Publications by authors named "Patricia de Sequera"

38 Publications

Iron replacement therapy in the management of anaemia in non-dialysis Chronic kidney disease patients: Perspective of the Spanish Nephrology Society Anaemia Group.

Nefrologia 2021 May 11. Epub 2021 May 11.

Servicio de Nefrología, Hospital Universitario Puerta de Hierro Majadahonda, REDInREN ISCiii 016/009/009 RETYC, Majadahonda, Madrid, Spain.

This work presents an update on the management of iron deficiency in patients with chronic kidney disease (CKD), either with or without anaemia. A review is made of the recommendations of the guidelines for the treatment of iron deficiency in CKD. It also presents new studies on iron deficiency in patients with CKD, as well as new findings about iron therapy and its impact on clinical outcomes. Anaemia is a common complication of CRF, and is associated with a decrease in the quality of life of the patients, as well as an increase in morbidity and mortality. Iron deficiency (absolute or functional) is common in non-dialysis chronic kidney disease patients, and may cause anaemia or a low response to erythropoiesis-stimulating agents. For this reason, the clinical guidelines for the treatment of the anaemia in Nephrology indicate the correction of the deficiency in the presence of anaemia. Iron replacement therapy is indicated in patients with CKD and anaemia (Hb < 12 g/dl) in accordance with the guidelines. There is no unanimity in the indication of iron replacement therapy in patients with Hb > 12 g/dl, regardless of whether they have an absolute or functional iron deficiency. Intravenous iron replacement therapy is safe, more efficient and rapid than oral therapy for achieving an increase haemoglobin lels and reducing the dose of erythropoiesis-stimulating agents. For the administration of intravenous iron in non-dialysis chronic renal failure patients a strategy of high doses and low frequency would be preferred on being more convenient for the patient, preserves better the venous capital, and is safe and cost-effective. Iron plays an essential role in energy metabolism and other body functions beyond the synthesis of haemoglobin, for which the iron deficiency, even in the absence of anaemia, could have harmful effects in patients with CKD. The correction of the iron deficiency, in the absence of anaemia is associated with functional improvement in patients with heart failure, and in muscle function or fatigue in patients without CKD. Despite the evidence of benefits in the correction of iron deficiency in patients with CKD, more studies are required to evaluate the impact of the correction of the iron deficiency in the absence of anaemia on morbidity and mortality, quality of life and physical capacity, as well as the long-term effect of oral and intravenous iron replacement therapy in this population.
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http://dx.doi.org/10.1016/j.nefroe.2020.11.011DOI Listing
May 2021

A high magnesium concentration in citrate dialysate prevents oxidative stress and damage in human monocytes .

Clin Kidney J 2021 May 30;14(5):1403-1411. Epub 2020 Aug 30.

Dpto de Biología de Sistemas, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.

Background: The use of dialysis fluids (DFs) during haemodialysis has been associated with increased oxidative stress and reduced serum magnesium (Mg) levels, contributing to chronic inflammation. Since the role of Mg in modulating immune function and reducing oxidative stress has been demonstrated, the aim of this study was to characterize whether increasing the Mg concentration in DFs could protect immune cells from oxidative stress and damage.

Methods: The effect of citrate [citrate dialysis fluid (CDF), 1 mM] or acetate [acetate dialysis fluid (ADF), 3 mM] dialysates with low (0.5 mM; routinely used) or high (1 mM, 1.25 mM and 2 mM) Mg concentrations was assessed in THP-1 human monocytes. The levels of reactive oxygen species (ROS), malondialdehyde (MDA) and oxidized/reduced (GSSG/GSH) glutathione were quantified under basal and inflammatory conditions (stimulation with lipopolysaccharide, LPS).

Results: The increase of Mg in CDF resulted in a significant reduction of ROS production under basal and inflammatory conditions (extremely marked in 2 mM Mg; P 0.001). These effects were not observed in ADF. Interestingly, in a dose-dependent manner, high Mg doses in CDF reduced oxidative stress in monocytes under both basal and inflammatory conditions. In fact, 2 mM Mg significantly decreased the levels of GSH, GSSG and MDA and the GSSG/GSH ratio in relation to 0.5 mM Mg.

Conclusions: CDF produces lower oxidative stress than ADF. The increase of Mg content in DFs, especially in CDF, could have a positive and protective effect in reducing oxidative stress and damage in immune cells, especially under inflammatory conditions.
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http://dx.doi.org/10.1093/ckj/sfaa131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087128PMC
May 2021

Developing the subspecialty of cardio-nephrology: The time has come. A position paper from the coordinating committee from the Working Group for Cardiorenal Medicine of the Spanish Society of Nephrology.

Nefrologia (Engl Ed) 2021 Apr 20. Epub 2021 Apr 20.

Nephrology Department, Hospital Universitario Infanta Leonor, University Complutense of Madrid, Madrid, Spain.

Patients with the dual burden of chronic kidney disease (CKD) and cardiovascular disease (CVD) experience unacceptably high rates of morbidity and mortality, which also entail unfavorable effects on healthcare systems. Currently, concerted efforts to identify, prevent and treat CVD in CKD patients are lacking at the institutional level, with emphasis still being placed on individual specialty views on this topic. The authors of this position paper endorse the need for a dedicated interdisciplinary team of subspecialists in cardio-nephrology that manages appropriate clinical interventions across the inpatient and outpatient settings. There is a critical need for training programs, guidelines and best clinical practice models, and research funding from nephrology, cardiology and other professional societies, to support the development of the subspecialty of cardio-nephrology. This position paper from the coordinating committee from the Working Group for Cardiorenal Medicine of the Spanish Society of Nephrology (S.E.N.) is intended to be the starting point to develop the subspecialty of cardio-nephrology within the S.E.N.. The implementation of the subspecialty in day-to-day nephrological practice will help to diagnose, treat, and prevent CVD in CKD patients in a precise, clinically effective, and health cost-favorable manner.
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http://dx.doi.org/10.1016/j.nefro.2021.02.003DOI Listing
April 2021

Suboptimal personal protective equipment and SARS-CoV-2 infection in Nephrologists: a Spanish national survey.

Clin Kidney J 2021 Apr 18;14(4):1216-1221. Epub 2021 Jan 18.

Nephrology Department, Hospital Universitario Infanta Leonor, Madrid, Spain.

Background: Healthcare workers have been overexposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the current pandemic, but there is little information on the impact of SARS-CoV-2 on nephrologists. The aim of this study was to assess SARS-CoV-2 infections in nephrologists in the first and second pandemic waves, describing risk factors and clinical features.

Methods: This national survey was sent to Spanish nephrologists. Epidemiological data, comorbidities and medications were collected and compared between infected and non-infected nephrologists. Symptoms, prescribed treatments and outcomes are described for infected nephrologists.

