excretion values of sodium and signs of fluid overload. We included patients with CKD in different stages. Urinary sodium was measured in 24 h urine samples. Body composition monitor (BCM) was used to estimate the hydration status. Sixty patients (38 ± 15 ml/min of GFR) presented 4.14 ± 1.71 g/24 h of urinary sodium excretion. Overhydration was detected in 50% of the patients by the BCM. There was a positive correlation between the measured sodium excretion values and BCM, ICW, ECW and TBW. In conclusion, markers of overhydration evaluated by BCM were positively correlated with urinary sodium excretion.

Association between biomarkers of carbonyl stress with increased systemic inflammatory response in different stages of chronic kidney disease and after renal transplantation.

BACKGROUND: Chronic kidney disease (CKD) is characterized by progressive kidney dysfunction accompanied by accumulation of uremic toxins and a potential disequilibrium between the redox status and the generation of prooxidants, resulting in oxidative stress and chronic inflammation which is associated with complications (particularly cardiovascular disease) in this population. We aimed to analyze the concentration of total plasma thiols (indicator of antioxidant capacity) and the protein carbonyl content (a marker of carbonyl stress) in relation to kidney function and inflammation in a group of patients with CKD. PATIENTS AND METHODS: A group of 68 patients with CKD (stages 2-5; mean age 57 ± 12 years, 46% male, 34% diabetics) and another group of 21 patients who underwent living donor kidney transplantation (mean age 36 ± 17 years, 50% male, 10% diabetics, and 9 ± 2 months after renal transplantation) were included in the study. Total plasma thiol and protein carbonyl levels were determined by the DTNB and DNPH methods, respectively, and were adjusted to the plasma albumin concentrations. Plasma levels of fibrinogen and C-reactive protein (CRP) were measured by routine methods and used as markers of inflammation. RESULTS: Mean glomerular filtration rate (GFR) was 48 ml/min, and there was a positive correlation between GFR and thiol (r = 0.25, p < 0.05) and a negative correlation between GFR and carbonyl (r = -0.26, p < 0.05), fibrinogen (r = -0.45, p < 0.0001) and CRP (r = -0.14, p = ns). Carbonyl strongly correlated with CRP (0.49, p < 0.0001) and fibrinogen (0.30, p < 0.01). There was a significant reduction in plasma carbonyl after renal transplantation (1.4 ± 0.4 nmol/mg albumin), compared with the levels before the procedure (2.0 ± 1.4 nmol/mg albumin, p < 0.05), which parallels an improvement in thiol levels (15 ± 4 vs. 21 ± 5 nmol/mg albumin, p < 0.001). In addition, there was a significant correlation between CRP and carbonyl after the transplantation (r = 0.65; p < 0.005). CONCLUSION: We observed that patients with CKD present an altered redox status and increased signs of carbonyl stress and inflammatory activity as kidney function deteriorates, which was partially but significantly improved after renal transplantation. These findings indicate the importance of renal function in the complications of CKD related to oxidative stress and inflammation.

Effect of vitamin C, deferoxamine, quercetin and rutin against tert-butyl hydroperoxide oxidative damage in human erythrocytes.

The mature human erythrocyte, when submitted to oxidative stress, can demonstrate depletion of reduced glutathione, oxidation of the hemoglobin molecule and aggregation of complexes of iron close to the membrane. These can produce abnormalities in the erythrocyte membrane and hemolysis. The aim of this work was to study the antioxidative action of vitamin C (vit. C), deferroxamine (DFO) and the flavonoids quercetin and rutin in normal human erythrocytes, submitted to in vitro oxidative stress induced by tert-butylhydroperoxide ((t)BHP). Venous blood was collected in citrate-phosphate-dextrose (CPD) solution, as anticoagulant, from healthy adult individuals after informed consent. The erythrocytes were resuspended in PBS to obtain 35% globular volume, and then submitted to the oxidative action of (t)BHP for up to 30 min, with or without previous incubation for 60 min with vit. C, DFO, quercetin and rutin. Decrease in the GSH concentration, G6-PD and GR activities, and increase in the methemoglobin and Heinz bodies (HB) formation, occurred with the increase in (t)BHP concentration. (t)BHP did not effect on the membrane proteins detected by SDS-PAGE. Quercetin, partially prevented the GSH decrease and the formation of HB, but did not prevent MetHb formation from oxidative damage by (t)BHP. Rutin, after (t)BHP induction, prevented the GSH decrease and the formation of HB. Vit. C, had no influence on the depletion of GSH, inhibited partially the metHb formation, and it protected GR, but not G6-PD from oxidative damage by (t)BHP. DFO partially inhibited the metHb formation and GSH decrease, but it did not protect GR and G6-PD from oxidative damage by (t)BHP. The results obtained suggest that vit. C, DFO and the flavonoids quercetin and rutin contribute to the decrease in the oxidative stress caused by (t)BHP.

