The effects of medium cut-off and high-flux membranes on activated clotting time of patients on hemodialysis.

Introduction: The interaction between blood and dialysis membrane increases the risk of clot formation. Membrane properties can interfere with coagulation activation during dialysis. Heparin is usually used to ensure anticoagulation, which can be monitored by the Activated Clotting Time (ACT) test. The purpose of this study was to compare the ACT of patients with chronic kidney disease (CKD) undergoing hemodialysis with high-flux (HF) and medium cut-off (MCO) membranes. Methods: This is a prospective, randomized, crossover study in which 32 CKD patients were dialyzed for 12 weeks with each membrane. Blood clotting measured by ACT was evaluated at the beginning, 2nd, and 4th hour of the dialysis session. Throughout the study, there were no changes in the dose or administration method of heparin. Results: Patients mainly were middle-aged, non-black males on hemodialysis for eight years. Before randomization, ACT values were 132 ± 56, 195 ± 60, and 128 ± 32 seconds at pre-heparinization, 2nd and 4th hour, respectively. After 12 weeks, ACT values in HF and MCO groups were 129 ± 17, 205 ± 65 and 139 ± 38 seconds, and 143 ± 54, 219 ± 68 and 142 ± 45 seconds, respectively. An ANOVA model adjusted and unadjusted for repeated measures showed a significant time but no treatment or interaction effects. In an additional paired-sample analysis, no difference between ACT values of HF and MCO Groups was observed. Discussion and Conclusion: There was no difference regarding the ACT test during dialysis therapy using HF or MCO membranes. This data suggests that no adjustment in the dose or administration method of heparin is necessary with the use of MCO dialysis membranes.

Chronic kidney disease induces inflammation by increasing Toll-like receptor-4, cytokine and cathelicidin expression in neutrophils and monocytes.

TLR expression in neutrophils and monocytes is associated with increased cytokine synthesis, resulting in increased inflammation. However, the inflammatory pathway related to TLR and cathelicidin expression in these cells from CKD patients is unclear. To evaluate TLR4, cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 expression in neutrophils and monocytes from HD and CKD patients. Blood samples were drawn from 47 CKD and 43 HD patients and 71 age and gender-matched healthy volunteers (CONT). TLR4 was analyzed using flow cytometry. Cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 were analyzed via ELISA.TLR4 expression in neutrophils was higher in HD patients than in stage 3 and 4 CKD patients. In these cells, we observed a positive correlation between TLR4 and cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 levels. In monocytes, TLR4 expression was significantly higher in CKD 3 and 4 groups than in the control and HD groups and positively and negatively correlated with IL-6 and MCP-1 and cathelicidin, respectively. TNF-α, IL-6 and MCP-1 serum levels were higher in HD and CKD patients than in control. Cathelicidin and IL-10 levels were only higher in HD patients. IL-6 serum levels were positively correlated with all cytokines, and cathelicidin was negatively correlated with MCP-1 (r = - 0.35; p < 0.01) and positively correlated with IL-10 (r = 0.37; p = 0.001). These results suggest that a uremic environment induces high TLR4, cathelicidin and cytokine expression and may increase inflammation. Thus, future studies should be conducted to evaluate whether TLR4 and cathelicidin should be targets for anti-inflammatory therapeutic strategies.

Effects of spermidine and p-cresol on polymorphonuclear cell apoptosis and function.

Polymorphonuclear leukocytes (PMNs) from chronic kidney disease (CKD) patients display accelerated apoptosis and dysfunction, which may predispose CKD patients to infections. In this study, we investigated the effect of spermidine and p-cresol on apoptosis and function on PMN from healthy subjects. We measured the effect of spermidine and p-cresol on apoptosis, ROS production unstimulated and stimulated (S. aureus and PMA) and expression of CD95, caspase 3, and CD11b on PMN. After incubation with p-cresol and spermidine, we did not observe any changes in apoptosis, viability or expression of caspase 3 and CD95 in PMN from healthy subjects. PMN incubated for 10 minutes with spermidine demonstrated a significant reduction in spontaneous, S. aureus and PMA-stimulated ROS production. p-cresol induced a decrease in PMA-stimulated ROS production. Spermidine and p-cresol also induced a decrease in the expression of CD11b on PMN. Spermidine and p-cresol decreased the expression of CD11b and oxidative burst of PMN from healthy subjects and had no effect on PMN apoptosis and viability.

