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Background: Soluble transferrin receptor (sTfR) is a biomarker of erythropoiesis, which is often impaired in dialysis patients. The aim of our study was to evaluate sTfR levels in chronically dialyzed patients and assess potential determinants of its levels. Methods: We performed a cross-sectional study by evaluating 246 end-stage renal disease patients undergoing dialysis and 32 healthy controls. Circulating levels of interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, hepcidin, sTfR, growth differentiation factor 15 (GDF15), and traditional iron metabolism markers were measured, as well as hemogram parameters. Clinical data was obtained from all patients. Results: Compared to controls, patients presented similar values of sTfR, reticulocytes and reticulocyte production index (RPI), and significantly higher levels of IL-6, CRP, ferritin, hepcidin, TNF-α, and GDF15. Iron, transferrin, hemoglobin levels, erythrocyte count, mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) values were significantly lower in dialysis group. Within patients, sTfR values were higher in diabetic patients and were positively and significantly correlated with reticulocytes and erythrocytes, RPI, and therapeutic doses of erythropoiesis stimulating agents (ESA) and intravenous iron; and inversely and significantly correlated with circulating iron, ferritin, transferrin saturation, hepcidin, MCH, and MCHC. In multiple linear regression analysis, ESA dose, RPI, serum iron, diabetes, and hepcidin levels were independently associated with sTfR levels in dialysis patients and, thus, with erythropoiesis. Conclusion: Our data suggest that, besides RPI and ESA dose, diabetes and hepcidin are closely related to erythropoiesis in dialysis patients. The influence of diabetes on sTfR levels deserves further investigation. [ABSTRACT FROM AUTHOR]

Non-adherence to medical plans is recognized as an important problem in dialysis patients, since it has been associated with increased morbidity and mortality, resulting in disproportionately high costs of care. The success of renal replacement therapy depends on the adherence of patients to the different aspects of the therapeutic strategy, which includes a complex drug regimen involving a wide variety of drugs and doses, several prescribed dialysis sessions with different durations, dietetic recommendations and restriction of fluid intake. In this work, we aimed to translate and validate a previously described self-reported end-stage renal disease questionnaire (ESRD-AQ) to the Portuguese language (PESRD-AQ). After ESRD-AQ translation, a validation was performed by experts and by using a cohort of 185 Portuguese dialysis patients. PESRD-AQ reliability analysis showed strong test–retest stability across all items, with an intra-class correlation of 0.931. The average of the item-level content validity index by experts for the 46 items was 0.98, ranging from 0.94 to 1. Moreover, we found that PESRD-AQ scores indicative of non-adherence were associated with alterations in some biological and biochemical markers of non-adherence, including interdialytic weight gain. In conclusion, our results showed that PESRD-AQ, which presented an acceptable reliability and validity, is a valid tool to be used for adherence evaluation by Portuguese-speaking dialysis patients. [ABSTRACT FROM PUBLISHER]

The aim of this work was to evaluate the predictors of mortality in a group of end-stage kidney disease (ESRD) patients under dialysis, by performing a three-year follow-up study. From the 236 patients included in this study, 54 patients died during the three-year follow-up period. Our data showed that the risk of death was higher in patients presenting lower levels of mean cell hemoglobin concentration, transferrin, and albumin. Our study showed that poor nutritional status and an inflammatory-induced iron depleted erythropoiesis are important factors for mortality in these patients. [ABSTRACT FROM PUBLISHER]