Results: Three hundred and twenty-seven nephrologists (66% female, age 46 ± 11 years) completed the survey. Of them, 62 (19%) were infected by SARS-CoV-2. Infection was detected by real-time reverse transcription-polymerase chain reaction in the 37 symptomatic patients (62%) and by serological tests in 25 (38%) asymptomatic individuals. Five (8%) of the infected nephrologists were hospitalized. Contrary to the general population, most infections occurred during the first pandemic wave and, specifically, during the first month, when personal protective equipment (PPE) shortages were more severe. Factors associated with infection in univariate analysis were younger age (P = 0.004), work in non-nephrology departments (P = 0.045), higher exposure to coronavirus disease 2019 patients (P < 0.001), lack of appropriate PPE (P < 0.001) and non-O ABO blood group. In an adjusted multivariate model, only lack of appropriate PPE remained predictive of infection [hazard ratio 3.5 (95% confidence interval 1.9-6.8), P < 0.0001].

Conclusions: SARS-CoV-2 infection was frequent among nephrologists, was frequently diagnosed late and was associated with working conditions.
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http://dx.doi.org/10.1093/ckj/sfab009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928998PMC
April 2021

Nomenclature in nephrology: preserving 'renal' and 'nephro' in the glossary of kidney health and disease.

J Nephrol 2021 06 13;34(3):639-648. Epub 2021 Mar 13.

Guy's & Saint Thomas' Hospital, London, UK.

A recently published nomenclature by a "Kidney Disease Improving Global Outcomes" (KDIGO) Consensus Conference suggested that the word "kidney" should be used in medical writings instead of "renal" or "nephro" when referring to kidney disease and kidney health. Whereas the decade-old move to use "kidney" more frequently should be supported when communicating with the public-at-large, such as the World Kidney Day, or in English speaking countries in communications with patients, care-partners, and non-medical persons, our point of view is that "renal" or "nephro" should not be removed from scientific and technical writings. Instead, the terms can coexist and be used in their relevant contexts. Cardiologists use "heart" and "cardio" as appropriate such as "heart failure" and "cardiac care units" and have not replaced "cardiovascular" with "heartvessel", for instance. Likewise, in nephrology, we consider that "chronic kidney disease" and "continuous renal replacement therapy" should coexist. We suggest that in scientific writings and technical communications, the words "renal" and "nephro" and their derivatives are more appropriate and should be freely used without any pressure by medical journals to compel patients, care-partners, healthcare providers, researchers and other stakeholders to change their selected words and terminologies. We call to embrace the terms "kidney", "renal" and "nephro" as they are used in different contexts and ask that scientific and medical journals not impose terminology restrictions for kidney disease and kidney health. The choice should be at the discretion of the authors, in the different contexts including in scientific journals.
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http://dx.doi.org/10.1007/s40620-021-01011-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192439PMC
June 2021

Effective glutamate clearance from the systemic circulation by hemodialysis: Potential relevance for cerebral ischemia management.

Artif Organs 2021 Feb 9. Epub 2021 Feb 9.

Servicio de Nefrología, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Spain.

High glutamate levels after head trauma or cerebral ischemia have neurotoxic effects. The objective of the present study was to evaluate the efficacy of hemodialysis to remove glutamate from the blood and to assess the behavior of this small molecule. Ten patients with end-renal disease on hemodialysis were included in the study. Glutamate clearance was evaluated within the first hour of hemodialysis on a midweek dialysis day on five patients who underwent low flux hemodialysis, whereas the other five patients underwent highly efficient hemodialysis (high flux hemodialysis on one day and online hemodiafiltration on another day). Glutamate clearance with hemodialysis was very effective and did not show any differences between the techniques (low flux: 214 [55], high flux: 204 [37], online hemodiafiltration: 202 [16], median (interquartile range), P = .7). Glutamate clearance was almost equivalent to vascular access plasma flow and it was not affected by dialyzer permeability or ultrafiltration rate. After a hemodialysis session, a significant decrease in glutamate blood level was observed (prehemodialysis: 59.7 [36.1], posthemodialysis 37.0 [49.2], P = .005). Dialysis performed under fasting condition showed higher glutamate reduction rate (60%) than that under feeding condition (20%). Hemodialysis may be an effective method to reduce glutamate blood levels, and the molecule clearance does not differ between the different techniques used. Considering previous results in experimental models, hemodialysis without hemodynamic stress, could be considered for reducing glutamate neurotoxic effects in acute ischemic strokes of patients in chronic hemodialysis programs.
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http://dx.doi.org/10.1111/aor.13933DOI Listing
February 2021

Iron replacement therapy in the management of anaemia in non-dialysis chronic renal failure patients: Perspective of the Spanish Nephrology Society Anaemia Group.

Nefrologia (Engl Ed) 2021 Mar-Apr;41(2):123-136. Epub 2021 Jan 28.

Servicio de Nefrología, Hospital Universitario Puerta de Hierro Majadahonda, REDInREN ISCiii 016/009/009 RETYC, Majadahonda, Madrid, España.

This work presents an update on the management of iron deficiency in patients with chronic renal failure (CRF), either with or without anaemia. A review is made of the recommendations of the guidelines for the treatment of iron deficiency in CRF. It also presents new studies on iron deficiency in patients with CRF, as well as new findings about iron deficiency and its impact on clinical outcomes. Anaemia is a common complication of CRF, and is associated with a decrease in the quality of life of the patients, as well as an increase in morbidity and mortality. Iron deficiency (absolute or functional) is common in non-dialysis chronic renal failure patients, and may cause anaemia or a low response to erythropoiesis-stimulating agents. For this reason, the clinical guidelines for the treatment of the anaemia in Nephrology advise the correction of the deficiency in the presence of anaemia. Iron replacement therapy is indicated in patients with CRF and anaemia (Hb < 12 g/dL) in accordance with the guidelines. There is no unanimity in the indication of iron replacement therapy in patients with Hb>12 g/dL, regardless of whether they have an absolute or functional iron deficiency. Intravenous iron replacement therapy is safe, more efficient and rapid than oral therapy for achieving an increase haemoglobin levels and reducing the dose of erythropoiesis-stimulating agents. For the administration of intravenous iron in non-dialysis chronic renal failure patients a strategy of high doses and low frequency would be preferred on being more convenient for the patient, better conserving of the venous tree, and on being safe and cost-effective. Iron plays an essential role in energy metabolism and other body functions beyond the synthesis of haemoglobin synthesis, for which the iron deficiency, even in the absence of anaemia, could have a harmful effect in patients with CRF. The correction of the iron deficiency, in the absence of anaemia is associated with functional improvement in patients with heart failure, and in muscle function or fatigue in patients without CRF. Despite the evidence of benefits in the correction of iron deficiency in patients with CRF, more studies are required to evaluate the impact of the correction of the iron deficiency in the absence of anaemia on morbidity and mortality, quality of life and physical capacity, as well as the long-term effect of oral and intravenous iron replacement therapy in this population.
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http://dx.doi.org/10.1016/j.nefro.2020.11.003DOI Listing
January 2021

Position statement of the Spanish Society of Nephrology on the SARS-CoV-2 vaccines.

