La medicina hospitalaria del siglo XXI. ¿Qué está cambiando?

El objetivo de este artículo es analizar los cambios que se han producido en el ejercicio de la medicina en los últimos años. La irrupción de la tecnología en la actividad diaria ha supuesto grandes modificaciones en nuestra manera de diagnosticar y tratar a los pacientes y es muy probable que este impacto sea mayor en el futuro. Esto ha supuesto grandes ventajas en cuanto a la obtención y manejo de la información de la enorme cantidad de datos clínicos y analíticos que se generan cada día. Por otra parte, la tecnología también ha modificado el quehacer diario de los profesionales sanitarios, con cambios en la dedicación a diferentes tareas y nuevos sistemas organizativos y de realización de trabajo en equipo. No se pretende ir en contra de estos avances tan notables, pero creo necesario este análisis con el fin de situarnos en el contexto actual en el que se ejercen las profesiones sanitarias y por lo tanto poder prever que nos depara el futuro. Finalmente, comentaré las perspectivas que se vislumbran en el horizonte cercano respecto al diagnóstico, cuidados y tratamiento de nuestros enfermos.The aim of this paper is to analyze the changes in medical profession in the last decades. Technology has irrupted in the daily activity and has brought many modifications in the way that doctors diagnose and treat patients, and it is expected that his impact will be even greater in the future. Technology has involved many advantages with respect to the recovery and management of the huge quantity of clinical and analytical data generated in health institutions. Furthermore, technology has changed the daily work of health professionals, with modifications in tasks and new organizational systems and team-based activities. We are not against these important advances, but it is advisable to analyze these changes with the objective of knowing our actual situation and to facilitate the adaptation to these changes in the future. Finally, I will discuss the future perspectives related to diagnosis, care and treatment of our patients

Cyclosporine A-induced apoptosis in renal tubular cells is related to oxidative damage and mitochondrial fission

22 p.Cyclosporine A (CsA) nephrotoxicity has been linked to reactive oxygen species (ROS) production in renal cells. We have demonstrated that the antioxidant Vitamin E (Vit E) abolished renal toxicity in vivo and in vitro models. As one of the main sources of intracellular ROS are mitochondria, we studied the effects of CsA on several mitochondrial functions in LLC-PK1 cells. CsA induced ROS synthesis and decreased reduced glutathione (GSH). The drug decreased mitochondrial membrane potential (m) and induced physiological modifications in both the inner (IMM) and the outer mitochondrial membranes (OMM). In the IMM, CsA provoked mitochondrial permeability tran-sition pores (MPTP) and cytochrome c was liberated into the intermembrane space. CsA also induced pore formation in the OMM, allowing that intermembrane space contents can reach cytosol. Furthermore, CsA altered the mitochondrial dynamics, inducing an increase in mitochondrial fission; CsA increased the expression of dynamin related protein 1 (Drp1) that contributes to mitochondrial fission, and decreased the expression of mitofusin 2 (Mfn2) and optic atrophy protein 1 (Opa1), proteins involved in the fusion process. All these phenomena were related to apoptosis. These effects were inhibited when cells were treated with the antioxidant Vit E suggesting that they were mediated by the synthesis of ROS.Junta de Comunidades de Castilla la ManchaInstituto de Salud Carlos II

La ciclosporina a origina estrés oxidativo y disfunción mitocondrial en células tubulares renales

9 p.Estudiamos el efecto de la ciclosporina A (CsA) sobre la estructura y función mitocondrial en células LLC-PK1. Las células se incubaron durante 24 horas con CsA 1 µM y se analizó la producción de anión superóxido, contenido de NAD(P)H, oxidación de cardiolipina y potencial de membrana mitocondrial; además se estudió la formación de radicales libres y el contenido de glutatión reducido intracelular. Nuestros resultados demuestran que la CsA provocó un aumento del anión superóxido mitocondrial de modo paralelo al descenso de NAD(P)H; además, se produjo oxidación de la cardiolipina de la membrana interna y un descenso del potencial de membrana mitocondrial. Finalmente, observamos un aumento de la producción de radicales libres intracelulares y un descenso del glutatión reducido. En conclusión, la CsA produce modificaciones importantes en la fisiología y estructura mitocondrial con aumento de la síntesis de especies reactivas de oxígeno y descenso de la capacidad antioxidante, hechos que podrían justificar la toxicidad celular de la droga.Junta de Comunidades de Castilla-La Manch

Vitamin E protects against the mitochondrial damage caused by cyclosporin A in LLC-PK1 cells

