Conducting Action Research to Improve Operational Efficiency in Manufacturing: The Case of a First-Tier Automotive Supplier.

Optimising available resources and minimising production costs and throughput time is vital for first-tier suppliers in the worldwide automotive sector. To develop this type of optimisation and efficiency, MAHLE applied Action Research (AR) in one of its factories located in Spain. A multidisciplinary collaborative work team was created with the aim of deploying the AR initiative in combination with Lean Manufacturing and Six Sigma tools. Four improvement and learning cycles were deployed and key performance metrics were defined to collect and measure data in order to analyse the improvements achieved. The application of the AR initiative in the production line of a power filter device enabled improvements in both production times and quality indicators in the manufacturing process. The most outstanding results were the improvements made in the decrease in initial throughput time (34.78%) and in average daily rejections (73.53%). In addition, the AR initiative generated practical and theoretical contributions for business and academia, allowing the AR initiative to be applied in other areas of the company, and contributing to the current state of the art in the industrial application of this methodology.

Comparación del tiempo de cicatrización entre N-butil cianoacrilato y ácido poliglicólico en caninos sometidos a esterilización / Comparison of healing times between N-butyl cyanoacrylate and polyglycolic acid in canines subjected to sterilization

RESUMEN El objetivo de este estudio fue comparar el tiempo de cicatrización entre N-butil cianocrilato (NBC) y ácido poliglicólico (AC) sobre el cierre tisular en caninos sometidos a operaciones de esterilización. Se realizó un estudio observacional, comparativo y descriptivo sobre una población de 80 perros (Canis familiaris) vivos. Los animales se dividieron en cuatro grupos de 20 perros cada uno según sexo y material de sutura, así: primero grupo, hembras que recibieron NBC; segundo grupo, machos y NBC; tercero grupo, hembras y AC como medio de sutura en piel y cuarto grupo, machos y AC. La técnica quirúrgica en hembras fue oforosalpingohisterectomia y en machos orquiectomia. El tiempo de cierre fue estadísticamente (p < 0,05) menor en los grupos de machos y hembras con el adhesivo NBC comparado con los dos grupos tratados con AC. Se concluye que el NBC es un material seguro y eficaz como medio de fijación tisular en ambas técnicas quirúrgicas que disminuye los días de cierre y recuperación.

ABSTRACT The aim of this study was to compare N-butyl cyanoacrylate (NBC) and polyglycolic acid (AC) in tissue closure in canines subjected to sterilization operations. An observational, comparative and descriptive study was conducted in a population of 80 living dogs (Canis familiaris). The animals were divided into 4 groups of 20 dogs each, according to gender and suture material: the first group consisted of females that received NBC; the second group consisted of males that received NBC; the third group consisted of females that received AC as skin suture; and the fourth group was formed by males that received AC. The surgical technique in females was salpingo-oophorectomy, and in males it was orchiectomy. The closure time was statistically (p < 0.05) lower in the male and female groups with the NBC adhesive in comparison to the two groups treated with AC. It was concluded that NBC is a safe and effective material for tissue fixation in both surgical techniques, decreasing times of closure and recovery.

BET Proteins: An Approach to Future Therapies in Transplantation.

In order to develop new efficient therapies for organ transplantation, it is essential to acquire a comprehensive knowledge of the molecular mechanisms and processes, such as immune activation, chronic inflammation, and fibrosis, which lead to rejection and long-term graft loss. Recent efforts have shed some light on the epigenetic regulation associated with these processes. In this context, the bromo and extraterminal (BET) family of bromodomain proteins (BRD2, BRD3, BRD4, and BRDT) have emerged as major epigenetic players, connecting chromatin structure with gene expression changes. These proteins recognize acetylated lysines in histones and master transcription factors to recruit regulatory complex and, finally, modify the transcriptional program. Recent studies indicate that BET proteins are essential in the NF-kB-mediated inflammatory response, during the activation and differentiation of Th17-immune cells, and in profibrotic processes. Here, we review this new body of data and highlight the efficiency of BET inhibitors in several models of diseases. The promising results obtained from these preclinical models indicate that it may be time to translate these outcomes to the transplantation field, where epigenetics will be of increasing value in the coming years.