Nefrologia (Engl Ed) 2021 Jan 1. Epub 2021 Jan 1.

Servicio de Nefrología, Hospital Universitario Infanta Leonor, Madrid, España; Junta Directiva de la Sociedad Española de Nefrología.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide over the last year causing more than one million deaths. Several treatments have tried to modify the natural history of the coronavirus disease 2019 (COVID-19) but only corticosteroids have demonstrated to be effective in moderate or severe affectation. In that situation, the development of vaccines for preventing the SARS-CoV-2 infection has focused the attention of the scientific community. At present, available messenger RNA-based technology vaccines have received the approval of local and international sanitary authorities. In this position statement, the Spanish Society of Nephrology wants to state that patients with chronic kidney disease and healthcare workers are at high-risk for contagion and complications of COVID-19 so they must have priority in the vaccine administration.
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http://dx.doi.org/10.1016/j.nefro.2020.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775792PMC
January 2021

Hypomagnesaemia in haemodialysis is associated with increased mortality risk: its relationship with dialysis fluid.

Nefrologia (Engl Ed) 2020 Sep - Oct;40(5):552-562. Epub 2020 Jul 7.

Servicio de Nefrología, Hospital Universitario Infanta Leonor, Madrid, España.

Hypomagnesaemia in haemodialysis (HD) is associated with increased mortality risk: its relationship with dialysis fluid (DF).

Introduction: Low concentrations of magnesium (Mg) in blood have been linked to the development of diabetes, hypertension, arrhythmias, vascular calcifications and an increased risk of death in the general population and in haemodialysis patients. The composition of the dialysis fluid in terms of its magnesium concentration is one of the main determinants of magnesium in haemodialysis patients.

Objective: To study magnesium concentrations in haemodialysis patients, their predictive mortality rate and what factors are associated with hypomagnesaemia and mortality in haemodialysis.

Methods: Retrospective study of a cohort of prevalent haemodialysis patients followed up for two years. Serum magnesium was measured every six months. The analysis used the initial and average magnesium values for each patient, comparing patients with magnesium below the mean (2.1mg/dl) with those with magnesium above the mean. During the follow-up, three types of dialysis fluid were used: type 1, magnesium 0.5 mmol/l; type 3, magnesium 0.37 mmol/l (both with acetate); and type 2, magnesium 0.5 mmol/l with citrate.

Results: We included 137 haemodialysis patients in the study, of which 72 were male and 65 were female, with a mean age of 67 (15) [26-95] years old. Of this group, 57 patients were diabetic, 70 were on online haemodiafiltration (OL-HDF) and 67 were on high-flow haemodialysis (HF-HD). The mean magnesium of the 93 patients with dialysis fluid type 1 was 2.18 (0.37) mg/dl. In the 27 patients with dialysis fluid type 3 it was 2.02 (0.42) mg/dl. And in the 17 with dialysis fluid type 2 it was 1.84 (0.24) mg/dl (p=.01). There was a pronounced direct relationship between Mg and P and albumin. After a mean follow-up of 16.6 (8.9) [3-24] months, 77 remained active, 24 had died and 36 had been transplanted or transferred. Patients with magnesium above than 2.1mg/dl had a longer survival (p=.008). The survival of patients with the three types of dialysis fluid did not differ significantly (Log-Rank, p=.424). Corrected for blood magnesium, patients with dialysis fluid with citrate have better survival (p=.009). The COX regression analysis shows how age, serum albumin, magnesium, dialysis technique and type of dialysis fluid have an independent predictive mortality rate.

Conclusions: Low serum magnesium levels have a greater association with an increased risk of mortality compared to high levels. The type of dialysis fluid affects the magnesium concentration and the risk of death.
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http://dx.doi.org/10.1016/j.nefro.2020.04.013DOI Listing
July 2020

Haemodialysis patients have worse postural balance with an associated risk of falls.

Nefrologia (Engl Ed) 2020 Nov - Dec;40(6):655-663. Epub 2020 Jul 7.

Facultad de Enfermería, Fisioterapia y Podología, Universidad Complutenese de Madrid, Madrid, España.

Introduction: Postural balance is the result of a complex interaction of sensory input which keeps us upright. Haemodialysis patients have alterations which can lead to postural instability and a risk of falls. Our objective was to analyse postural stability and its relationship with the risk of falls in haemodialysis patients using a force platform.

Material And Methods: This was a prospective cross-sectional study. Postural balance was recorded using a force platform in prevalent haemodialysis patients. We collected epidemiological, dialysis, analytical and treatment data. The incidence of falls was recorded over the 6 months following the tests. The postural stability analysis was performed with a portable strain gauge platform (AMTI AccuGait®) and a specific software unit for stabilometry (Balance Trainer® program). We measured 31 balance parameters; the balance variables used were: Area95; AreaEffect; VyMax; Xrange and Yrange. The stabilometry studies were performed in 3 situations: with eyes open; with eyes closed; and with the patient performing a simultaneous task. We performed one study at the start of the dialysis session, and a second study at the end. Stabilometry was measured in a control group under similar conditions.

Results: We studied 32 patients with a mean age of 68 years old; of this group, 20 subjects were male and 12 were female. Their mean weight was 74kg, with a mean BMI of 27.6kg/m. In the controls, there were no significant differences in the stabilometry between the 3 situations studied. Both pre- and post-haemodialysis, patients with closed eyes showed greater imbalance, and there were significant differences with the other situations and controls. We found a significant increase in instability after the haemodialysis session, and greater instability in the 13 patients with diabetes (P<.05). The 4 patients with hyponatraemia (Na<136mmol/l) had worse balance in the simultaneous task situation (P=.038). Various drugs, such as insulin (P=.022), antiplatelet agents (P=.036) and beta-blockers (P=.029), were associated with imbalance. The 10 patients who suffered falls had greater imbalance, Yrange, Xrange, Area95 and AreaEffect, both pre- and post-haemodialysis (P<.05) than those without falls.

Conclusions: Haemodialysis patients have alterations which can lead to postural instability and a risk of falls. Prevention programmes which include specific exercises to improve balance could be beneficial in reducing the risk of falls in this population.
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http://dx.doi.org/10.1016/j.nefro.2020.04.014DOI Listing
July 2020

[High prevalence of asymptomatic COVID-19 in haemodialysis: learning day by day in the first month of the COVID-19 pandemic].

Nefrologia (Engl Ed) 2020 May - Jun;40(3):279-286. Epub 2020 Apr 30.

Servicio de Nefrología, Hospital Universitario Infanta Leonor, Madrid, España.