Impact of cardiovascular calcification in nondialyzed patients after 24 months of follow-up.

BACKGROUND AND OBJECTIVES: Coronary artery calcification (CAC) is highly prevalent among patients with chronic kidney disease (CKD), and it has been described as a strong predictor of mortality in the dialysis population. Because there is a lack of information regarding cardiovascular calcification and clinical outcomes in the earlier stages of the disease, we aimed to evaluate the impact of CAC on cardiovascular events, hospitalization, and mortality in nondialyzed patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a prospective study including 117 nondialyzed patients with CKD (age, 57 +/- 11.2 years; 61% male; 23% diabetics; creatinine clearance, 36.6 +/- 17.8 ml/min per 1.73 m(2)). CAC was quantified by multislice computed tomography. The occurrence of cardiovascular events, hospitalization, and death was recorded over 24 months. RESULTS: CAC >10 Agatston units (AU) was observed in 48% of the patients [334 (108 to 858.5) AU; median (interquartiles)], and calcification score >or=400 AU was found in 21% [873 (436-2500) AU]. During the follow-up, the occurrence of 15 cardiovascular events, 19 hospitalizations, and 4 deaths was registered. The presence of CAC >10 AU was associated with shorter hospitalization event-free time and lower survival. CAC >or=400 AU was additionally associated with shorter cardiovascular event-free time. Adjusting for age and diabetes, CAC >or=400 AU was independently associated with the occurrence of hospitalization and cardiovascular events. CONCLUSIONS: Cardiovascular events, hospitalization, and mortality were associated with the presence of CAC in nondialyzed patients with CKD. Severe CAC was a predictor of cardiovascular events and hospitalization in these patients.

Effect of phosphate binders on oxidative stress and inflammation markers in hemodialysis patients.

It has been suggested that phosphate binders may reduce the inflammatory state of hemodialysis (HD) patients. However, it is not clear whether it has any effect on oxidative stress. The objective of this study was to evaluate the effect of sevelamer hydrochloride (SH) and calcium acetate (CA) on oxidative stress and inflammation markers in HD patients. Hemodialysis patients were randomly assigned to therapy with SH (n=17) or CA (n=14) for 1 year. Before the initiation of therapy (baseline) and at 12 months, we measured in vitro reactive oxygen species (ROS) production by stimulated and unstimulated polymorphonuclear neutrophils and serum levels of tumor necrosis factor alpha, interleukin-10, C-reactive protein, and albumin. There was a significant reduction of spontaneous ROS production in both groups after 12 months of therapy. There was a significant decrease of Staphylococcus aureus stimulated ROS production in the SH group. There was a significant increase in albumin serum levels only in the SH group. In the SH group, there was also a decrease in the serum levels of tumor necrosis factor alpha and C-reactive protein. Our results suggest that compared with CA treatment, SH may lead to a reduction in oxidative stress and inflammation. Therefore, it is possible that phosphate binders exert pleiotropic effects on oxidative stress and inflammation, which could contribute toward decreasing endothelial injury in patients in HD.

