Patients' experience one year after dialysis initiation: a lexicometric analysis

Background Dialysis implies huge changes in patients' lives. Yet, there is a need to better understand patients' experience in the time following dialysis initiation. Objective The objective of this study was to investigate patients' experience of dialysis a year after treatment initiation and the associations between patients' discourse and their anxiety and depression symptoms. Methods Twenty two patients (mean age 63.4; 68% men) took part in a semi-directed interview about their experience with dialysis. Participants completed the Hospital Anxiety and Depression Scale (HADS). Interviews were analyzed using a lexicometric analysis. Results The analysis generated five classes: experience with nephrological care, facing loss and family relationships, family and acceptance, implementation of a new routine and making sense of the end-stage renal disease experience. Patients' felt very passive in their experience with care. They reported the importance of integrating dialysis in their lives and the role of family support when facing treatment initiation. Depressed patients were more likely to describe their nephrological monitoring very factually and to talk about what they lost with dialysis initiation. Conclusion Dialysis initiation is a hard time for patients during which they face many challenges. This first year represents a time of adaptation, in which family seems essential

Nutrition in hemodialysis patients previously on a supplemented very low protein diet

Nutrition in hemodialysis patients previously on a supplemented very low protein diet.BackgroundNutritional safety of protein-restricted diets in patients with chronic renal failure is controversial. In the present study, we have assessed the evolution of nutritional status after initiation of hemodialysis in patients previously treated by a supplemented very low protein diet (SVLPD).MethodsNutritional data were prospectively collected during the first year of hemodialysis from 15 consecutive patients treated with a SVLPD (0.3 g protein/kg/day supplemented with essential amino acids, calcium, iron, and vitamins) and compared to 15 age- and gender-matched end-stage renal disease (ESRD) patients previously on a less-restricted diet (0.90 ± 0.21 g protein/kg/day) who started hemodialysis during the same period. Dual-energy x-ray absorptiometry (DEXA) was used to assess body composition at 0, 6, and 12 months. Hemodialysis prescriptions, biologic data and 3-day food records were collected every 3 months.ResultsProtein intake was higher than 1.2 g/kg/day in both groups as soon as 3 months after the start of hemodialysis. Albumin and prealbumin increased significantly during the first 6 months in all patients. Body mass index (BMI) increased in all patients (+0.97 ± 1.31 kg/m2; P < 0.001) reflecting a gain in fat mass in the overall population (+2.36 ± 2.94 kg/m2; P < 0.001) while lean body mass remained stable overall.ConclusionOnce on hemodialysis, SVLPD patients rapidly increased protein intake. Nutritional status improved in all patients, with a gain in fat mass in all, and a gain in lean body mass in SVLPD men only. These data indicate that treatment with a SVLPD prior to hemodialysis initiation is nutritionally safe

CD154 Induces Interleukin-6 Secretion by Kidney Tubular Epithelial Cells under Hypoxic Conditions: Inhibition by Chloroquine

Funder: MSDAvenirInflammation is a major contributor to tubular epithelium injury in kidney disorders, and the involvement of blood platelets in driving inflammation is increasingly stressed. CD154, the ligand of CD40, is one of the mediators supporting platelet proinflammatory properties. Although hypoxia is an essential constituent of the inflammatory reaction, if and how platelets and CD154 regulate inflammation in hypoxic conditions remain unclear. Here, we studied the control by CD154 of the proinflammatory cytokine interleukin- (IL-) 6 secretion in short-term oxygen (O2) deprivation conditions, using the HK-2 cell line as a kidney tubular epithelial cell (TEC) model. IL-6 secretion was markedly stimulated by CD154 after 1 to 3 hours of hypoxic stress. Both intracellular IL-6 expression and secretion were stimulated by CD154 and associated with a strong upregulation of IL-6 mRNA and increased transcription. Searching for inhibitors of CD154-mediated IL-6 production by HK-2 cells in hypoxic conditions, we observed that chloroquine, a drug that has been repurposed as an anti-inflammatory agent, alleviated this induction. Therefore, CD154 is a potent early stimulus for IL-6 secretion by TECs in O2 deprivation conditions, a mechanism likely to take part in the deleterious inflammatory consequences of platelet activation in kidney tubular injury. The inhibition of CD154-induced IL-6 production by chloroquine suggests the potential usefulness of this drug as a therapeutic adjunct in conditions associated with acute kidney injury

A statistically inferred microRNA network identifies breast cancer target miR-940 as an actin cytoskeleton regulator

