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The progression of chronic kidney disease (CKD) involves the development of alterations in mineral metabolism that are closely related to cardiovascular outcomes and bone disease. Hypomagnesemia is associated with more rapid progression of CKD and other comorbidities. Our objective was to analyze in CKD patients stages 3–4 the impact of the administration of magnesium (Mg) carbonate on bone mineral density (BMD) and hemodynamic changes associated with by vascular calcification (VC).

The progression of chronic kidney disease (CKD) involves the development of alterations in mineral metabolism that are closely related to cardiovascular outcomes and bone disease. Hypomagnesemia is associated with more rapid progression of CKD and other comorbidities. Our objective was to analyze in CKD patients stages 3–4 the impact of the administration of magnesium (Mg) carbonate on bone mineral density (BMD) and hemodynamic changes associated with by vascular calcification (VC).

La hemodiafiltración con reinfusión endógena del ultrafiltrado (HFR) es una técnica de diálisis caracterizada por un cartucho de resina con poder adsorbente que combina los mecanismos difusión, convección y adsorción en un solo esquema terapéutico. Después de cerca de 20 años de experiencia clínica con HFR, el presente artículo revisa la evidencia acumulada con esta técnica, planteando si la adición de la adsorción, como tercer mecanismo depurativo, debería ser el siguiente paso en el tratamiento de los pacientes en hemodiálisis. La HFR, a pesar de producir una extensa eliminación de toxinas urémicas, ha demostrado reducir la pérdida de nutrientes y componentes fisiológicos durante la sesión de diálisis frente a la hemodiafiltración on-line, mitigando el estado inflamatorio y el estrés oxidativo en esta población. Además de su facilidad de uso, la técnica también es altamente biocompatible y puede utilizarse en situaciones de un acceso vascular comprometido. En base a estas observaciones, la HFR parece ser una técnica especialmente útil para pacientes con elevada comorbilidad, incluyendo aquellos con fragilidad, desnutrición o enfermedad cardiovascular. En esta revisión, como panel de consenso de nefrólogos con experiencia clínica en HFR, examinamos la literatura existente y resumimos nuestros puntos de vista sobre cómo usar esta técnica, qué perfil de paciente puede ser más adecuado para la HFR, y cómo prescribir y monitorizar de manera práctica esta modalidad de diálisis.

Anemia is a common complication of chronic kidney disease (CKD) and is associated with a decrease in quality of life and an increased risk of transfusions, morbidity and mortality, and progression of CKD. The Anemia Working Group of the Sociedad Española de Nefrología conducted a Delphi study among experts in anemia in CKD to agree on relevant unanswered questions by existing evidence. The RAND/UCLA consensus methodology was used. We defined 15 questions with a PICO structure, followed by a review in scientific literature databases. Statements to each question were developed based on that literature review. Nineteen experts evaluated them using an iterative Two-Round Delphi-like process. Sixteen statements were agreed in response to 8 questions related to iron deficiency and supplementation with Fe (impact and management of iron deficiency with or without anemia, iron deficiency markers, safety of i.v. iron) and 7 related to erythropoiesis stimulating agents (ESAs) and/or hypoxia-inducible factor stabilizers (HIF), reaching consensus on all of them (individualization of the Hb objective, impact and management of resistance to ESA, ESA in the immediate post-transplant period and HIF stabilizers: impact on ferrokinetics, interaction with inflammation and cardiovascular safety). There is a need for clinical studies addressing the effects of correction of iron deficiency independently of anemia and the impact of anemia treatment with various ESA on quality of life, progression of CKD and cardiovascular events.

A selenium-containing metal–organic framework with remarkable antioxidant capacity and ROS-scavenging activity was constructed by a controlled de novoencapsulation approach of a glycoconjugate mimetic, specifically a sp2-iminoglycolipid bearing a selenoureido fragment (DSeU), within a zeolitic-imidazolate framework exoskeleton. Biocompatible and homogeneous nanosized particles of ∼70 nm (DSeU@ZIF8) were obtained, which could be efficiently internalized in cells, overcoming the poor solubility in biological media and limited bioavailability of glycolipids. The ZIF-particle served as nanocarrier for the intracellular delivery of the selenocompound to cells, promoted by the acidic pH inside endosomes/lysosomes. As demonstrated by in vitrostudies, the designed DSeU@ZIF8 nanoparticles displayed a high antioxidant activity at low doses; lower intracellular ROS levels were observed upon the uptake of DSeU@ZIF8 by human endothelial cells. Even more interesting was the finding that these DSeU@ZIF8 particles were able to reverse to a certain level the oxidative stress induced in cells by pre-treatment with an oxidizing agent. This possibility of modulating the oxidative stress in living cells may have important implications in the treatment of diverse pathological complications that are generally accompanied with elevated ROS levels.

