Impact of Serum Phosphate on Hemoglobin Level:A Longitudinal Analysis on a Large Cohort of Dialysis Patients

Background/Objectives:Phosphate is a macro-element involved in all cellular energetic processes. As about 90% of the phosphate filtered by the glomerulus is excreted by kidneys, the impairment of renal function and the consequent over-secretion of parathyroid hormone and fibroblast growth factor 23 results in the increase in the serum phosphate levels. The association between phosphate and hemoglobin is controversial, as both direct and indirect relationships have been reported. The present study aims to investigate the relationship between phosphate and hemoglobin in a large prospective, longitudinal cohort including dialysis patients from the Sicilian Registry of Nephrology, Dialysis, and Transplantation. Methods:In this prospective cohort study, we included 6263 hemodialysis patients to achieve a total of 120,462 repeated measurements of serum phosphate and hemoglobin over time. The longitudinal association between phosphate and hemoglobin was analyzed by univariate and multivariate Linear Mixed Models. Results: The mean age was 66 ± 16 years and the median dialysis vintage was 5 months [IQR: 2–16]. Mean and median values of hemoglobin and phosphate were 10.7 g/dL (SD 1.3 g/dL) and 4.6 mg/dL [IQR 3.9–5.5 mg/dL], respectively. The multivariate model, adjusted for potential confounders, confirmed the positive association between serum phosphate and hemoglobin [adjβ = 0.13, 95%CI 0.03–0.23, p = 0.01)]. These results were confirmed in analyses stratified for the use of phosphate binders. Conclusions: In our large cohort of dialysis patients, we found a linear, direct relationship between phosphate and hemoglobin levels. As a reduction in phosphate is associated with a parallel reduction in hemoglobin levels, hypophosphatemia can accentuate anemia in dialysis patients. Our results generate the hypothesis that monitoring serum phosphate in clinical practice might provide a better management of anemia.</p

Wearable Sensor for Real-time Monitoring of Hydrogen Peroxide in Simulated Exhaled Air

In this work, an innovative and cheap electrochemical sensor for hydrogen peroxide quantification in exhaled breath was developed. H2O2 is the most used biomarker among the Reactive Oxygen Species (ROS) for monitoring the level of oxidative stress in the respiratory system. This is due to its stability and ability to cross biological membranes and also because it is detectable in extracellular space. The electrochemical sensor was obtained using the silver layer of wasted compact discs (CDs). All three electrodes, working (WE), counter (CE), and pseudo-reference electrode (RE), were fabricated using a laser cutter. The working electrode was used directly, while an Ag/AgCl paste and a graphite paste were applied respectively on the RE and the CE. In addition, a chitosan layer was deposited by Electro-Phoretic Deposition (EPD) on the surface of the sensor. This biopolymer improves the wettability of the sensor in presence of a humid atmosphere such as that given by exhaled air. The sensor was tested in both liquid and nebulized solutions containing different concentrations of hydrogen peroxide. The detection of H2O2 was evaluated using Linear Sweep Voltammetry (LSV) as electrochemical technique. The results show that the peak current increases linearly with hydrogen peroxide concentration from 100 to 500 μM with a sensitivity of 0.068 µA µM−1 cm−2 and 0.108 µA µM−1 cm−2, a Limit Of Detection (LOD) of 60 μM and 30 μM respectively for liquid and nebulized solutions. Therefore, the use of the electrochemical sensor can allow the monitoring of hydrogen peroxide in real time with good results

Renal function decline in older men and women with advanced CKD:Results from the EQUAL study