Albumin-induced apoptosis of tubular cells is modulated by BASP1.

Albuminuria promotes tubular injury and cell death, and is associated with faster progression of chronic kidney disease (CKD) to end-stage renal disease. However, the molecular mechanisms regulating tubular cell death in response to albuminuria are not fully understood. Brain abundant signal protein 1 (BASP1) was recently shown to mediate glucose-induced apoptosis in tubular cells. We have studied the role of BASP1 in albumin-induced tubular cell death. BASP1 expression was studied in experimental puromycin aminonucleoside-induced nephrotic syndrome in rats and in human nephrotic syndrome. The role of BASP1 in albumin-induced apoptosis was studied in cultured human HK2 proximal tubular epithelial cells. Puromycin aminonucleoside induced proteinuria and increased total kidney BASP1 mRNA and protein expression. Immunohistochemistry localized the increased BASP1 to tubular cells. BASP1 expression colocalized with deoxynucleotidyl-transferase-mediated dUTP nick-end labeling staining for apoptotic cells. Increased tubular BASP1 expression was observed in human proteinuric nephropathy by immunohistochemistry, providing evidence for potential clinical relevance. In cultured tubular cells, albumin induced apoptosis and increased BASP1 mRNA and protein expression at 6-48 h. Confocal microscopy localized the increased BASP1 expression in albumin-treated cells mainly to the perinuclear area. A peripheral location near the cell membrane was more conspicuous in albumin-treated apoptotic cells, where it colocalized with actin. Inhibition of BASP1 expression by a BASP1 siRNA protected from albumin-induced apoptosis. In conclusion, albumin-induced apoptosis in tubular cells is BASP1-dependent. This information may be used to design novel therapeutic approaches to slow CKD progression based on protection of tubular cells from the adverse consequences of albuminuria.

Tyrphostins as potential therapeutic agents for acute kidney injury.

Acute kidney injury (AKI) is a syndrome characterized by an acute renal cell injury that leads to sudden loss of renal function. There are currently no clinically validated treatments for AKI besides substituting renal function by dialysis. However, new biomarkers will allow an earlier diagnosis, thus providing a window of opportunity for therapeutic intervention. Tyrphostins are a family of compounds originally designed as protein tyrosine kinase inhibitors. However, some molecules of this family have additional actions, such as inhibition of guanylate and adenylate cyclases, mitochondrial uncoupling or antioxidant effects. We review the potential role of tyrphostins in the prophylaxis and treatment of acute kidney injury on the basis of published studies on animals, in vitro experiments and piecemeal information from humans. The AG 490 and AG 126 tyrphostins have recently been shown to protect from AKI in experimental animal models of ischemia-reperfusion and sepsis-induced injury. AG 490 protects from cyclosporin-induced AKI and AG 1714 protects from cisplatin nephrotoxicity. AG 490 is nephroprotective by inhibiting oxidative stress-related Janus activated kinase-2 (JAK2) activation. Potential applications of AG490 or derivative molecules include AKI of nephrotoxic or ischemic nature, or a combination of both, as may occur in the immediate postransplant period. The molecular targets of AG 126 and AG 1714 are less well characterized. In conclusions, different tyrphostins are nephroprotective in animal models of AKI. The characterization of the molecular targets involved will allow the design of novel therapies that may reach the clinical trial stage.

[Connective tissue growth factor (CTGF): a key factor in the onset and progression of kidney damage]. / El factor de crecimiento de tejido conectivo (CTGF): factor clave en el inicio y la progresión del daño renal.