Dialysis patients are a risk group for SARS-CoV-2 infection and possibly further complications, but we have little information. The aim of this paper is to describe the experience of the first month of the SARS-CoV-2 pandemic in a hospital haemodialysis (HD) unit serving the district of Madrid with the second highest incidence of COVID-19 (almost 1,000 patients in 100,000h). In the form of a diary, we present the actions undertaken, the incidence of COVID-19 in patients and health staff, some clinical characteristics and the results of screening all the patients in the unit. We started with 90 patients on HD: 37 (41.1%) had COVID-19, of whom 17 (45.9%) were diagnosed through symptoms detected in triage or during the session, and 15 (40.5%) through subsequent screening of those who, until that time, had not undergone SARS-CoV-2 PCR testing. Fever was the most frequent symptom, 50% had lymphopenia and 18.4% <95% O saturation. Sixteen (43.2%) patients required hospital admission and 6 (16.2%) died. We found a cluster of infection per shift and also among those using public transport. In terms of staff, of the 44 people involved, 15 (34%) had compatible symptoms, 4 (9%) were confirmed as SARS-CoV-2 PCR cases by occupational health, 9 (20%) required some period of sick leave, temporary disability to work (ILT), and 5 were considered likely cases. CONCLUSIONS: We detected a high prevalence of COVID-19 with a high percentage detected by screening; hence the need for proactive diagnosis to stop the pandemic. Most cases are managed as outpatients, however severe symptoms are also appearing and mortality to date is 16.2%. In terms of staff, 20% have required sick leave in relation to COVID-19.
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http://dx.doi.org/10.1016/j.nefro.2020.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190471PMC
July 2020

Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification .

Comput Struct Biotechnol J 2020 9;18:953-966. Epub 2020 Apr 9.

Departamento de Biología de Sistemas, Universidad de Alcalá (IRYCIS), Alcalá de Henares, Madrid, Spain.

Vascular calcification (VC), an unpredictable pathophysiological process and critical event in patients with cardiovascular diseases (CVDs), is the leading cause of morbi-mortality and disability in chronic kidney disease (CKD) patients worldwide. Currently, no diagnostic method is available for identifying patients at risk of VC development; the pathology is detected when the process is irreversible. Extracellular vesicles (EVs) from endothelial cells might promote VC. Therefore, their evaluation and characterization could be useful for designing new diagnostic tools. The aim of the present study is to investigate whether microvesicles (MVs) from endothelial cells damaged by uremic toxin and indoxyl sulfate (IS) could induce calcification in human vascular smooth muscle cells (VMSCs). Besides, we have also analyzed the molecular mechanisms by which these endothelial MVs can promote VC development. Endothelial damage has been evaluated according to the percentage of senescence in endothelial cells, differential microRNAs in endothelial cells, and the amount of MVs released per cell. To identify the role of MVs in VC, VSMCs were treated with MVs from IS-treated endothelial cells. Calcium, inflammatory gene expression, and procalcification mediator levels in VSMCs were determined. IS-treated endothelial cells underwent senescence and exhibited modulated microRNA expression and an increase in the release of MVs. VSMCs exposed to these MVs modulated the expression of pro-inflammatory genes and some mediators involved in calcification progression. MVs produced by IS-treated endothelial cells promoted calcification in VSMCs.
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http://dx.doi.org/10.1016/j.csbj.2020.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184105PMC
April 2020

Increasing the Magnesium Concentration in Various Dialysate Solutions Differentially Modulates Oxidative Stress in a Human Monocyte Cell Line.

Antioxidants (Basel) 2020 Apr 15;9(4). Epub 2020 Apr 15.

Departamento de Biología de Sistemas, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.

Oxidative stress is exacerbated in hemodialysis patients by several factors, including the uremic environment and the use of dialysis fluids (DFs) Since magnesium (Mg) plays a key role in modulating immune function and in reducing oxidative stress, we aimed to evaluate whether increasing the Mg concentration in different DFs could protect against oxidative stress in immunocompetent cells in vitro. Effect of ADF (acetate 3 mM), CDF (citrate 1 mM), and ACDF (citrate 0.8 mM + acetate 0.3 mM) dialysates with Mg at standard (0.5 mM) or higher (1, 1.25, and 2 mM) concentrations were assessed in THP-1 monocyte cultures. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels were quantified under basal and uremic conditions (indoxyl sulfate (IS) treatment). Under uremic conditions, the three DFs with 0.5 mM Mg promoted higher ROS production and lipid damage than the control solution. However, CDF and ACDF induced lower levels of ROS and MDA, compared to that induced by ADF. High Mg concentration (1.25 and/or 2 mM) in CDF and ACDF protected against oxidative stress, indicated by reduced ROS and MDA levels compared to respective DFs with standard concentration of Mg. Increasing Mg concentrations in ADF promoted high ROS production and MDA content. Thus, an increase in Mg content in DFs has differential effects on the oxidative stress in IS-treated THP-1 cells depending on the dialysate used.
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http://dx.doi.org/10.3390/antiox9040319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222382PMC
April 2020

Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence.

Front Cell Dev Biol 2020 20;8:185. Epub 2020 Mar 20.

Departamento Biología de Sistemas, Facultad de Medicina y Ciencias de la Salud (IRYCIS), Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.

Cardiovascular diseases (CVDs), especially those involving a systemic inflammatory process such as atherosclerosis, remain the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). CKD is a systemic condition affecting approximately 10% of the general population. The prevalence of CKD has increased over the past decades because of the aging of the population worldwide. Indeed, CVDs in patients with CKD constitute a premature form of CVD observed in the general population. Multiple studies indicate that patients with renal disease undergo accelerated aging, which precipitates the appearance of pathologies, including CVDs, usually associated with advanced age. In this review, we discuss several aspects that characterize CKD-associated CVDs, such as etiopathogenic elements that CKD patients share with the general population, changes in the cellular balance of reactive oxygen species (ROS), and the associated process of cellular senescence. Uremia-associated aging is linked with numerous changes at the cellular and molecular level. These changes are similar to those observed in the normal process of physiologic aging. We also discuss new perspectives in the study of CKD-associated CVDs and epigenetic alterations in intercellular signaling, mediated by microRNAs and/or extracellular vesicles (EVs), which promote vascular damage and subsequent development of CVD. Understanding the processes and factors involved in accelerated senescence and other abnormal intercellular signaling will identify new therapeutic targets and lead to improved methods of diagnosis and monitoring for patients with CKD-associated CVDs.
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http://dx.doi.org/10.3389/fcell.2020.00185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099607PMC
March 2020

Statins and antiplatelet agents are associated with changes in the circulatory markers of endothelial dysfunction in chronic kidney disease.

Nefrologia (Engl Ed) 2019 May - Jun;39(3):287-293. Epub 2019 Feb 4.