INTRODUCTION: Understanding the mechanisms underlying the differences in renal decline between men and women may improve sex-specific clinical monitoring and management. To this end, we aimed to compare the slope of renal function decline in older men and women in chronic kidney disease (CKD) Stages 4 and 5, taking into account informative censoring related to the sex-specific risks of mortality and dialysis initiation. METHODS: The European QUALity Study on treatment in advanced CKD (EQUAL) study is an observational prospective cohort study in Stages 4 and 5 CKD patients ≥65 years not on dialysis. Data on clinical and demographic patient characteristics were collected between April 2012 and December 2018. Estimated glomerular filtration rate (eGFR) was calculated using the CKD Epidemiology Collaboration equation. eGFR trajectory by sex was modelled using linear mixed models, and joint models were applied to deal with informative censoring. RESULTS: We included 7801 eGFR measurements in 1682 patients over a total of 2911 years of follow-up. Renal function declined by 14.0% [95% confidence interval (CI) 12.9–15.1%] on average each year. Renal function declined faster in men (16.2%/year, 95% CI 15.9–17.1%) compared with women (9.6%/year, 95% CI 6.3–12.1%), which remained largely unchanged after accounting for various mediators and for informative censoring due to mortality and dialysis initiation. Diabetes was identified as an important determinant of renal decline specifically in women. CONCLUSION: In conclusion, renal function declines faster in men compared with women, which remained similar after adjustment for mediators and despite a higher risk of informative censoring in men. We demonstrate a disproportional negative impact of diabetes specifically in women

Electrochemical Detection of H2O2 for Real-Time Monitoring of Oxidative Stress

Today, the high incidence rate of fatal accidents and occupational diseases in industries is alarming. The use of safety devices and periodic health checks for workers certainly reduce the associated risks, but they are unable to monitor their condition in real-time. In recent years, the research aims to develop electrochemical sensors as an alternative to time-consuming and expensive traditional diagnostic techniques. Moreover, electrochemical sensors are generally flexible and they can be miniaturized, these properties allow their integration into wearable devices. [1] In this work, a low-cost electrochemical sensor was developed to be inserted into a mask for the detection of hydrogen peroxide in the exhaled breath in real-time. So this sensor could avoid the necessity to condensate the exhaled air for its traditional analyses [2]. In particular, hydrogen peroxide is the most used biomarker in monitoring oxidative stress due to its stability and ability to diffuse across the cell membrane. Oxidative stress occurs when the concentration of hydrogen peroxide in biological fluids increases; this condition is a risk factor for many diseases. Since oxidative stress is not associated with specific symptoms, it is important to monitor the concentration of hydrogen peroxide to prevent the onset of serious diseases or slow down their progression. [3] The low cost of this device is related to the fact that it is obtained from CDs at the end of life because their metallic layer, a thin film of silver, can be used for its electrochemical properties. In particular, the silver layer was peeled off the CD and a three electrodes configuration was given using a laser cutter [4]. Then, a graphite paste and an Ag/AgCl paste were applied to the counter and the reference electrode respectively, while the working electrode was modified with a Prussian Blue film in order to improve the electrochemical performance. In addition, a chitosan layer was electrodeposited to facilitate the wettability of the sensor in presence of a humid atmosphere such as that given by exhaled air. Electrochemical tests were carried out in liquid and in aerosol solutions with different concentrations of hydrogen peroxide. The obtained results showed that the current density was proportional to the concentration of hydrogen peroxide, so the sensor can quantify this analyte

Kidney function and symptom development over time in elderly patients with advanced chronic kidney disease:Results of the EQUAL cohort study

Background Initiation of renal replacement therapy often results from a combination of kidney function deterioration and symptoms related to chronic kidney disease (CKD) progression. We investigated the association between kidney function decline and symptom development in patients with advanced CKD. Methods In the European Quality study on treatment in advanced CKD (EQUAL study), a European prospective cohort study, patients with advanced CKD aged ≥65 years and a kidney function that dropped <20 mL/min/1.73 m2 were followed for 1 year. Linear mixed-effects models were used to assess the association between kidney function decline and symptom development. The sum score for symptom number ranged from 0 to 33 and for overall symptom severity from 0 to 165, using the Dialysis Symptom Index. Results At least one kidney function estimate with symptom number or overall symptom severity was available for 1109 and 1019 patients, respectively. The mean (95% confidence interval) annual kidney function decline was 1.70 (1.32; 2.08) mL/min/1.73 m2. The mean overall increase in symptom number and severity was 0.73 (0.28; 1.19) and 2.93 (1.34; 4.52) per year, respectively. A cross-sectional association between the level of kidney function and symptoms was lacking. Furthermore, kidney function at cohort entry was not associated with symptom development. However, each mL/min/1.73 m2 of annual kidney function decline was associated with an extra annual increase of 0.23 (0.07; 0.39) in the number of symptoms and 0.87 (0.35; 1.40) in overall symptom severity. Conclusions A faster kidney function decline was associated with a steeper increase in both symptom number and severity. Considering the modest association, our results seem to suggest that repeated thorough assessment of symptom development during outpatient clinic visits, in addition to the monitoring of kidney function decline, is important for clinical decision-making