Al igual a como ocurrió en el año 2011, cuando la Sociedad Española de Nefrología (SEN) publicó la adaptación española a las guías universales Kidney Disease Initiative Global Outcomes(KDIGO) sobre alteraciones del metabolismo óseo-mineral en la enfermedad renal crónica (CKD-MBD), este documento contiene una actualización y adaptación a nuestro medio de las guías KDIGO del 2017. En este campo, al igual que en muchos otros nefrológicos, no se ha podido contestar irrefutablemente muchas cuestiones pendientes aún. Sin embargo, no hay duda acerca de la estrecha relación entre el complejo CKD-MBD/patología cardiovascular/morbimortalidad, nuevos ensayos clínicos aleatorizados en algunas áreas o la aparición de nuevos fármacos han proporcionado notables avances en este campo y crearon la necesidad de dicha actualización. Así, destacamos las discretas divergencias que ofrecemos en los objetivos ideales de las alteraciones bioquímicas del complejo CKD-MBD respecto a las sugerencias de las KDIGO (en relación, por ejemplo, con la hormona paratiroidea o fosfato), el papel de la vitamina D nativa y análogos en el control del hiperparatiroidismo secundario, así como la contribución de nuevos captores de fosfato y calcimiméticos. Asimismo, es de destacar la adopción de importantes novedades en el diagnóstico de las alteraciones óseas del paciente renal y la necesidad de tomar actitudes más proactivas en su tratamiento. En cualquier caso, la velocidad a la que acaecen novedades actualmente, aunque menor de la que sería deseable, sí impulsan globalmente la necesidad de actualizaciones con menor demora (por ejemplo, a través de Nefrología al día).

En este estudio presentamos los resultados del subgrupo de pacientes españoles del estudio VERIFIE, primer estudio postautorización prospectivo que evalúa la seguridad y efectividad a largo plazo del oxihidróxido sucroférrico (OHS) en pacientes en diálisis con hiperfosfatemia durante la práctica clínica habitual.

El hiperparatiroidismo secundario es uno de los componentes integrales de las alteraciones del metabolismo óseo-mineral en la enfermedad renal crónica (ERC) o complejo chronic kidney disease-mineral bone disorder. Se ha demostrado que en el desarrollo y progresión del hiperparatiroidismo secundario intervienen muchos factores, estrechamente interrelacionados, pero la presencia e importancia de la hiporrespuesta (o resistencia) a la acción de la hormona paratiroidea (PTH) es poco comprendida. En esta revisión analizaremos sus antecedentes, factores que intervienen, así como alguno de los mecanismos moleculares que podrían explicarla. La presencia de resistencia a la acción biológica de la PTH no es única en la ERC, ya que también se presenta para otras hormonas, habiéndose incluso usado el término de «uremia como una enfermedad de receptores». Esta hiporrespuesta a la PTH tiene importantes implicaciones clínicas, dado que no solo permite explicar parte de la patogenia progresiva de la hipersecreción de PTH e hiperplasia paratiroidea, sino también la creciente prevalencia de enfermedad ósea adinámica en la población con ERC. De este modo, subrayamos la importancia de controlar, sin normalizar completamente, los niveles de PTH en los distintos estadios de ERC, dado que un cierto incremento de sus niveles supone inicialmente una adaptación clínica. Futuros estudios a nivel molecular sobre la uremia, o la reciente descripción del efecto directo del fosfato sobre la actividad del receptor sensor de calcio como sensor de fosfato, podrían resultar valiosos incluso más allá de explicar la hiporrespuesta a la PTH en la ERC.

Si tenemos en cuenta que el riñón es el órgano clave para mantener el balance de los diferentes electrolitos corporales y del equilibrio ácido base, podemos suponer la importancia del estatus hidroelectrolítico en el paciente con insuficiencia renal. Para evaluar la situación hidroelectrolítica en los pacientes con insuficiencia renal crónica (IRC) es necesario tener en cuenta 3 puntos clave: balance de sodio, balance de potasio y equilibrio ácido-base.