27 p.Cyclosporin A (CsA) has nephrotoxic effects known to involve reactive oxygen species (ROS), since antioxidants prevent the kidney damage induced by this drug. Given that mitochondria are among the main sources of intracellular ROS, the aims of our study were to examine the mitochondrial effects of CsA in the porcine renal endothelial cell line LLC-PK1 and the influence of the antioxidant Vitamin E (Vit E). Following the treatment of LLC-PK1 cells with CsA, we assessed the mitochondrial synthesis of superoxide anion, permeability transition pore opening, mitochondrial membrane potential, cardiolipin peroxidation, cytochrome c release and cellular apoptosis, using flow cytometry and confocal microscopy procedures. Similar experiments were done after Vit E preincubation of cells. CsA treatment increased superoxide anion in a dose-dependent way. CsA opened the permeability transition pores, caused Bax migration to mitochondria, and decreased mitochondrial membrane potential and cardiolipin content. Also CsA released cytochrome c into cytosol and provoked cellular apoptosis. Vit E pretreatment inhibited the effects that CsA induced on mitochondrial structure and function in LLC-PK1 cells and avoided apoptosis. CsA modifies mitochondrial LLC-PK1 cell physiology with loss of negative electrochemical gradient across the inner mitochondrial membrane and increased lipid peroxidation. These features are related to apoptosis and can explain the cellular damage that CsA induces. As Vit E inhibited these effects, our results suggest that they were mediated by an increase in ROS production by mitochondriaJunta de Comunidades de Castilla-La Manch

Intoxicaciones por setas ¿todavía existen hoy?

Presentamos el caso de una paciente de 55 años vegana, que ingresa por presentar cuadro de nauseas, vómitos y deterioro general secundario a la ingesta de Amanita próxima. La paciente sufrió un síndrome norleucínico con fracaso renal agudo oligoanúrico, que requirió tratamiento con hemodiálisis urgente. La evolución de la paciente fue satisfactoria con recuperación completa de la función renal al cabo de 3 semanas. A propósito de este caso revisamos los efectos tóxicos de las principales setas y su tratamiento.We treated a 55-year old patient with nausea, vomiting and general malaise secondary to the ingestion of Amanita proxima. Our patient suffered from a norleucinic syndrome, with oligoanuric acute kidney failure; she was treated with urgent hemodialysis. The clinical outcome of our patient was satisfactory and complete recovery of kidney function was observed after three weeks. We review of the main toxic effects of mushrooms and their treatment

Factors associating with differences in the incidence of renal replacement therapy among elderly : data from the ERA-EDTA Registry

Background. The incidence of renal replacement therapy (RRT) in the general population >= 75 years of age varies considerably between countries and regions in Europe. Our aim was to study characteristics and survival of elderly RRT patients and to find explanations for differences in RRT incidence. Methods. Patients >= 75 years of age at the onset of RRT in 2010-2013 from 29 national or regional registries providing data to the European Renal Association-European Dialysis and Transplant Association Registry were included. Chi-square and Mann-Whitney U tests were used to assess variation in patient characteristics and linear regression was used to study the association between RRT incidence and various factors. Kaplan-Meier curves and Cox regression were employed for survival analyses. Results. The mean annual incidence of RRT in the age group >= 75 years of age ranged from 157 to 924 per million age-related population. The median age at the start of RRT was higher and comorbidities were less common in areas with higher RRT incidence, but overall the association between patient characteristics and RRT incidence was weak. The unadjusted survival was lower in high-incidence areas due to an older age at onset of RRT, but the adjusted survival was similar [relative risk 1.00 (95% confidence interval, 0.97-1.03)] in patients from low- and high-incidence areas. Conclusions. Variation in the incidence of RRT among the elderly across European countries and regions is remarkable and could not be explained by the available data. However, the survival of patients in low-and high-incidence areas was remarkably similar.Peer reviewe

Predictors of outcome in a Spanish cohort of patients with Fabry disease on enzyme replacement therapy

Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in patients on ERT. Study design: Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24-120). Results: In 69 patients (42 males, 27 females, mean age 44.6±13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242-128mg/g (p=0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR≤60ml/min/1.73m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043) and in males and in females. Lower baseline eGFR was associated with a 3- to 7-fold increase the risk of clinical events in different Cox models. Conclusions: GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes

Markers of endothelial damage in patients with chronic kidney disease on hemodialysis

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.Support for this work was provided by Plan Nacional de IDi Proyectos de Investigación en Salud of Instituto de Salud Carlos III (ISCIII)–Subdirección General de Evaluación, Fondos de desarrollo regional (FEDER; PI11/01536, PI12/01489, PI14/00806, PI15/01785); Junta de Andalucía grants (P010-CTS-6337, P11-CTS-7352); and Fundación Nefrológica. P. Buendía, A. Carmona, and C. Luna-Ruiz are fellows from Consejería de Innovacion, Ciencia y Empresa, Junta de Andalucía