Estimativa de ingestão protéica de pacientes em hemodiálise comparação entre registro alimentar e equivalente protéico deaparecimento de nitrogênio (pna) / Estimation of protein intake of hemodialysis patients comparison between food record and protein equivalent ofnitrogen appearance (pna)

Introdução: A avaliação do consumo alimentar, particularmente da ingestão de proteínas, constitui uma ferramenta importante na prevenção, tratamento emonitoramento da desnutrição nos pacientes em hemodiálise. Para tanto, os métodos mais comumente utilizados na prática clínica são o registro alimentar eo equivalente protéico do aparecimento de nitrogênio (PNA). Objetivo: Avaliar a concordância entre o registro alimentar e o PNA para a estimativa da ingestãoprotéica nos pacientes em hemodiálise. Casuística e Métodos: Foram estudados 39 pacientes (67% homens, 46,8±14,7anos, IMC 23,5±4,6kg/m2) emtratamento hemodialítico. Os critérios de exclusão foram presença de doenças catabólicas, função renal residual e uso de glucocorticóides. O registro alimentarfoi preenchido durante três dias e o PNA foi calculado conforme recomendado pelo NKF-DOQI. Resultados: A ingestão protéica obtida pelo registro alimentarfoi menor que aquela obtida pelo PNA (56,3±23,4 vs 67,9±23,9g/dia, respectivamente; P≤0,001). Os métodos apresentaram uma boa correlação (r=0,54;P<0,001), porém uma grande variabilidade individual foi observada (-51,7 a +28,5g/dia). A ingestão protéica obtida por ambos os métodos correlacionou-sepositivamente com o IMC (registro alimentar: r=0,41 e PNA r=0,80; P<0,05). A diferença entre os métodos (registro alimentar - PNA) correlacionou-senegativamente com o IMC (r=-0,49; P<0,01). A análise por subgrupos de IMC mostrou que o registro alimentar subestimava a ingestão protéica em relação aoPNA apenas nos pacientes com IMC≥25kg/m2. A regressão linear múltipla apontou o IMC≥25kg/m2 como único fator independentemente associado àsvariações entre os métodos. [β =-16,9 (-31,1 a -2,8); P=0,02] Conclusão: O método do registro alimentar exibiu valores menores de proteínas em relação aométodo do PNA nos pacientes em hemodiálise, sendo a condição de sobrepeso/obesidade um importante determinante destas variações.

Introduction: The assessment of food consumption, particularly of protein intake, constitutes an important tool in the prevention, treatment, and monitoringof malnutrition in hemodialysis patients. Food record and protein equivalent of nitrogen appearance (PNA) are the most commonly used methods for suchpurpose in the clinical practice. Aim: To evaluate the agreement between food record and PNA for the assessment of protein intake in hemodialysis patients.Subjects and Methods: Thirty-nine hemodialysis patients (67% male, 46.8 ± 14.7 years old, BMI 23.5 ± 4.6 kg/m2) were studied. The exclusion criteriawere catabolic illnesses, residual renal function and use of glucocorticoids. Food intake was recorded 3 days and PNA was calculated as proposed by theNKF-DOQI. Results: The protein intake assessed by food record was lower than that obtained by PNA (56.3 ± 23.4 vs 67.9 ± 23.9 g/day, respectively;P≤0.001). The methods were well correlated (r=0.54; P<0.001), however, a large individual variability was observed (-51.7 to +28.5 g/day). The protein intakeobtained by both methods correlated positively with BMI (food record: r=0.41 and PNA: r=0.80; P<0.05). The difference between the methods (food record,PNA) correlated negatively with BMI (r=-0.49; P<0.001). The analysis by subgroups of BMI showed that the food record method underestimated proteinintake in relation to PNA only in patients with BMI ≥25kg/m2. The multiple linear regression analysis pointed to BMI ≥25kg/m2 as a factor independentlyassociated with variations between the methods. Conclusion: The food record method showed lower values of protein in comparison with the PNA methodin hemodialysis patients, and overweight/obesity status was an important determinant of these variations.

Impact of dialyzer membrane on apoptosis and function of polymorphonuclear cells and cytokine synthesis by peripheral blood mononuclear cells in hemodialysis patients.