Connective tissue growth factor (CTGF) is increased in several pathologies associated with fibrosis, including multiple renal diseases. CTGF is involved in biological processes such as cell cycle regulation, migration, adhesion and angiogenesis. Its expression is regulated by various factors involved in renal damage, such as transforming growth factor- , Angiotensin II, high concentrations of glucose and cellular stress. CTGF is involved in the initiation and progression of renal damage to be able to induce an inflammatory response and promote fibrosis, identified as a potential therapeutic target in the treatment of kidney diseases. In this paper we review the main actions of CTGF in renal disease, the intracellular action mechanisms and therapeutic strategies for its blocking.

El factor de crecimiento de tejido conectivo (CTGF): factor clave en el inicio y la progresión del daño renal / No disponible

El factor de crecimiento de tejido conectivo (CTGF) aparece aumentado en diferentes patologías asociadas a fibrosis, incluidas múltiples enfermedades renales. CTGF participa en procesos biológicos, como la regulación del ciclo celular, migración, adhesión y angiogénesis. Su expresión está regulada por diversos factores implicados en el daño renal, entre los que destacan el factor la angiotensina II, el factor de crecimiento transformante-beta, altas concentraciones de glucosa y situaciones de estres celular. CTGF participa en el inicio y progresión del daño renal al ser capaz de inducir una respuesta inflamatoria y promover la fibrosis, señalándole como una posible diana terapéutica en el tratamiento de patologías renales. En este trabajo revisamos las principales acciones de CTGF en la patología renal, los mecanismos intracelulares de actuación y las estrategias terapéuticas para su bloqueo (AU)

Connective tissue growth factor (CTGF) is increased in several pathologies associated with fibrosis, including multiple renal diseases. CTGF is involved in biological processes such as cell cycle regulation, migration, adhesion and angiogenesis. Its expression is regulated by various factors involved in renal damage, such as Angiotensin II, transforming growth factor-beta, high concentrations of glucose and cellular stress. CTGF is involved in the initiation and progression of renal damage to be able to induce an inflammatory response and promote fibrosis, identified as a potential therapeutic target in the treatment of kidney diseases. In this paper we review the main actions of CTGF in renal disease, the intracellular action mechanisms and therapeutic strategies for its blocking (AU)

[Transcriptomics illustrate a deadly TRAIL to diabetic nephropathy]. / La transcriptómica ilustra nuevas vías letales en la nefropatía diabética.

Diabetic nephropathy is the most common cause of endstage renal disease. Approaches targeting angiotensin II significantly delay its progression. However, many patients still need renal replacement therapy. High throughput techniques such as unbiased gene expression profiling and proteomics may identify new therapeutic targets. Cell death is thought to contribute to progressive renal cell depletion in chronic nephropathies. A European collaborative effort recently applied renal biopsy transcriptomics to identify novel mediators of renal cell death in diabetic nephropathy. Twenty-five percent of cell death regulatory genes were upor downregulated in diabetic kidneys. TNF-related apoptosisinducing ligand (TRAIL) and osteoprotegerin had the highest level of expression. In diabetic nephropathy, tubular cells and podocytes express TRAIL. Inflammatory cytokines, including MIF via CD74, upregulate TRAIL. A high glucose environment sensitized renal cells to the lethal effect of TRAIL, while osteoprotegerin is protective. These results suggest that, in addition to glucose levels, inflammation and TRAIL are therapeutic targets in diabetic nephropathy.

La transcriptómica ilustra nuevas vías letales en la nefropatía diabética / No disponible