The aim of this work was to contribute to a better understanding of the relationship between resistance to recombinant human erythropoietin (rhEPO) therapy and body mass index (BMI) in hemodialysis (HD) patients. We evaluated 191 HD patients and 25 healthy individuals. Complete blood count, reticulocyte count, and circulating levels of ferritin, transferrin, iron, soluble transferrin receptor (sTfR), transferrin saturation, hepcidin, C-reactive protein (CRP), interleukin 6 (IL-6), albumin, and adiponectin were measured in all patients and controls. Non-responder patients ( n = 16), as compared with responder patients ( n = 175), showed statistically significant lower BMI values, an enhanced inflammatory and higher adiponectin levels, associated with disturbances in iron metabolism. Analyzing the results according to BMI, we found that underweight patients required higher rhEPO doses than normal, overweight, and obese patients, and a higher percentage of non-responders patients were found within the underweight group of HD patients. Moreover, underweight patients presented lower levels of transferrin and higher levels of adiponectin compared to overweight and obese patients, and lower levels of iron compared with normal weight patients. Multiple regression analysis identified the sTfR, hemoglobin, BMI, and albumin as independent variables associated with rhEPO doses. In conclusion, our work showed that HD patients resistant to rhEPO therapy present a functional iron deficiency and a higher degree of inflammation, despite their lower BMI values and higher levels of adiponectin. Actually, BMI is poorly related with markers of systemic inflammation, such as IL-6 and CRP, while adiponectin works a fairly good indirect marker of adiposity within HD patients. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to evaluate the association of tissue-type plasminogen activator (t-PA) levels with clinical data of patients under haemodialysis (HD) and with several variables potentially related to endothelial function and dysfunction. Material and methods. In a cross-sectional study involving 189 Portuguese HD patients, circulating levels of t-PA, lipids, oxidized low-density lipoprotein (Ox-LDL), interleukin-6 (IL-6), C-reactive protein (CRP), adiponectin, plasminogen activator inhibitor type 1 (PAI-1) and fibrin fragment D-dimer were measured. Results. Considering the entire population, t-PA correlated inversely and significantly with adiponectin and high-density lipoprotein-cholesterol, and positively and significantly with age, body mass index, PAI-1, IL-6, CRP, D-dimer, cholesterol and Ox-LDL. In multiple linear regression analysis PAI-1, age and adiponectin remained statistically associated with t-PA values ( p < 0.01 for all). The weakest significant association ( p = 0.046) was that found between t-PA and D-dimer. Conclusion. Adiponectin is a main determinant of t-PA level, which may be a good marker of endothelial dysfunction in HD patients. [ABSTRACT FROM AUTHOR]

End-stage renal disease (ESRD) under hemodialyses (HD) is related with a higher propensity to infections, essentially due to T-cell lymphopenia. We postulated that HD procedure affects CD4++ T cells, especially by inducing apoptotic death and that recombinant human erythropoietin (rhEPO) therapy may also play an important role in the modulation of the immune system in these patients. T-cell phenotype and apoptosis of HD patients and healthy controls were evaluated by flow cytometry using anticoagulated whole-blood samples. In 12 HD patients, these parameters were also analyzed before and immediately after HD procedure. HD patients showed a decrease in total circulating CD3++ lymphocytes, especially in CD4++ T cells (0.747 ±± 0.410 vs. 0.941 ±± 0.216 ×× 109//L, p < 0.05), which could be a consequence of the higher proportion of CD3++ and CD4++ lymphocytes in the latest stage of apoptosis (or death) and of the higher proportion of apoptotic CD4++ T cells observed in the patients immediately after HD procedure (2.91 ±± 0.780 vs. 3.90 ±± 1.96, p < 0.05). A positive and statistically significant correlation between CD3++ and CD4++ lymphocytes in latest stage of apoptosis (or death) with HD time was found (CD3++: r == 0.592, p < 0.01; CD4++: r == 0.501, p < 0.01). We also found a negative and significant correlation between weekly rhEPO doses and the number of CD4++ T cells ( r == --0.358, p < 0.05). In conclusion, HD procedure still contributes to the development of T-cell lymphopenia, at least in part, by apoptosis induction. It was also shown that rhEPO therapy is associated with the CD4++ T-cell decline, possibly by immune modulation, eliminating atypical cells and helping to restore the CD4++ T-cell subset. [ABSTRACT FROM AUTHOR]

Our aim was to evaluate the influence of the hemodialysis (HD) procedure in red blood cells (RBC) membrane protein composition. We evaluated hematological data (RBC count, hemoglobin concentration, and hematimetric indices) and RBC membrane protein composition (linear and exponential gradient polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate [SDS-PAGE] followed by densitometry analysis of RBC membrane proteins) before and immediately after the HD procedure in 20 patients (10 responders and 10 non-responders to recombinant human erythropoietin therapy [rhEPO]) and 26 healthy controls. Before HD, patients presented anaemia and significant changes in membrane protein composition, namely, a statistically significant reduction in spectrin associated with a significant increase in bands 6, as well as an altered membrane protein interaction (protein 4.1/spectrin, protein 4.1/band 3, protein 4.2/band 3 and spectrin/band 3). After HD, we found that patients showed a statistically significant increase in RBC count and hemoglobin, a further and statistically significant decrease in spectrin, an increase in band 3, and an altered spectrin/band 3 ratio. When comparing responders and non-responders patients after HD, we found that the non-responders presented a trend to a higher reduction in spectrin. Our data suggest that HD procedure seems to contribute to a reduction in spectrin, which is normally associated with a reduction in RBC deformability, being that reduction in spectrin is higher in non-responder patients. [ABSTRACT FROM AUTHOR]