In an in vivo crossover trial, we compared a cellulosic with a synthetic dialyzer with respect to polymorphonuclear cells (PMN) function and apoptosis, cytokine serum levels and synthesis by peripheral blood mononuclear cells (PBMC), and complement activation. Twenty hemodialysis (HD) patients were assigned in alternate order to HD with cellulose acetate (CA) or polysulfone (PS) dialyzer. After 2 weeks, patients were crossed over to the second dialyzer and treated for another 2 weeks. Apoptosis was assessed by flow cytometry in freshly isolated PMN. Phagocytosis and production of peroxide by PMN were studied by flow cytometry in whole blood. PBMC were isolated from blood samples and incubated for 24 h with or without lipopolysaccharide (LPS). There was no impact of dialyzer biocompatibility on PMN apoptosis and function, cytokine synthesis by PBMC or on their serum levels, serum levels of C3a, and terminal complement complex (TCC). Nevertheless, after HD, serum levels of complement correlated negatively with PMN phagocytosis and peroxide production, and positively with PMN apoptosis and cytokine production by PBMC. Although the results did not show a dialyzer advantage on the immunologic parameters, complement activation may have modulated cell function and apoptosis after HD.

Serum and cellular interleukin-6 in haemodialysis patients: relationship with energy expenditure.

BACKGROUND: Inflammation is a highly prevalent condition among end-stage renal disease (ESRD) patients and it has been implicated with several metabolic derangements. Considering the harmful effect of hypermetabolism on nutritional status and clinical outcomes of ESRD patients, we aimed to investigate the relationship between proinflammatory cytokine interleukin-6 (IL-6) and energy expenditure in this population. METHODS: This cross-sectional study enrolled 80 adult haemodialysis patients for the evaluation of serum IL-6 and energy expenditure. The production of IL-6 by peripheral blood mononuclear cells (PBMCs) (spontaneous and endotoxin-stimulated production) was examined in a subgroup of 30 haemodialysis patients and in 11 healthy control subjects. IL-6 was measured by immunoenzymatic assay. The resting energy expenditure was evaluated by means of indirect calorimetry. Body composition was assessed by bioelectrical impedance analysis and skinfold thicknesses. RESULTS: Serum IL-6 [6.3 (2.2-163.5) pg/ml] correlated positively with age (R = 0.26; P = 0.02) and C-reactive protein (R = 0.31; P < 0.01). Resting energy expenditure correlated positively with lean body mass (R = 0.68; P < 0.001) and BMI (R = 0.44; P < 0.001), and negatively with Kt/V (R = -0.37; P < 0.01). In the multivariate analysis, controlling for age and lean body mass, serum IL-6 was positively associated with resting energy expenditure (n = 80; beta = 2.4; P = 0.01). The production of IL-6 by PBMCs did not reach statistically significant differences between patients and controls [spontaneous production 6541 (96-7739) pg/ml vs 3410 (50-7806) pg/ml, respectively; and stimulated production 6530 (579-7671) pg/ml vs 5304 (1527-7670) pg/ml, respectively]. IL-6 secreted by monocytes showed no association with either serum IL-6 or resting energy expenditure. CONCLUSION: Serum IL-6 was associated with an increase of energy expenditure in haemodialysis patients.

Dialysis care, cardiovascular disease, and costs in end-stage renal disease in Brazil.

OBJECTIVES: This study evaluates the cost of dialysis care in Brazil, including costs of ambulatory care and hospital admissions due to all causes and cardiovascular events. METHODS: Data were analyzed for 200 patients with end-stage renal disease (ESRD) on chronic hemodialysis in Brazil between 2001 and 2004. Main end points were all-cause mortality, all-cause hospital admissions, and cardiovascular events. Direct costs of dialysis treatment and complications were computed from the perspective of two payers, the Ministry of Health (MoH) and private health insurance (PHI). RESULTS: Mean number of days of hospitalization was 12 per patient-year. There were 105 cardiovascular events; the most frequent events were coronary disease (n = 59, 56 percent) and congestive heart failure (n = 26, 25 percent). The rate of cardiovascular events was 193 per 1,000 patient-years. There were 43 deaths, and the death rate was 79 per 1,000 patient-years. Median cost per hospital admission was US$ 675 and US$ 932 from the perspective of the MoH and PHI. For admissions due to cardiovascular causes, the corresponding costs were US$ 1,639 and US$ 4,499, respectively. Mean global cost per patient-year for chronic hemodialysis therapy was US$ 7,980 and US$ 13,428 from the perspective of the MoH and PHI, respectively. CONCLUSIONS: Patients on chronic hemodialysis care incur significant healthcare resources due to the costs of dialysis and complications, notably cardiovascular disease. New disease management programs aimed at reducing cardiovascular morbidity and efficient use of resources are critical to ensuring the sustainability of treatments for ESRD in Brazil.