El diagnóstico de la insuficiencia renal aguda (IRA) en el paciente hospitalizado requiere realizar una historia clínica exhaustiva y una correcta exploración física e interpretación de las pruebas complementarias. Es muy importante realizar una aproximación diagnóstica sindrómica inicial con la mayor exactitud posible, valorando si existe alteración funcional, aproximándonos en la medida de lo posible a los mecanismos fisiopatológicos y, por tanto, a la etiología. La importancia radica en que depende de cuál sea la etiología, ya sea prerrenal, posrenal o parenquimatosa, el tratamiento va a ser diferente, y el pronóstico del cuadro de IRA dependerá de un correcto diagnóstico y tratamiento inicial.

La insuficiencia renal aguda (IRA) puede afectar hasta al 8-10% de los pacientes hospitalizados y se asocia con una elevada tasa de morbimortalidad, tanto a corto como medio/largo plazo. Lo más importante de esta entidad, junto con la detección y tratamiento precoces, es la prevención. Una vez establecida la IRA es necesario buscar las causas y evitar aquellas que pueden producir daño renal. En esta actualización se revisará su tratamiento y se hablará del tratamiento de la IRA mediante el uso de terapia renal sustitutiva (TRS).La sobrecarga de volumen en pacientes con IRA se asocia con un peor pronóstico del cuadro, por lo que se le debe prestar especial atención. Respecto al tratamiento no farmacológico en pacientes con IRA funcional, por hipoperfusión renal, los cristaloides son preferibles a los coloides para la mayoría de los pacientes, y los almidones de hidroxietilo deben ser evitados por el mayor riesgo de provocar IRA que requiera TRS. También se abordará el tratamiento de cuadros de IRA en ancianos, pacientes con insuficiencia cardíaca y pacientes cirróticos.

Las enfermedades renales suponen un conjunto de patologías heterogéneo, cuya base patológica se corresponde con un cuadro sindrómico determinado. Se definen, principalmente, 9 principales síndromes renales, cada uno de ellos o un conjunto de ellos (pueden coexistir) suponen el origen de una serie de enfermedades renales determinadas. Los síndromes renales a los que nos referimos son: hematuria, proteinuria, síndrome nefrótico, síndrome nefrítico, hipertensión arterial, fracaso renal agudo, enfermedad renal crónica, tubulopatías e infecciones urinarias. Para el diagnóstico es importante seguir un orden de estudio, primero realizar una historia clínica detallada (antecedentes personales y familiares y una anamnesis completa); luego una exploración física minuciosa y, por último, las pruebas diagnósticas complementarias que se realizarán de forma escalonada. Es importante un diagnóstico de certeza precoz, ya que las enfermedades renales suelen evolucionar con el tiempo, llegando incluso a requerir técnicas de reemplazo renal, convirtiéndose así en una enfermedad crónica con un elevado coste en morbi/mortalidad y un elevado coste económico. Esto hace imprescindible el conocimiento de los factores de riesgo de progresión renal y las medidas de actuación correspondientes.

El déficit de 25-OH-vitamina D (25-OH-D) es común en los pacientes en hemodiálisis (HD). Por otra parte, es bien conocida la elevada incidencia de hiperparatiroidismo secundario en este grupo de pacientes, y lo importante que es su adecuado control. La 25-OH-D está implicada en la regulación de la homeostasis del calcio, por lo que tener niveles adecuados puede contribuir en el control del metabolismo óseo-mineral.

Patients on haemodialysis (HD) have a high prevalence of 25-OH-vitamin D (25-OH-D)deficiency. Secondary hyperparathyroidismis a common condition in these patients, which is very important to control. 25-OH-D is involved in regulating calcium homeostasis. As such, appropriate levels of this vitamin could help to control bone mineral metabolism.

Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinical and demographic criteria. MVs from plasma and several monocyte subpopulations (CD142+/CD16+, CD14+/CD162+) were analyzed by flow cytometry, and the plasma concentrations of Ang1 and Ang2 were quantified by ELISA. Data on CVD were gathered over the 5.5 yr after these samples were obtained. MV level, monocyte subpopulations (CD14+/CD162+and CD142+/CD16+), and Ang2-to-Ang1 ratios increased in HD patients with DM compared with non-DM patients. Moreover, MV level above the median (264 MVs/µl) was associated independently with greater mortality. MVs, monocyte subpopulations, and Ang2-to-Ang1 ratio can be used as predictors for CVD. In addition, MV level has a potential predictive value in the prevention of CVD in HD patients. These parameters undergo more extensive changes in patients with DM.

Hemodiafiltration with endogenous reinfusion of the ultrafiltrate (HFR) is a dialysis technique characterized by a resin cartridge with adsorptive properties that combines the mechanisms of diffusion, convection, and adsorption in a single therapeutic regimen. After nearly 20 years of clinical experience with HFR, this article reviews the accumulated evidence with this technique, considering whether adsorption reduction, as a third purification mechanism, should be the next step in the treatment of hemodialysis patients. HFR, beyond producing an extensive removal of uremic toxins, has demonstrated to reduce the loss of nutrients and other physiological components during the dialysis session as compared to online hemodiafiltration, ameliorating the inflammatory state and oxidative stress in this population. In addition to its ease of use, the technique is also highly biocompatible and can be used in patients with a compromised vascular access. Based on these observations, HFR appears to be an especially useful therapy for high-comorbidity patients, including those with frailty, malnutrition, or cardiovascular disease. In this review, we, as a consensus panel of nephrologists experienced with HFR, survey existing literature and summarize our views on when to use this technique, which patients may be best suited for HFR, and how to effectively prescribe and monitor this modality of dialysis in daily clinical practice.

As in 2011, when the Spanish Society of Nephrology (SEN) published the Spanish adaptation to the Kidney Disease: Improving Global Outcomes (KDIGO) universal Guideline on Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), this document contains an update and an adaptation of the 2017 KDIGO guidelines to our setting. In this field, as in many other areas of nephrology, it has been impossible to irrefutably answer many questions, which remain pending. However, there is no doubt that the close relationship between the CKD-MBD/cardiovascular disease/morbidity and mortality complex and new randomised clinical trials in some areas and the development of new drugs have yielded significant advances in this field and created the need for this update. We would therefore highlight the slight divergences that we propose in the ideal objectives for biochemical abnormalities in the CKD-MBD complex compared to the KDIGO suggestions (for example, in relation to parathyroid hormone or phosphate), the role of native vitamin D and analogues in the control of secondary hyperparathyroidism and the contribution of new phosphate binders and calcimimetics. Attention should also be drawn to the adoption of important new developments in the diagnosis of bone abnormalities in patients with kidney disease and to the need to be more proactive in treating them. In any event, the current speed at which innovations are taking place, while perhaps slower than we might like, globally drives the need for more frequent updates (for example, through Nefrología al día).

Although phosphorus (P) is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO43-), with tightly regulated plasma levels that are associated with deleterious effects and mortality when these are out of bounds. The growing interest in the accumulation of PO43-in human pathophysiology originated in its attributed role in the pathogenesis of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). In this article, we review the mechanisms by which this effect was justified and we commemorate the important contribution of a Spanish group led by Dr. M. Rodríguez, just 25 years ago, when they first demonstrated the directeffect of PO43-on the regulation of the synthesis and secretion of parathyroid hormone (PTH) by maintaining the structural integrity of the parathyroid glands in their original experimental model. In addition to demonstrating the importance of arachidonic acid (AA) and the phospholipase A2-AA pathway as a mediator of parathyroid gland response, these findings were predecessors of the recent description of the important role of PO43-on the activity of the calcium sensor-receptor, and also fueled various lines of research on the importance of PO43-overload not only for the pathophysiology of SHPT but also in its systemic pathogenic role.

The authors report a model for predicting development of CMV‐specific CD8+ immunity in CMV‐seropositive solid organ transplant candidates and show that assessment of pretransplant CD8+ immune response to CMV is recommended in CMV‐seropositive candidates with a lower probability of developing CMV‐specific CD8+ T cell response, such as non‐renal candidates, those under 50, or those without HLA‐A1 or HLA‐A2 alleles.