Servicio de Nefrología, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, España; REDInREN ISCiii 016/0091009 RETYC, Madrid, España.

Backgrounds And Purposes: Patients with chronic kidney disease (CKD) have higher risk of developing cardiovascular disease. In CKD patients the mechanisms involved in, endothelial damage and the role of different drugs used on these patients are not completely understood. The aim of this work is to analyze the effect of statins and platelet antiaggregant (PA) on endothelial microvesicles (EMVs) and other markers of endothelial dysfunction.

Experimental Approach: Cross-sectional study of 41 patients with CKD 3b-4 and 8 healthy volunteers. Circulating levels of EMVs, vascular endothelial growth factor (VEGF), and advance oxidized protein products (AOPPS) were quantified and the correlation with different comorbidity variables and therapeutic strategies were evaluated.

Results: EMVs are increased in CKD patients as compared with controls (171.1 vs. 68.3/μl, P<.001). It was observed a negative correlation between age and EMVs. Statins and PA were associated with a reduction in EMVs and VEGF levels, independently of the serum total cholesterol levels (TC). The levels of AOPPS and VEGF were not different in CKD vs. controls.

Conclusion: CKD is associated with a change in EMVs, VEGF and AOPP levels. The treatment with statins and PA normalizes these values to almost the observed in controls and this effect is independently of the prevailing TC level. These findings explain the existence of the pleiotropic effects of statins and PA which deserve further studies.
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http://dx.doi.org/10.1016/j.nefro.2018.11.001DOI Listing
May 2020

Mineral and bone disorder management in hemodialysis patients: comparing PTH control practices in Japan with Europe and North America: the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BMC Nephrol 2018 10 5;19(1):253. Epub 2018 Oct 5.

Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.

Background: High-circulating level of parathyroid hormone (PTH) is associated with elevated mortality in dialysis patients. The Japanese Society for Dialysis Therapy guideline suggests a lower PTH target than other international guidelines; thus, PTH control may differ in Japan compared with other regions, and be associated with mortality.

Methods: We analyzed data from hemodialysis patients with ≥3 measurements of PTH during the first 9 months after enrollment in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4-5 (2009-2015). PTH control was assessed by the mean, slope, and mean squared error (MSE) of all PTH measurements over the 9-month run-in period. Distribution of each PTH control was assessed by regions (Europe/Australia/New Zealand [Eur/ANZ], Japan and North America) and dialysis vintage. Mortality rates were compared across PTH control categories using Cox regression models.

Results: Mean PTH was lower in Japan than in other regions across dialysis vintage categories. In patients with dialysis vintage < 90 days, PTH level was more likely to decline > 5% per month in Japan (48% of patients) versus Eur/ANZ (35%) and North America (35%). In patients with dialysis vintage > 1 year, Japanese patients maintained steady PTH, while patients in Eur/ANZ and North America were more likely to experience a PTH increase. Mean PTH was associated with mortality in the overall samples (highest mortality rate for PTH > 600 pg/mL, hazard ratio, 1.35; 95% confidence interval, 1.20 to 1.52 vs PTH 200-399 pg/mL), and the association was obvious in the prevalent patients (hazard ratio, 1.44; 95% confidence interval, 1.26 to 1.65). PTH slope and MSE did not show significant association with mortality in the overall sample as well as in subjects stratified both by region and dialysis vintage.

Conclusion: PTH control in hemodialysis patients, as measured by keeping a stable PTH level over 9 months, was observed in Japan contrasted with other regions. High PTH mean, but not increased PTH slope and MSE, was associated with mortality especially in prevalent patients.
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http://dx.doi.org/10.1186/s12882-018-1056-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173912PMC
October 2018

Unlike Kt, high Kt/V is associated with greater mortality: The importance of low V.

Nefrologia (Engl Ed) 2019 Jan - Feb;39(1):58-66. Epub 2018 Jul 31.

Servicio de Nefrología, Hospital Universitario Infanta Leonor, Madrid, España.

Introduction: Kt/V has been used as a synonym for haemodialysis dose. Patient survival improved with a Kt/V>1; this target was subsequently increased to 1.2 and 1.3. The HEMO study revealed no significant relationship between Kt/V and mortality. The relationship between Kt/V and mortality often shows a J-shaped curve. Is V the confounding factor in this relationship? The objective of this study is to determine the relationship between mortality and Kt/V, Kt and body water content (V) and lean mass (bioimpedance).

Methods: We studied a cohort of 127 prevalent haemodialysis patients, who we followed-up for an average of 36 months. Kt was determined by ionic dialysance, and V and nutrition parameters by bioimpedance. Kt/V, Kt corrected for body surface area (Kt/BSA) and target Kt/BSA were calculated. The mean data from 18,998 sessions were used as haemodialysis parameters, with a mean of 155 sessions per patient.

Results: Mean age was 70.4±15.3 years and 61% were male; 76 were dialysed via an arteriovenous fistula and 65 were on online haemodiafiltration. Weight was 70.6 (16.8)kg; BSA 1.8 (0.25) m; total body water (V) 32.2 (7.41) l and lean mass index (LMI) 11.1 (2.7)kg/m. Mean Kt/V was 1.84 (0.44); Kt 56.1 (7)l and Kt/BSA 52.8 (10.4)l. The mean target Kt/BSA was 49.7 (4.5)l. Mean Kt/BSA-target Kt/BSA +6.4 (7.0)l. Patients with a higher Kt/V had worse survival rates than others; with Kt this is not the case. Higher Kt/V values are due to a lower V, with poorer nutrition parameters. LMI and serum albumin were the parameters that best independently predicted the risk of death and are lower in patients with a higher Kt/V and lower V.

Conclusion: Kt/V is not useful for determining dialysis doses in patients with low or reduced body water. Kt or the Kt/BSA are proposed as an alternative.
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http://dx.doi.org/10.1016/j.nefro.2018.04.006DOI Listing
January 2020

A case report of cyanotic nephropathy.

Nefrologia (Engl Ed) 2019 Jan - Feb;39(1):96-98. Epub 2018 Jun 28.

Servicio de Nefrología, Hospital Universitario Infanta Leonor, Madrid, España.

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http://dx.doi.org/10.1016/j.nefro.2018.05.001DOI Listing
January 2020

Aspirin for Primary Prevention of Cardiovascular Disease and Renal Disease Progression in Chronic Kidney Disease Patients: a Multicenter Randomized Clinical Trial (AASER Study).

Cardiovasc Drugs Ther 2018 06;32(3):255-263

Nephrology Department, Hospital General Universitario Gregorio Marañón, C/ Dr Esquerdo 46, 28007, Madrid, Spain.

Background: Patients with chronic kidney disease (CKD) are at high risk for developing cardiovascular events. However, limited evidence is available regarding the use of aspirin in CKD patients to decrease cardiovascular risk and to slow renal disease progression.