Effect of Vitamin D Receptor Activation on the AGE/RAGE System and Myeloperoxidase in Chronic Kidney Disease Patients

Vitamin D receptor (VDR) activation has been reported to increase circulating levels of the advanced glycation end products (AGE) and their decoy receptor (RAGE). However, until now, the effect of VDR activation on AGE and RAGE has not been tested in the setting of a randomized, double-blind clinical trial. We have therefore analyzed the effect of VDR activation by paricalcitol on pentosidine, S100A12/ENRAGE, and RAGE and on established biomarkers of oxidative stress like myeloperoxidase in CKD patients in the PENNY trial. At baseline, human S100A12/ENRAGE, RAGE, and myeloperoxidase, but not pentosidine, were intercorrelated, and the association between S100A12/ENRAGE and myeloperoxidase (r=0.71, P<0.001) was the strongest among these correlations. Paricalcitol failed to modify biomarkers of the AGE/RAGE system and myeloperoxidase in unadjusted and adjusted analyses by the generalized linear model (GLM). No effect modification by other risk factors was registered. Paricalcitol does not modify biomarkers of the AGE/RAGE system and myeloperoxidase in CKD patients. The apparent increase in RAGE levels by VDR activation reported in previous uncontrolled studies is most likely due to confounding factors rather than to VDR activation per se. This trial is registered with NCT01680198

Monitoring Risk Factors and Improving Adherence to Therapy in Patients With Chronic Kidney Disease (Smit-CKD Project): Pilot Observational Study

Background: Chronic kidney disease is a major public health issue, with about 13% of the general adult population and 30% of the elderly affected. Patients in the last stage of this disease have an almost uniquely high risk of death and cardiovascular events, with reduced adherence to therapy representing an additional risk factor for cardiovascular morbidity and mortality. Considering the increased penetration of mobile phones, a mobile app could educate patients to autonomously monitor cardiorenal risk factors. Objective: With this background in mind, we developed an integrated system of a server and app with the aim of improving self-monitoring of cardiovascular and renal risk factors and adherence to therapy. Methods: The software infrastructure for both the Smit-CKD server and Smit-CKD app was developed using standard web-oriented development methodologies preferring open source tools when available. To make the Smit-CKD app suitable for Android and iOS, platforms that allow the development of a multiplatform app starting from a single source code were used. The integrated system was field tested with the help of 22 participants. User satisfaction and adherence to therapy were measured by questionnaires specifically designed for this study; regular use of the app was measured using the daily reports available on the platform. Results: The Smit-CKD app allows the monitoring of cardiorenal risk factors, such as blood pressure, weight, and blood glucose. Collected data are transmitted in real time to the referring general practitioner. In addition, special reminders improve adherence to the medication regimen. Via the Smit-CKD server, general practitioners can monitor the clinical status of their patients and their adherence to therapy. During the test phase, 73% (16/22) of subjects entered all the required data regularly and sent feedback on drug intake. After 6 months of use, the percentage of regular intake of medications rose from 64% (14/22) to 82% (18/22). Analysis of the evaluation questionnaires showed that both the app and server components were well accepted by the users. Conclusions: Our study demonstrated that a simple mobile app, created to self-monitor modifiable cardiorenal risk factors and adherence to therapy, is well tolerated by patients affected by chronic kidney disease. Further studies are required to clarify if the use of this integrated system will have long-term effects on therapy adherence and if self-monitoring of risk factors will improve clinical outcomes in this population