International audienceMiRNAs are key regulators of gene expression. By binding to many genes, they create a complex network of gene co-regulation. Here, using a network-based approach, we identified miRNA hub groups by their close connections and common targets. In one cluster containing three miRNAs, miR-612, miR-661 and miR-940, the annotated functions of the co-regulated genes suggested a role in small GTPase signalling. Although the three members of this cluster targeted the same subset of predicted genes, we showed that their overexpression impacted cell fates differently. miR-661 demonstrated enhanced phosphorylation of myosin II and an increase in cell invasion, indicating a possible oncogenic miRNA. On the contrary, miR-612 and miR-940 inhibit phosphorylation of myosin II and cell invasion. Finally, expression profiling in human breast tissues showed that miR-940 was consistently downregulated in breast cancer tissues M icroRNAs are a class of endogenous, small (19–25 nucleotides), single-stranded non-coding RNAs that regulate gene expression in all eukaryotic organisms. In metazoans, microRNAs most commonly bind to the 39 untranslated region (39UTR) of their mRNA target transcript and cause translational repression and/or mRNA degradation. Every microRNA is predicted to regulate from a dozen to thousands of genes, including transcription factors. This fine-tuning of protein expression is known to be involved in many physiological processes, such as development, apoptosis, signal transduction and even cancer progression 1,2. More than 2,000 mature human microRNAs are listed in the 20 th release of miRBase: http://www.mirbase.org (2014) (Date of access:19/08/2013), and some authors hypothesise that the majority of human genes are regulated by microRNAs 3. Since their discovery in 1993 4 , a fair understanding of their role in animal development and in the onset and progression of diseases 2 , as well as of their potential use in therapies 5 , has been gathered. However, the cooperative behaviour of microRNAs is still under investigation. A growing body of experimental evidence suggests that microRNAs can regulate genes through complementarity, meaning that microRNAs can act together to regulate individual genes or groups of genes involved in similar processes 6. For example, Hu and co-workers demonstrated that transducing a cocktail of precursor microRNAs (miR-21, miR-24 and miR-221) can result in more effective engraftment of transplanted cardiac progenitor cells 7. Consistent with these discoveries, Zhu et al. demonstrated that miR-21 and miR-221 coregulate 56 gene ontology (GO) processes 8. In the same study, the authors also showed that cotransfection of miR-1 and miR-21 increases H 2 O 2-induced myocardial apoptosis and oxidative stress. These recent findings support the idea of microRNA-mediated cooperative regulation but also argue for the use of systemic approaches, notably based on graph theory, to decipher individual and complementary roles of microRNAs. Some work has been conducted to use recent high-throughput experiment-derived data sets to infer microRNA synergistic relationships 9–12. Herein, we present a microRNA network based on target similarities among microRNAs to infer clusters of microRNAs. Clusters are defined as groups of microRNAs sharing a set of common targets, predicted by either DIANA-microT v3 13 or TargetScan v6.2 14. Some authors have used GO enrichment analysis as a confirmatory tool for their clustering approach 11. In our case, GO enrichment is not used to infer networks but as a way to estimate the probable metabolic pathway(s) a cluster of microRNAs could co-regulate. Moreover, the novelty of our approach is to consider not only clusters of microRNAs but also OPE

Improvement of leucocytic Na+K+ pump activity in uremic patients on low protein diet

Improvement of leucocytic Na+ K+ pump activity in uremic patients on low protein diet. Leucocytic Na+K+ pump activity was assessed in 20 patients with advanced renal failure. Na+K+-ATPase activity was reduced when compared with the values obtained from normal subjects (101.8 ± 48.6 versus 165.13 ± 8.9 µM of Pi hr-1 · g-1 P < 0.001) and the mean 86Rb uptake by U 937 cells was depressed by 38% after the addition of patients' sera. Subsequently, patients were put on a diet providing 0.3g protein/kg body weight daily and supplemented with ketoacids. After three months of dietary treatment Na+K+-ATPase activity increased to 142 ± 48.3 (P < 0.01) and reached normal values at the sixth month (162.8 ± 54.70 µM of Pi hr-1 · g-1; P < 0.001) whereas 86Rb uptake increased by 23 percent when compared to initial values. These data suggest that among the different mechanisms which have been advanced to explain the defects in the Na+ pump observed in uremic patients, circulating inhibitors deriving from alimentary protein intake may affect cation transport