This cross-sectional study analyzes factors associated with the development of CMV-specific CD8+ response, measured by IFNg production after cytomegalovirus (CMV) peptide stimulation, in CMV-seropositive solid organ transplantation candidates. A total of 114 candidates were enrolled, of whom 22.8% (26/114) were nonreactive (IFNγ < 0.2 IU/mL). Multivariate logistic regression analysis showed that age, HLA alleles and organ to be transplanted were associated with developing CMV-specific CD8+ immunity (reactive; IFNγ ≥ 0.2 IU/mL). The probability of being reactive was higher in candidates over 50 than in those under 50 (OR 6.33, 95%CI 1.93–20.74). Candidates with HLA-A1 and/or HLA-A2 alleles had a higher probability of being reactive than those with non-HLA-A1/non-HLA-A2 alleles (OR 10.97, 95%CI 3.36–35.83). Renal candidates had a higher probability of being reactive than lung (adjusted OR 8.85, 95%CI 2.24–34.92) and liver candidates (OR 4.87, 95%CI 1.12–21.19). The AUC of this model was 0.84 (p < 0.001). Positive and negative predictive values were 84.8% and 76.9%, respectively. In renal candidates longer dialysis was associated with an increased frequency of reactive individuals (p = 0.040). Therefore, although the assessment of CMV-specific CD8+ response is recommended in all R+ candidates, it is essential in those with a lower probability of being reactive, such as non-renal candidates, candidates under 50 or those with non-HLA-A1/non-HLA-A2 alleles.

Vascular calcification (VC) is a frequent complication of chronic kidney disease (CKD) and is a predictor of cardiovascular morbidity and mortality. In the present study, we investigated the potential involvement of endothelial microparticles (MPs) and endothelial progenitor cells (EPCs) in the generation of VC in CKD patients. The number of circulating EMPs is greater in patients with VC than without VC (307 ± 167 vs. 99 ± 75 EMPs/μl, P< 0.001). The percentage of EPCs is significantly lower in patient with VC than in patients without VC (0.14 ± 0.11% vs. 0.25 ± 0.18%, P= 0.002). The number of EPCs expressing osteocalcin (OCN) was higher in VC patients (349 ± 63 cells/100,000) than in non-VC patients (139 ± 75 cells/100,000, P< 0.01). In vitro, MPs obtained from CKD patients were able to induce OCN expression in EPCs from healthy donors; the increase in OCN expression was more accentuated if MPs were obtained from CKD patients with VC. MPs from CKD patients also induced OCN expression in vascular smooth muscle cells and fibroblasts. In CKD patients, the rise in endothelial MPs associated with a decrease in the number of EPCs, suggesting an imbalance in the processes of endothelial damage and repair in CKD patients, mainly those with VC. Our results suggest that EPCs, through OCN expression, may directly participate in the process of VC.

La anemia es una complicación frecuente de la enfermedad renal crónica (ERC) y se asocia con una disminución en la calidad de vida y a un mayor riesgo de transfusiones, de morbimortalidad y de progresión de la ERC. El Grupo de Trabajo en Anemia de la Sociedad Española de Nefrología realizó un estudio Delphi entre expertos en anemia de la ERC para consensuar respuestas a preguntas relevantes que no se hubieran podido resolver con la evidencia existente. Se empleó la metodología de consensos RAND/UCLA. Se definieron 15 preguntas con una estructura PICO, seguida de una revisión en bases de datos de literatura científica. A partir de la evidencia se formularon enunciados. Diecinueve expertos los evaluaron mediante un proceso iterativo tipo Delphi a dos rondas. Se consensuaron 16 enunciados en respuesta a 8 preguntas referidas a la ferropenia y suplementación con Fe (impacto y gestión de ferropenia con o sin anemia, marcadores de ferropenia, seguridad de hierro i.v.) y a 7 relacionadas con agentes estimuladores de la eritropoyesis (AEE) y/o con estabilizadores del factor inducible por la hipoxia (HIF), alcanzándose consenso en todos ellos (individualización del objetivo de Hb, impacto y gestión de resistencia a AEE, AEE en el periodo inmediato post trasplante y estabilizadores de HIF: impacto sobre la ferrocinética, interacción con inflamación y seguridad cardiovascular). Existe una necesidad de estudios clínicos que aborden los efectos de la corrección del déficit de Fe con independencia de la anemia y el impacto del tratamiento de esta con diversos AEE sobre la calidad de vida, la progresión de ERC y los eventos cardiovasculares.

