Chronic kidney disease-associated pruritus (CKD-aP) is associated with worse quality of life and increased healthcare utilization among dialysis patients.

PURPOSE: Chronic pruritus significantly impairs hemodialysis patients' health status and quality of life (QOL) and it is associated with higher mortality rate, more frequent hospitalizations, poorer dialysis and medication adherence, and deteriorated mental status. However, pruritus is still underestimated, underdiagnosed, and undertreated in the real-life clinical scenario. We investigated prevalence, clinical characteristics, clinical correlates, severity as well as physical and psychological burden of chronic pruritus among adult hemodialysis patients in a large international real-world cohort. METHODS: We conducted a retrospective cross-sectional study of patients registered in 152 Fresenius Medical Care (FMC) NephroCare clinics located in Italy, France, Ireland, United Kingdom, and Spain. Demographic and medical data were retrieved from the EuCliD® (European Clinical) database, while information on pruritus and QoL were abstracted from KDQOL™-36 and 5-D Itch questionnaire scores. RESULTS: A total of 6221 patients were included, of which 1238 were from France, 163 Ireland, 1469 Italy, 2633 Spain, and 718 UK. The prevalence of mild-to-severe pruritus was 47.9% (n = 2977 patients). Increased pruritus severity was associated with increased use of antidepressants, antihistamines, and gabapentin. Patients with severe pruritus more likely suffered from diabetes, more frequently missed dialysis sessions, and underwent more hospitalizations due to infections. Both mental and physical QOL scores were progressively lower as the severity of pruritus increased; this association was robust to adjustment for potential confounders. CONCLUSION: This international real-world analysis confirms that chronic pruritus is a highly prevalent condition among dialysis patients and highlights its considerable burden on several dimensions of patients' life.

The Cardiovascular Literature-Based Risk Algorithm (CALIBRA): Predicting Cardiovascular Events in Patients With Non-Dialysis Dependent Chronic Kidney Disease.

Background and Objectives: Cardiovascular (CV) disease is the main cause of morbidity and mortality in patients suffering from chronic kidney disease (CKD). Although it is widely recognized that CV risk assessment represents an essential prerequisite for clinical management, existing prognostic models appear not to be entirely adequate for CKD patients. We derived a literature-based, naïve-bayes model predicting the yearly risk of CV hospitalizations among patients suffering from CKD, referred as the CArdiovascular, LIterature-Based, Risk Algorithm (CALIBRA). Methods: CALIBRA incorporates 31 variables including traditional and CKD-specific risk factors. It was validated in two independent CKD populations: the FMC NephroCare cohort (European Clinical Database, EuCliD®) and the German Chronic Kidney Disease (GCKD) study prospective cohort. CALIBRA performance was evaluated by c-statistics and calibration charts. In addition, CALIBRA discrimination was compared with that of three validated tools currently used for CV prediction in CKD, namely the Framingham Heart Study (FHS) risk score, the atherosclerotic cardiovascular disease risk score (ASCVD), and the Individual Data Analysis of Antihypertensive Intervention Trials (INDANA) calculator. Superiority was defined as a ΔAUC>0.05. Results: CALIBRA showed good discrimination in both the EuCliD® medical registry (AUC 0.79, 95%CI 0.76-0.81) and the GCKD cohort (AUC 0.73, 95%CI 0.70-0.76). CALIBRA demonstrated improved accuracy compared to the benchmark models in EuCliD® (FHS: ΔAUC=-0.22, p<0.001; ASCVD: ΔAUC=-0.17, p<0.001; INDANA: ΔAUC=-0.14, p<0.001) and GCKD (FHS: ΔAUC=-0.16, p<0.001; ASCVD: ΔAUC=-0.12, p<0.001; INDANA: ΔAUC=-0.04, p<0.001) populations. Accuracy of the CALIBRA score was stable also for patients showing missing variables. Conclusion: CALIBRA provides accurate and robust stratification of CKD patients according to CV risk and allows score calculations with improved accuracy compared to established CV risk scores also in real-world clinical cohorts with considerable missingness rates. Our results support the generalizability of CALIBRA across different CKD populations and clinical settings.

Blood pressure variability and cardiovascular autonomic control during hemodialysis in peripheral vascular disease patients.

Hemodialysis (HD) patients with peripheral vascular disease (PVD) are at higher risk of mortality. The main objectives of this work were to investigate the hypothesis of an association between the PVD and an altered control system on peripheral resistance in response to volume depletion induced by HD treatment; and to investigate whether HD induced increase of pulse pressure (PP) is associated with PVD. Continuous blood pressure (BP) was recorded during HD treatment at the beginning and at the end of HD. The overhydration condition was evaluated by means of whole body bioimpedance spectroscopy, measured before each HD treatment. BP variability, heart rate variability and baroreflex sensitivity were then analyzed. Patients affected by PVD reported a prevalence of peripheral local control as shown by higher values of very low frequency in diastolic blood pressure (DBP) variability and a reduced cardiac baroreflex with respect to patients not affected by this pathology. HD treatment induced a significant increase of PP and LF% in DBP series in PVD patients only. Our results suggested that differences in BP variability and PP changes could be related not only to an underlying vascular disease, but also to an alteration in autonomic control.

Novel image processing methods for the analysis of calcium dynamics in glial cells.

Calcium (Ca(2+)) waves and Ca(2+) oscillations within cells initiate a wide range of physiological processes including control of cell signaling, gene expression, secretion, and cell migration. A thorough analysis of Ca(2+) waves in glial cells provides information not only about the subcellular location of signaling processing events but also about nonneuronal or intercellular signaling pathways, their timing, routes, spatial domains, and coordination. In this study, three novel image processing methods have been applied to the study of Ca(2+) dynamics in cells. These bring additional information to the methods already available in the literature, providing insight into the analysis of calcium dynamics in fluorescence recordings and defining bidimensional maps that give a complete and detailed description of calcium intracellular behavior. The application of these processing methods to glial cells highlighted the complex 2-D Ca(2+) dynamics phenomena, the location of calcium uptake and release microdomains on the endoplasmic reticulum, and the correlation between different calcium signals inside the cell. A perinuclear zone acting as a filter and regulator of intracellular calcium waves was detected: it acts as a controller of calcium fluxes between the cytoplasm and the nucleus.

Alteration of autonomic blood pressure control during hemodialysis in peripheral vascular disease patients.

Blood pressure (BP) response to volume depletion induced by hemodialysis (HD) treatment may be important to understand the pathophysiology of the increased mortality in HD patients with vascular calcification. In the present study a comparison between end stage renal disease (ESRD) patients affected by peripheral vascular disease (PVD) and ESRD patients without PVD was performed. Continuous blood pressure was recorded at the beginning and at the end of HD. BP and heart rate variability (HRV) were analyzed to quantify the autonomic nervous system regulation of heart beat and peripheral resistance. PVD patients showed an increase of pulse pressure (PP) during HD, an altered autonomic peripheral control, a lower sympathetic activity, with respect to ESRD patients without PVD.