Study Design: Prospective, multicenter, open-label randomized controlled trial.

Setting And Participants: One hundred eleven patients with estimated glomerular filtration rate (eGFR) 15-60 ml/min/1.73 m without previous cardiovascular events.

Intervention: Aspirin treatment (100 mg/day) (n = 50) or usual therapy (n = 61). Mean follow-up time was 64.8 ± 16.4 months.

Outcomes: The primary endpoint was composed of cardiovascular death, acute coronary syndrome (nonfatal MI, coronary revascularization, or unstable angina pectoris), cerebrovascular disease, heart failure, or nonfatal peripheral arterial disease. Secondary endpoints were fatal and nonfatal coronary events, renal events (defined as doubling of serum creatinine, ≥ 50% decrease in eGFR, or renal replacement therapy), and bleeding episodes.

Results: During follow-up, 17 and 5 participants suffered from a primary endpoint in the control and aspirin groups, respectively. Aspirin did not significantly reduce primary composite endpoint (HR, 0.396 (0.146-1.076), p = 0.069. Eight patients suffered from a fatal or nonfatal coronary event in the control group compared to no patients in the aspirin group. Aspirin significantly reduced the risk of coronary events (log-rank, 5.997; p = 0.014). Seventeen patients in the control group reached the renal outcome in comparison with 3 patients in the aspirin group. Aspirin treatment decreased renal disease progression in a model adjusted for age, baseline kidney function, and diabetes mellitus (HR, 0.272; 95% CI, 0.077-0.955; p = 0.043) but did not when adjusted for albuminuria. No differences were found in minor bleeding episodes between groups and no major bleeding was registered.

Limitations: Small sample size and open-label trial.

Conclusions: Long-term treatment with low-dose aspirin did not reduce the composite primary endpoint; however, there were reductions in secondary endpoints with fewer coronary events and renal outcomes. ClinicalTrials.gov Identifier: NCT01709994.
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http://dx.doi.org/10.1007/s10557-018-6802-1DOI Listing
June 2018

Asymmetric cellulose triacetate is a safe and effective alternative for online haemodiafiltration.

Nefrologia (Engl Ed) 2018 May - Jun;38(3):315-320. Epub 2018 Feb 15.

Laboratorio de Fisiología, Universidad de Alcalá, Alcalá de Henares, Madrid, España.

Background: In post-dilution haemodiafiltration only synthetic membranes have been used to date. Asymmetric cellulose triacetate (ATA™) is now available, whose characteristics are suitable for this technique.

Objectives: To describe the in vivo performance and behaviour of this membrane, to identify its depurative effectiveness, use in clinical practice and its biocompatibility, both acute and after one month of treatment.

Methods: Observational prospective study of 23 patients who were dialysed for 4 weeks using an ATA™ membrane and who maintained their prior regimen.

Results: A total of 287 sessions were performed and 264 complete sessions were collected. With an effective time of 243.7 (17.6) min and a mean blood flow of 371.7 (23) ml/min, an average Kt of 56.3 (5.3) l was observed, as well as a convection volume of 27.1 (4.2) l, a filtration fraction of 29.9 (3.7) %, a urea reduction ratio (RR) of 81 (5.2) %, a creatinine RR of 74.7 (4.6) %, a β-microglobulin RR of 76.5 (4.8) % and a retinol binding protein RR of 18.6 (7.6) %. There were no technical problems or alarms. Changing the heparin dosage was not necessary. No increases in C3a or C5a concentrations or leukopenia were observed in the first 30min of the session. Neither the monocyte subpopulations nor IL-β1 or IL-6 were significantly altered after one month of treatment.

Conclusions: The new ATA™ membrane achieves adequate Kt and convection volume, without technical problems and with good biocompatibility and inflammatory profiles. It is therefore a valid option for post-dilution haemodiafiltration, particularly in patients allergic to synthetic membranes.
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http://dx.doi.org/10.1016/j.nefro.2017.11.015DOI Listing
April 2019

Low dose aspirin increases 15-epi-lipoxin A4 levels in diabetic chronic kidney disease patients.

Prostaglandins Leukot Essent Fatty Acids 2017 Oct 24;125:8-13. Epub 2017 Aug 24.

Servicio de Nefrología, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Spanish Kidney Research Network (REDINREN), Madrid, Spain.

Background: Resolution of inflammation is regulated by endogenous lipid mediators, such as lipoxins and their epimers, including 15-epi-lipoxin A4 (15-epi-LXA4). However, there is no information on 15-epi-LXA4 and its in vivo regulation in chronic kidney disease (CKD) patients.

Study Design: Open label randomized clinical trial.

Setting And Participants: 50 participants with chronic kidney disease (CKD) stage 3 and 4 without prior cardiovascular disease (25 in the aspirin group and 25 in the standard group) followed for 46 months.

Intervention: Aspirin (100mg/day) or standard treatment.

Aim: To analyze the effect of aspirin on plasma 15-epi-LXA4 levels and inflammatory markers in CKD patients.

Results: Baseline plasma15-epi-LXA4 levels were lower in diabetic (1.22 ± 0.99ng/ml) than in non-diabetic CKD patients (2.05 ± 1.06ng/ml, p < 0.001) and inversely correlated with glycosylated hemoglobin levels (r = -0.303, p = 0.006). In multivariate analysis, diabetes was associated with lower 15-epi-LXA4 levels, adjusted for age, inflammatory markers and renal function (p = 0.005). In the whole study population, 15-epi-LXA4 levels tended to increase, but not significantly (p = 0.45), after twelve months on aspirin (from mean ± SD 1.84 ± 1.06 to 2.04 ± 0.75ng/ml) and decreased in the standard care group (1.60 ± 1.15 to 1.52 ± 0.68ng/ml, p = 0.04). The aspirin effect on 15-epi-LXA4 levels was more striking in diabetic patients, increasing from 0.94 ± 0.70 to 1.93 ± 0.74ng/ml, p = 0.017.

Conclusions: Diabetic patients with CKD have lower circulating 15-epi-LXA4 levels than non-diabetic CKD patients. Low dose aspirin for 12 months increased 15-epi-LXA4 levels in diabetic patients. Given its anti-inflammatory properties, this increase in 15-epi-LXA4 levels may contribute to the beneficial effects of low dose aspirin.
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http://dx.doi.org/10.1016/j.plefa.2017.08.009DOI Listing
October 2017

Residual Renal Function in Hemodialysis and Inflammation.

Ther Apher Dial 2017 Dec 3;21(6):592-598. Epub 2017 Oct 3.

Biología Sistemas, Universidad de Alcalá de Henares, Alcalá de Henares, Madrid, Spain.