Effect of vitamins C and E on oxidative processes in human erythrocytes.

The oxidative action of 1 mmol l(-1) phenylhydrazine hydrochloride (PH) was studied on human erythrocytes treated with the antioxidants vitamin C (vit. C) and vitamin E (vit. E). The erythrocytes were resuspended in PBS to obtain 35% cell packed volume, and then submitted to the oxidative action of PH for 20 min, with or without previous incubation for 60 min with vit. C or vit. E. Heinz bodies and methemoglobin formation by PH were inhibited in the presence of vit. C. At the concentration of 90 mmol l(-1), vit. C, not only seemed to lose its antioxidant effect, but it also promoted an increase in methemoglobin formation. Vit. C (0.5-80 mmol l(-1)) did not protect against GSH depletion by PH. Vit. C alone produced insignificant hemolysis, but, in the presence of PH, the hemolysis indices were more accentuated. Heinz body formation by PH was inhibited in the presence of vit. E. Formation of methemoglobin induced by PH was decreased by vit. E (0.1-2 mmol l(-1)), although vit. E (3-80 mmol l(-1)) did not lower the concentration of methemoglobin and did not lead to the recovery of the GSH depleted by PH. The results obtained suggest that vit. C and vit. E contribute to the decrease in oxidative stress caused by PH.

Meio CE e glutaraldeído na preservaçäo de plaquetas para o controle de qualidade em hematimetria / CE medium and gluutaraldehyde in platelets preservation for control quality in hematology

Controles comerciais para todas as medidas hematológicas só se tornaram disponíveis no início da década de 60, sendo que ainda há falta de padronizaçäo apropriada para diversas medidas envolvendo componentes celulares. As amostras comerciais de células consistem de células de sangue humano ou de outros animais, alteradas para retardar a deterioraçäo. De um modo geral, os fabricantes utilizam para essas células os termos: fixadas, tamponadas, estabilizadas ou preservadas, para indicar o seu processo de preparo, sem contudo descrevê-lo. Em trabalhos anteriores, desenvolveu-se amostras adequadas ao controle de qualidade em hematimetria, estáveis para os valores do eritrograma durante 100 dias, pela preservaçäo de eritrócitos em meio CE, composto por glicose, NaCl, citrato de sódio, fosfato monohidrógeno de sódio, KCl, EDTANa2, albumina bovina, clormicetina, neomicina e cortisona e pela fixaçäo parcial com glutaraldeído [ Leonart, Rev. Bras. Anál. Clín. 21: 111, 1989 ]. O uso de soluçöes aditivas para o armazenamento de concentrados de plaquetas tem aumentado durante os últimos anos e se tornado frequente na prática clínica. Em testes preliminares, realizados com o meio CE para a preservaçäo de plaquetas humanas, observamos estabilidade para a sua contagem durante até 35 dias [ Emendörfer et al, Rev. Bras. Anál. Clín. 31:18, 1999]. A partir de 20 amostras de sangue venoso em EDTAK2 e da obtençäo do plasma rico em plaquetas, testou-se a fixaçäo parcial em glutaraldeído, com posterior ressuspensäo das plaquetas em meio CE, obtendo-se valores estáveis para contagem em Coulter Counster T890 durante até 50 dias. Foram estudadas modificaçöes na composiçäo do meio CE nas concentraçöes de 1 a 6 g/gL de albumina bovina, obtendo-se maior estabilidade para as amostras de plaquetas preservadoras na concentraçäo de 6 g/dL, como empregada no meio CE original. No entanto, em amostras fixadas com glutaraldeído näo se observou diferenças na contagem das plaquetas durante 50 dias, independentemente da concentraçäo de albumina bovina. Os resultados obtidos sugerem que a fixaçäo parcial com glutaraldeído pode ser adequada para a estabilizaçäo de plaquetas em amostras de controle de qualidade.