Risk-based individualisation of target haemoglobin in haemodialysis patients with renal anaemia in the post-TREAT era: theoretical attitudes versus actual practice patterns (MONITOR-CKD5 study)

Purpose: Data from an ongoing European pharmacoepidemiological study (MONITOR-CKD5) were used to examine congruence between physician-reported risk-based individualisation of target haemoglobin (Hb) and the actual Hb targets set by these physicians for their patients, as well as actual Hb levels in their patients. Methods: Physician investigators participating in the study completed a questionnaire about their anaemia practice patterns and attitudes post-TREAT at the start of the study (T1) and in summer 2013 (T2). These data were compared with the Hb targets identified at baseline for actual patients (n&nbsp;=&nbsp;1197) enrolled in the study. Risk groups included presence/absence of hypertension, diabetes, cardiovascular complications, history of stroke, history of cancer, and age/activity level (elderly/inactive or young/active). Results: At each time point, more than three quarters of physicians responded that results from the TREAT study, in patients not on dialysis, have influenced their use of erythropoiesis-stimulating agents in patients on haemodialysis. At T1, there was a clear difference in physician-reported (theoretical) target Hb levels for patients across the different risk groups, but there was no difference in patients’ actual Hb levels across the risk groups. A similar disparity was noted at T2. Conclusions: Physicians’ theoretical attitudes to anaemia management in patients on haemodialysis appear to have been influenced by the results of the TREAT study, which involved patients not on dialysis. Physicians claim to use risk-based target Hb levels to guide renal anaemia care. However, there is discrepancy between these declared risk-based target Hb levels and actual target Hb levels for patients with variable risk factors

Guideline attainment and morbidity/mortality rates in a large cohort of European hemodialysis patients (EURODOPPS)

International audienceBackground. Haemodialysis patients experience a wide variety of intermediate complications, such as anaemia, hypertension and mineral bone disease (MBD). We aimed to assess the risk of death and hospital admissions as a function of the simultaneous attainment of different guideline targets (for hypertension, anaemia andMBD) in a large European cohort of dialysis patients. Methods. EURODOPPS is part of the Dialysis Outcomes and Practice Patterns Study (DOPPS) international, prospective cohort study of adult, in-centre haemodialysis patients for whom clinical data are extracted from medical records. In the present analysis, 6317 patients from seven European countries were included between 2009 and 2011. The percentages of patients treated according to the international guidelines on anaemia, hypertension and MBD were determined. The overall degree of guideline attainment was considered to be high if four or all five of the evaluated targets were attained, moderate if two or three targets were attained, and low if fewer than two targets were attained. Fully adjusted multivariate Cox models were used to investigate the relationship of target attainment with mortality and first hospital admission. Results. At baseline, the degree of target attainment was low in 1751 patients (28%), moderate in 3803 (60%) and high in 763 (12%). In the fully adjusted model using time-dependent covariates, low attainment was associated with higher all-cause mortality [hazard ratio (95% confidence interval) = 1.19 (1.05-1.34)] and high attainment was associated with lower all-cause mortality [0.82 (0.68-0.99)]. In a similarmodel that additionally accounted for death as a competing risk, low and high attainments were not associated with hospital admission. Conclusion. In a large international cohort of dialysis patients, we have shown that more stringent application of guidelines is associated with lower mortality

Prescription of reninâ angiotensinâ aldosterone system inhibitors (RAASi) and its determinants in patients with advanced CKD under nephrologist care

Reninâ angiotensinâ aldosterone system inhibitors (RAASi) are recommended for chronic kidney disease (CKD) patients. In this study, we describe RAASi prescription patterns in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) in Brazil, Germany, France, and the United States (US). 5870 patients (mean age 66â 72 years; congestive heart failure [CHF] in 11%â 19%; diabetes in 43%â 54%; serum potassium â ¥5 in 20%â 35%) were included. RAASi prescription was more common in Germany (80%) and France (77%) than Brazil (66%) and the United States (52%), where the prevalence of prescription decreases particularly in patients with CKD stage 5. In the multivariable regression model, RAASi prescription was least common in the United States and more common in patients who were younger, had diabetes, hypertension, or less advanced CKD. In conclusion, RAASi prescription patterns vary by country, and by demographic and clinical characteristics. RAASi appear to be underused, even among patients with strong classâ specific recommendations. Although the reasons for this variation could not be fully identified in this crossâ sectional observation, our data indicate that the risk of hyperkalemia may contribute to the underuse of this class of agents in moderate to advanced CKD.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150590/1/jch13563.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150590/2/jch13563_am.pd