Aunque el fósforo (P) es un elemento indispensable para la vida, en la naturaleza no se encuentra en estado nativo sino combinado en forma de fosfatos inorgánicos (PO43-), con niveles plasmáticos estrechamente regulados que se asocian a efectos deletéreos y mortalidad cuando estos se encuentran fuera de la normalidad. El interés creciente sobre el acúmulo de PO43-en la fisiopatología humana se originó en el papel que se le atribuyó en la patogenia del hiperparatiroidismo secundario (HPTS) a la enfermedad renal crónica (ERC). En este artículo revisamos los mecanismos por los cuales se justificaba dicho efecto y conmemoramos la importante contribución de un grupo español liderado por el Dr. M. Rodríguez, ahora hace justo 25 años, cuando demostraron por primera vez el efecto directodel PO43-sobre la regulación de la síntesis y secreción de hormona paratiroidea (PTH, manteniendo la integridad estructural de las glándulas paratiroides en su nuevo modelo experimental. Además de demostrar la importancia del ácido araquidónico (AA) y la vía de fosfolipasa A2-AA como mediadora de respuestas en la glándula paratiroidea, estos hallazgos fueron predecesores de la reciente descripción del importante papel del PO43-sobre la actividad del receptor-sensor de calcio y alimentaron asimismo diversas líneas de investigación sobre la importancia de la sobrecarga de PO43-no sólo en la fisiopatología del HPTS sino también en su papel patogénico sistémico.

AbstractBackground: Uremia is associated to host defense mechanism disorders. Lymphocyte apoptosis, which may cause alteration of the immune system, is increased in uremic patients. The aim of the present study was to determine if, in addition to uremia, dialysis membranes with different biocompatibility and permeability have an effect on lymphocyte apoptosis. Methods: Cell apoptosis and Fas expression were assessed using flow cytometry in four groups of patients: (1) uremic non-dialyzed (Non-D) patients; (2) hemodialysis (HD) patients on hemophan; (3) low-flux polysulfone, and (4) high-flux polysulfone membrane. Ten healthy volunteers were used ascontrols. Results: At baseline, lymphocytes from patients on hemophan showed an increase in apoptosis (18.4 ± 6.9%) as compared with Non-D (7.2 ± 2.8%; p &lt; 0.001), low-flux (6.4 ± 2.4%; p &lt; 0.001), high-flux (2.6 ± 1.2%; p &lt; 0.001) and controls (2.0 ± 1.0%; p &lt; 0.001). Fas expression was similar in lymphocytes from Non-D and hemophan dialyzed patients (40.5 ± 5% vs. 40.4 ± 6%), and in both groups it was greater than low-flux (30%±7%; p &lt; 0.001), high-flux (11 ± 4%; p &lt; 0.001) and controls (12.6 ± 3%; p &lt; 0.001). When lymphocytes were cultured for 48 h, apoptosis was similar in Non-D and hemophan (27.0 ± 4.3% vs. 27.1 ± 6.9%); apoptosis of lymphocyte from patients on low-flux (14.1 ± 3.5%) was greater than on high-flux polysulfone membrane (7.0 ± 2.0%; p &lt; 0.001). Conclusion: These findings suggest that in dialysis patients lymphocyte apoptosis is influenced not only by the biocompatibility but also by the permeability of the dialysis membrane.Copyright © 2005 S. Karger AG, Basel

In uraemia there is a reduction in the total number of T lymphocytes and an imbalance in the ratio of Th1/Th2 T-helper (Th) lymphocytes. A higher rate of apoptosis in T lymphocytes has been reported in haemodialysis patients. The aims of the present study were to assess the Th1/Th2 pattern in uraemia and to evaluate whether a relative increase in Th1 apoptosis may explain the Th1/Th2 imbalance observed in uraemic patients.