Resting energy expenditure in peritoneal dialysis patients.

OBJECTIVES: This study aimed to evaluate whether resting energy expenditure (REE) of patients undergoing peritoneal dialysis (PD) therapy differs from that of healthy individuals, as well as to investigate the factors associated with REE in this sample of patients. DESIGN: Cross-sectional study. SETTING: Dialysis Unit of the Nephrology Division, Federal University of Sao Paulo-Oswaldo Ramos Foundation, Brazil. SUBJECTS AND METHODS: The study examined the REE of 37 patients (20 males, age 44.5 +/- 13 years) undergoing PD therapy. Only patients older than 18 years, on PD for at least 3 months, without catabolic illness, and with normal thyroid function were included. Patients were pair matched for age and gender with 37 healthy individuals. REE was measured by indirect calorimetry. Body composition was assessed by dual-energy x-ray absorptiometry in the patients and by bioelectrical impedance in the healthy individuals. RESULTS: The REE of PD patients was similar to that of pair-matched controls (1372 +/- 266 and 1453 +/- 252 kcal/day respectively, p = 0.13) even when adjusted for lean body mass and gender (p = 0.56). The REE of PD patients was positively correlated with lean body mass (r = 0.60, p < 0.01), fat mass (r = 0.43, p < 0.01), body mass index (r = 0.60, p < 0.01), serum glucose (r = 0.36, p < 0.05), and protein equivalent of nitrogen appearance (PNA; r = 0.42, p < 0.01). There were no correlations between REE and glucose absorption, dialysis-related parameters, C-reactive protein, and energy or protein intake by 3-day food diary. In the multiple linear regression analysis, using REE as the dependent variable, the final model showed that lean body mass and female gender were determinants of REE in PD patients (R(2) = 0.44). When separate analysis by gender was performed, REE correlated directly with body fat in female patients (r = 0.70, p < 0.01) but not in male patients (r = 0.29, p = 0.21). On the other hand, lean body mass was significantly correlated with REE in male patients (r = 0.78, p < 0.01) but not in female patients (r = 0.47, p = 0.06). CONCLUSIONS: This study showed that REE of PD patients did not differ from that of healthy individuals. The strong association between body fat and REE in female patients remains to be further investigated.

Effect of temporary catheter and late referral on hospitalization and mortality during the first year of hemodialysis treatment.

Late referral (LR) to dialysis therapy has been associated with poor outcomes in people with end-stage renal disease. This had been ascribed to the frequent use of temporary vascular catheters (TVCs) in LR patients. The effects of LR and TVC on the outcomes of an incident hemodialysis population (n = 101) were investigated. There was a higher incidence of vascular access infection, longer period of hospitalization, and lower survival in TVC and LR groups, compared with arteriovenous fistula and early referral (ER) groups, respectively. Late referral patients had higher number of hospitalizations than ER patients. In univariate analysis, LR (hazard ratio [HR] 10.8, P = 0.02) and albumin (HR 0.23, P < 0.0001) were associated with mortality. Late referral and body mass index were associated with the increased risk of hospitalization in univariate analysis. In multivariate analysis, LR was the only risk factor associated with hospitalization (HR 3.51, P = 0.002). In conclusion, LR was associated with increased risk of mortality and increased risk of hospitalization independently of the presence of a TVC.