Residual renal function (RRF) has an important effect on uremic toxin clearance, on volume control, on quality of life, and on mortality. In patients with chronic kidney disease (CKD), microinflammation with an increased percentage of CD14 /CD16 inflammatory monocytes has been reported, even with no clinical evidence of inflammation. No correlation has been established between these and RRF in hemodialysis (HD) patients. Our objective was to assess the relationship between RRF and the inflammatory parameters in HD patients. Cross-sectional observational study was carried out on 69 adult patients on chronic HD for at least 6 months, from which demographic, analytic and HD-technique data were collected and the following were measured: (i) RRF with average urea and creatinine clearance ((CCr + CU)/2) in 24-h urine (if >1 mL/min and diuresis >100 mL/day, RRF was considered); (ii) Inflammation through biochemical parameters (C-reactive protein, β microglobulin, albumin) and monocyte subpopulations in peripheral blood. The average age was 70.9 [40-88] years old; 38 (55.1%) were male; and 25 (36.2%) were diabetic. 43.5% (30/69) presented RRF, with an average of ((CCr + CU)/2): 1.8 (2.6) mL/min and diuresis: 454.5 (569) mL /24 h. Patients with RRF presented lower concentrations of C-reactive protein (6.2 vs 21.4 mg/L) (P = 0.038) and a lower percentage of non-classical CD14 /CD16 monocytes (14.6 vs. 28.3%, P = 0.02). In our study, patients with RRF present lower concentrations of inflammatory parameters, which is another reason why its preservation is an essential objective in HD.
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http://dx.doi.org/10.1111/1744-9987.12576DOI Listing
December 2017

Universal Sustained Viral Response to the Combination of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with/without Ribavirin in Patients on Hemodialysis Infected with Hepatitis C Virus Genotypes 1 and 4.

Am J Nephrol 2017 7;45(3):267-272. Epub 2017 Jan 7.

Service of Nephrology, Hospital Universitario Gregorio Marañón, Madrid, Spain.

Background: Hepatitis C virus (HCV) infection is highly prevalent among patients on hemodialysis (HD) and is associated with poor prognosis. Treatment with interferon and ribavirin is poorly tolerated, and few data are available on the impact of new direct-acting antivirals (DAAs). This study was intended to analyze the efficacy and safety of treatment with a combination of ombitasvir/paritaprevir/ritonavir and dasabuvir with/without ribavirin in HCV-infected patients on HD from 3 hospitals.

Methods: This is a multicentric study. We analyze the clinical course of all patients on HD with HCV infection who had been treated with the combination of ombitasvir/paritaprevir/ritonavir and dasabuvir in 3 hospitals in Madrid, Spain. All patients under treatment had undergone Transient elastography (FibroScan®) and HCV RNA (PCR) and HCV genotype were determined simultaneously.

Results: Thirty-five patients aged 53.3 ± 8.9 years (68.6% males) and with genotypes 1 and 4 were treated with the DAA regimen, and 17 were also given ribavirin. The most common etiology was glomerular disease. Sustained viral response was achieved in 100% of patients. Adverse effects were negligible, and no patient had to discontinue treatment. The most significant side effect was anemia, which led to a significant increase in the dose of erythropoiesis-stimulating agents. Anemia was more marked in patients receiving ribavirin. No patients required transfusions.

Conclusion: A combination of ombitasvir/paritaprevir/ritonavir and dasabuvir with/without ribavirin for the treatment of HCV in patients on HD is highly effective and causes minimal side effects. This regimen represents a major advance in disease management. A considerable improvement in prognosis seems likely.
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http://dx.doi.org/10.1159/000454819DOI Listing
December 2017

Lanthanum carbonate oral powder: satisfaction, preference and adherence in French and Spanish patients with end-stage renal disease.

Drugs Context 2016 14;5:212300. Epub 2016 Oct 14.

Kantar Health, Epsom, Surrey, UK; RTI Health Solutions, Barcelona, Spain.

Background: Phosphate binders, such as lanthanum carbonate, control elevated serum-phosphate levels in patients with end-stage renal disease (ESRD). Lanthanum carbonate is available in oral powder and tablet form. The aim of this survey was to investigate satisfaction with, preference for, and adherence to lanthanum carbonate oral powder in patients with ESRD.

Scope: Patients from France and Spain who had been taking lanthanum carbonate powder for at least 4 weeks, and who had experience of other phosphate binders of any formulation, were asked to complete an online or telephone survey. Treatment satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication-9; preference was measured using 5-point Likert scale agreement ratings; and adherence was measured using the Morisky Medication Adherence Scale-4. Data were evaluated using bivariate analyses.

Findings: Overall, 160 patients participated (80 per country). Lanthanum carbonate powder was reported to have a higher effectiveness rating (<0.05), be more convenient (<0.05), and provide a higher level of satisfaction (<0.01) than previous binders. There was an overall preference for lanthanum carbonate powder over previous binders of any formulation (<0.001). Adherence to medication was similar for all binders analysed: 66.3% of French patients adhered to lanthanum carbonate powder, and 65.0% adhered to previous binder treatment (=not significant); 52.5% of Spanish patients adhered to lanthanum carbonate powder, and 56.3% adhered to previous binder treatment (=not significant).

Limitations: The survey enrolled patients who had already experienced phosphate binders before the study began. Information on patient preferences for and adherence to previous phosphate binders was therefore based on the patients' memories of these experiences, which may have been subject to change over time. Although most participants completed the online survey in this study, a telephone survey was used for individuals who could not access the online version; if only one method of data recording had been used, there may have been reduced variation in responses.

Conclusion: Patients with ESRD report increased satisfaction with and preference for lanthanum carbonate powder over other formulations, suggesting that lanthanum carbonate powder is more convenient and easier to use than other formulations.
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http://dx.doi.org/10.7573/dic.212300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081242PMC
October 2016

Follow a recipe to prescribe phosphate during hemodialysis.

Nefrologia 2017 Jan - Feb;37(1):34-38. Epub 2016 Jul 25.

Servicio de Nefrología, Hospital Universitario Infanta Leonor, Madrid, España.

The addition of phosphorus (P) to the dialysate (LD) in the form of enema Casen® is common practice in patients with hypophosphatemia. The estimation of the amount to be used and the identification of the problems that may can occur are not well defined. As a result of our work we propose a practical approach of how to proceed to increase phosphate concentration in the hemodialysate. We present a reasoned formula to calculate how much enema has to be added and the problems that may arise.
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http://dx.doi.org/10.1016/j.nefro.2016.04.005DOI Listing
April 2018

Functional Dependence and Mortality in the International Dialysis Outcomes and Practice Patterns Study (DOPPS).

Am J Kidney Dis 2016 Feb 21;67(2):283-92. Epub 2015 Nov 21.

Arbor Research Collaborative for Health, Ann Arbor, MI; Vanderbilt University Medical Center, Nashville, TN. Electronic address:

Background: Patients receiving long-term dialysis have among the highest mortality and hospitalization rates. In the nonrenal literature, functional dependence is recognized as a contributor to subsequent disability, recurrent hospitalization, and increased mortality. A higher burden of functional dependence with progressive worsening of kidney function has been observed in several studies, suggesting that functional dependence may contribute to both morbidity and mortality in dialysis patients.