Background. Mononuclear cells from patients dialysed with cellulosic membranes undergo rapid apoptosis in vitro. The aim of the present study was to determine whether the apoptosis associated with cellulosic haemodialysis membrane shares similar features with the spontaneous apoptosis described in normal monocytes. Thus, we determined whether apoptosis is dependent on caspase‐3 activity and is inhibited by lipopolysaccharide (LPS), which are two features of spontaneous apoptosis in normal monocytes.Methods. We examined mononuclear cells from healthy subjects and from 14 end‐stage renal failure patients on haemodialysis with cellulosic membranes (n=7) and non‐cellulosic membranes (n=7). Isolated mononuclear cells were cultured for 48 h. To determine the effect of haemodialysis membrane exposure on caspase‐3 activity, on mononuclear apoptosis, or both, cells from healthy subjects were cultured in mini‐dialysers with the same membrane types that were used in the haemodialysis patients. Caspase‐3 active form was determined by flow cytometric analysis using anti‐human‐active caspase‐3 antibodies. The effect of LPS and Ac‐DEVD‐CHO, a specific inhibitor of active caspase‐3, was also evaluated. Cell apoptosis was assessed by the terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP nick‐end labelling method.Results. After 48 h of culture, the percentage of mononuclear cells expressing the active form of caspase‐3 was greater in patients dialysed with cellulosic membranes than in patients using non‐cellulosic membranes and in healthy subjects. This increase in caspase‐3 activity was associated with a high rate of apoptosis, which was prevented by Ac‐DEVD‐CHO, an inhibitor of caspase‐3 activity. LPS decreased both apoptosis and caspase‐3 activity in mononuclear cells from patients dialysed with cellulosic membranes. Finally, in cells from healthy subjects, both caspase‐3 activation and apoptosis were induced after incubation with cellulosic membranes. In contrast, the active form of caspase‐3 was not increased in cells cultured with non‐cellulosic membranes and was significantly lower than with cellulosic membranes.Conclusion. These findings suggest that the apoptosis of mononuclear cells induced by cellulosic haemodialysis membranes occurs through a pathway that is similar to the spontaneous apoptosis of normal monocytes. They additionally suggest that LPS regulates the proteolytic activation of caspase‐3.

Mononuclear cells from patients dialysed with cellulosic membranes undergo rapid apoptosis in vitro. The aim of the present study was to determine whether the apoptosis associated with cellulosic haemodialysis membrane shares similar features with the spontaneous apoptosis described in normal monocytes. Thus, we determined whether apoptosis is dependent on caspase-3 activity and is inhibited by lipopolysaccharide (LPS), which are two features of spontaneous apoptosis in normal monocytes.

Introduction. Cardiovascular disease (CVD), as the leading cause of morbidity and mortality in patients on renal replacement therapy (RRT), has a central role in everyday nephrological practice.Methods. Consensus was reached on key points relating to the clinical approach and treatment of the main cardiovascular risk factors in RRT patients (hypertension, anaemia, hyperparathyroidism, dyslipidaemia, new emerging risk factors). In addition, the role of convective treatments on cardiovascular outcomes was examined.Results. Hypertension should be managed by aiming at blood pressure values of 140/90 mmHg (160/90 mmHg in the elderly), firstly by ensuring target dry body weight is achieved. No single class of drug has proved superior to others in RRT patients, provided that the blood pressure target is achieved, although ACE inhibitors have shown specific organ protection in high‐risk patients (HOPE study) and are well tolerated. Anaemia should be managed by using erythropoietin and iron supplements, aiming at haemoglobin levels of 12 g/dl and keeping serum ferritin levels <500 ng/ml. The management of hyperparathyroidism is currently unsatisfactory, as calcium supplements have the potential to increase cardiovascular calcification. While awaiting new calcium‐ and aluminium‐free phosphate binders, it is essential to ensure dialysis adequacy. Clinical studies are in progress to assess the real impact of lipid‐lowering drugs in RRT. In the meantime, serum LDL‐cholesterol <160 mg/dl and triglycerides <500 mg/dl may be desirable targets. The impact of new emerging risk factors (inflammation and chronic infection, hyperhomocysteinaemia, metabolic waste‐product accumulation) and their proper management are still under research. Convective dialysis treatments may confer some degree of protection from dialysis‐related amyloidosis and mortality, but clinical data on this important issue are still controversial and no definitive conclusions can be drawn at present.Conclusion. CVD prevention and treatment is a great challenge for the nephrologist. Achieving evidence‐based consensus can help in encouraging the implementation of best clinical practice in line with the progress of current knowledge.

Cardiovascular disease (CVD), as the leading cause of morbidity and mortality in patients on renal replacement therapy (RRT), has a central role in everyday nephrological practice.