Patología cardiovascular y microvesículas en la enfermedad renal crónica

Resumen de la tesis doctoral: El propósito del trabajo es estudiar la patología cardiovascular (CV) en la enfermedad renal crónica {ERC). La importancia de esta investigación viene dada porque la patología CV es la causa más prevalente y principal de muerte en esta población. Como parámetro novedoso estudiamos la relación con la patología CV de las microvesículas para lo que contamos con la colaboración del departamento de biología de sistemas de la Universidadde Alcalá de Henares (UAH). Se trata pues de una tesis clínica en la que hemos reclutado los pacientes de la consulta externa de endocrinología y pacientes en hemodiálisis (HD) del Hospital Universitario Infanta Leonor (HUIL) de Madrid, pero con el importante apoyo experimental de la UAH. Los pacientes con enfermedad renal crónica (ERC) sufren enfermedades cardiovasculares (ECV) con una incidencia muy superior a la observada en la población general. De hecho, las patologías CV continúan siendo la principal causa de morbilidad y mortalidad entre los enfermos con ERC. Para desarrollar estrategias terapéuticas eficaces que reduzcan la morbi-mortalidadde estos pacientes es un objetivo prioritario caracterizar los elementos de asociación entre daño renal y ECV

Acute effect of citrate bath on postdialysis alkalaemia

AbstractIntroductionThe correction of metabolic acidosis caused by renal failure is achieved by adding bicarbonate during dialysis. In order to avoid the precipitation of calcium carbonate and magnesium carbonate that takes place in the dialysis fluid (DF) when adding bicarbonate, it is necessary to add an acid, usually acetate, which is not free of side effects. Thus, citrate appears as an advantageous alternative to acetate, despite the fact that its acute effects are not accurately known.ObjectiveTo assess the acute effect of a dialysis fluid containing citrate instead of acetate on acid-base balance and calcium-phosphorus metabolism parameters.Material and methodsA prospective crossover study was conducted with twenty-four patients (15 male subjects and 9 female subjects). All patients underwent dialysis with AK-200-Ultra-S monitor with SoftPac® dialysis fluid, made with 3 mmol/L of acetate and SelectBag Citrate®, with 1 mmol/L of citrate and free of acetate. The following were measured before and after dialysis: venous blood gas monitoring, calcium (Ca), ionic calcium (Cai), phosphorus (P) and parathyroid hormone (PTH).ResultsDifferences (p<0.05) were found when using the citrate bath (C) compared to acetate (A) in the postdialysis values of: pH, C: 7.43 (0.04) vs. A: 7.47 (0.05); bicarbonate, C: 24.7 (2.7) vs. A: 27.3 (2.1) mmol/L; base excess (BEecf), C: 0.4 (3.1) vs. A: 3.7 (2.4) mmol/L; corrected calcium (Cac), C: 9.8 (0.8) vs. A: 10.1 (0.7) mg/dL; and Cai, C: 1.16 (0.05) vs. A: 1.27 (0.06) mmol/L. No differences were found in either of the parameters measured before dialysis.ConclusionDialysis with citrate provides better control of postdialysis acid-base balance, decreases/avoids postdialysis alkalaemia, and lowers the increase in Cac and Cai. This finding is of special interest in patients with predisposing factors for arrhythmia and patients with respiratory failure, carbon dioxide retention, calcifications and advanced liver disease

Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification in vitro

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.Instituto de Salud Carlos IIISociedad Española de NefrologíaUniversidad de AlcaláGrupo SantanderUniversity fo California San Dieg

Long-term remission with rituximab in a patient with severe hepatitis C virus-induced mixed cryoglubulinemia

Mixed cryoglobulinemia (MC) is a small-vessel systemic vasculitis characterized by the presence of cryoglobulins, immunoglobulin complexes that precipitate at low temperatures (< 37 ºC) inducing the inflammatory process. The most frequent etiology is hepatitis C infection (HCV) (1). Rituximab (RTX), an anti-CD20 monoclonal antibody, has recently emerged as the treatment of choice for severe MC (2). We present a case of severe hepatitis C virus-induced MC that was controlled and maintained in remission with RTX for 26 months, a remarkable prolonged period of time