Study Design: Prospective cohort study.

Setting & Participants: 7,226 hemodialysis patients from 12 countries in the DOPPS (Dialysis Outcomes and Practice Patterns Study) phase 4 (2009-2011) with self-reported data for functional status.

Predictor: Patients' ability to perform 13 basic and instrumental activities of daily living was summarized to create an overall functional status score (range, 1.25 [most dependent] to 13 [functionally independent]).

Outcome: Cox regression was used to estimate the association between functional status and all-cause mortality, adjusting for several demographic and clinical risk factors for mortality. Median follow-up was 17.2 months.

Results: The proportion of patients who could perform each activity of daily living task without assistance ranged from 97% (eating) to 47% (doing housework). 36% of patients could perform all 13 tasks without assistance (functional status = 13), and 14% of patients had high functional dependence (functional status < 8). Functionally independent patients were younger and had many indicators of better health status, including higher quality of life. Compared with functionally independent patients, the adjusted HR for mortality was 2.37 (95% CI, 1.92-2.94) for patients with functional status < 8.

Limitations: Possible nonresponse bias and residual confounding.

Conclusions: We found a high burden of functional dependence across all age groups and across all DOPPS countries. When adjusting for several known mortality risk factors, including age, access type, cachexia, and multimorbidity, functional dependence was a strong consistent predictor of mortality.
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http://dx.doi.org/10.1053/j.ajkd.2015.09.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530761PMC
February 2016

Is it useful to increase dialysate flow rate to improve the delivered Kt?

BMC Nephrol 2015 Feb 14;16:20. Epub 2015 Feb 14.

Servicio de Nefrologia, Hospital Universitario Infanta Leonor, Gran Vía del Este, No 80, 28031, Madrid, Spain.

Background: Increasing dialysate flow rates (Qd) from 500 to 800 ml/min has been recommended to increase dialysis efficiency. A few publications show that increasing Qd no longer led to an increase in mass transfer area coefficient (KoA) or Kt/V measurement. Our objectives were: 1) Studying the effect in Kt of using a Qd of 400, 500, 700 ml/min and autoflow (AF) with different modern dialysers. 2) Comparing the effect on Kt of water consumption vs. dialysis time to obtain an individual objective of Kt (Ktobj) adjusted to body surface.

Methods: This is a prospective single-centre study with crossover design. Thirty-one patients were studied and six sessions with each Qd were performed. HD parameters were acquired directly from the monitor display: effective blood flow rate (Qbe), Qd, effective dialysis time (Te) and measured by conductivity monitoring, final Kt.

Results: We studied a total of 637 sessions: 178 with 500 ml/min, 173 with 700 ml/min, 160 with AF and 126 with 400 ml/min. Kt rose a 4% comparing 400 with 500 ml/min, and 3% comparing 500 with 700 ml/min. Ktobj was reached in 82.4, 88.2, 88.2 and 94.1% of patients with 400, AF, 500 and 700 ml/min, respectively. We did not find statistical differences between dialysers. The difference between programmed time and Te was 8' when Qd was 400 and 500 ml/min and 8.8' with Qd = 700 ml/min. Calculating an average time loss of eight minutes/session, we can say that a patient loses 24' weekly, 312' monthly and 62.4 hours yearly. Identical Kt could be obtained with Qd of 400 and 500 ml/min, increasing dialysis time 9.1' and saving 20% of dialysate.

Conclusions: Our data suggest that increasing Qd over 400 ml/min for these dialysers offers a limited benefit. Increasing time is a better alternative with demonstrated benefits to the patient and also less water consumption.
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http://dx.doi.org/10.1186/s12882-015-0013-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369100PMC
February 2015

Evaluation of a polynephron dialysis membrane considering new aspects of biocompatibility.

Int J Artif Organs 2015 Jan 23;38(1):45-53. Epub 2015 Jan 23.

2 Research Unit, Foundation for Biomedical Research, Príncipe de Asturias Hospital, Alcalá de Henares, Madrid - Spain.

Purpose: The biocompatibility of dialyzers may influence the inflammatory state of hemodialysis patients. This study compares the effect of a high-flux polynephron membrane with other high-flux membranes, helixone and polyamide, on some inflammation biomarkers based on the analysis of circulating mononuclear cells (MC).

Methods: The study included 47 patients on hemodialysis with helixone and polyamide; 9 formed the control group, without changes in their dialyzers throughout the study, and 38 formed the intervention group, in which their dialyzers were replaced by polynephron. In both groups, blood samples were taken at the beginning of the study before and after hemodialysis session, and at the end of the study 4 months later. In each extraction, biochemical parameters were determined, and MC isolated using Ficoll gradient. Production of reactive oxygen species and the percentage of activated MC (CD14+CD16+) were measured by flow cytometry, and protein levels of heat-shock proteins (Hsp70/Hsp90) studied by Western blot.

Results: After 1 hemodialysis session with different membranes, no significant differences were observed in the different parameters considered. After 4 months of dialysis with polynephron, a significant reduction in the percentage of CD14+CD16+ and in the β2-microglobulin reduction ratio were found, with respect to helixone and polyamide, without changes in the other parameters analyzed.

Conclusions: The use of polynephron for 4 months reduces the percentage of CD14+CD16+ compared to helixone and polyamide, suggesting a better profile regarding activation of the inflammatory response. These findings could be explained by a better biocompatibility or an increased reduction of medium-sized toxic molecules.
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http://dx.doi.org/10.5301/ijao.5000380DOI Listing
January 2015

Psychosocial factors and adherence to drug treatment in patients on chronic haemodialysis.

Nefrologia 2014 Nov;34(6):737-42

Background: The daily pill burden in hemodialysis patients is one of the highest reported to date in any chronic disease. The adherence to prescribed treatment has implications on the quality of life, the survival of patients, and the economic cost of their treatment, this being a priority public health issue.

Objective: To evaluate the adherence to pharmacological treatment examining, among the possible causes of non-adherence, psychosocial factors such as depression, anxiety, cognitive impairment and social support.

Method: Transversal-observational study of thirty five patients that suffer from chronic renal disease and who are on manteinance hemodialysis, evaluated by self-reported measures.

Results: Non-adherent patients have significant higher depression index than adherent patients. Anxiety, cognitive impairment and social support do not show a significant relation with the degree of adherence or compliance with farmacological treatment.

Conclusions: These results suggest that psychological intervention in chronic haemodialysis patients with a severe depression index could increase the degree of fulfillment and general well-being of renal patients.
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http://dx.doi.org/10.3265/Nefrologia.pre2014.Jul.12477DOI Listing
November 2014