La nefropatía diabética es la causa más común de enfermedad renal crónica terminal. La modulación terapéutica de la angiotensina II retarda, pero no evita, su progresión. La muerte celular contribuye a la pérdida de masa renal en las nefropatías crónicas. Un consorcio europeo empleó la transcriptómica en biopsias renales para identificar nuevos mediadores implicados en la muerte de la célula renal durante la nefropatía diabética. Un 25% de los genes relacionados con la muerte celular estaban expresados diferencialmente en la nefropatía diabética. TRAIL y osteoprotegerina fueron los genes más sobre expresados, y también estaba aumentado CD74. Las células tubulares y podocitos expresan TRAIL bajo la regulación de citocinas proinflamatorias(MIF vía CD74, TNF). La hiperglucemia sensibiliza a las células renales a la apoptosis inducida por TRAIL, mientras que la osteoprotegerina protege. Estos resultados sugieren que, además de la glucemia, la inflamación y TRAIL pueden ser objetivos terapéuticos en la nefropatía diabética (AU)

Diabetic nephropathy is the most common cause of end stage renal disease. Approaches targeting angiotensin II significantly delay its progression. However, many patients still need renal replacement therapy. High throughput techniques such as unbiased gene expression profiling and proteomics may identify new therapeutic targets. Cell death is thought to contribute to progressive renal cell depletion in chronic nephropathies. A European collaborative effort recently applied renal biopsy transcriptomics to identify novel mediators of renal cell death in diabetic nephropathy. Twenty-five percent of cell death regulatory genes were up or down regulated in diabetic kidneys. TNF-related apoptosis inducing ligand (TRAIL) and osteoprotegerin had the highest-level of expression. In diabetic nephropathy, tubular cells and podocytes express TRAIL. Inflammatory cytokines, including MIF via CD74, up regulate TRAIL. A high glucose environment sensitized renal cells to the lethal effect of TRAIL, while osteoprotegerin is protective. These results suggest that, in addition to glucose levels, inflammation and TRAIL are therapeutic targets in diabetic nephropathy (AU)

Modelos animales de diálisis peritoneal: relevancia, dificultades y futuro / No disponible

Los estudios realizados en biopsias peritoneales de pacientes con fallo renal que son tratados mediante diálisis peritoneal (DP) han demostrado que esta terapia provoca daños en la membrana peritoneal, caracterizados por fibrosisy angiogénesis, y que culminan en la pérdida de la capacidad de ultrafiltración de la membrana peritoneal. Estos estudios son descriptivos y apenas han contribuido al conocimiento de los mecanismos implicados en el proceso patológico inducido por la exposición de la membrana peritoneal a los líquidos de diálisis. Así, es necesario el desarrollo de modelos experimentales en animales para suplirlas deficiencias presentadas por los estudios en pacientes. Aquí tratamos las ventajas y dificultades de la utilización de modelos experimentales de diálisis peritoneal y las expectativas para el futuro (AU)

The studies performed with human peritoneal biopsies of peritonealdialysis-patients have demonstrated that exposure to peritonealdialysis fluid induce peritoneal deterioration. The main alterations of peritoneal membrane are fibrosis and angiogenesis that ends with the failure of the ultrafiltration capacity of the peritonealmembrane. These studies are descriptivist and scarcely help to investigate the mechanisms and stages involved on the process. Therefore, it is necessary to supply the deficiencies presented by the studies with patients. The experimental models have strongly contributed to the knowledge of the pathologic process that is induced by the continuous exposition of the peritonealmembrane to the dialysis fluids. Most of the peritonealdialysis studies use the rat as the experimental animal. Due to the difficulty of working with small animals, few studies have been done in mice. However, models in mice offers great advantages,as long as they allow us to employ different strains and genetically modified animals. We have recently developed an experimenta lmodel in mouse of exposure of the peritoneal membrane to dialysis fluids, which resembles the process of peritonealdamage that take place during peritoneal dialysis treatment inhuman patients (AU)

Apoptosis: from advances in PD to therapeutic targets in DM

A high glucose concentration is shared by peritoneal dialysis (PD)and diabetes mellitus (DM). High glucose leads to tissue injury indiabetes. Peritoneal dialysis research has emphasized the role of glucose degradation products in tissue injury. Apoptosis induction is one of the mechanisms of tissue injury induced both by glucose and glucose degradation products. We now review the role of apoptosis and its regulation by glucose degradation products in antibacterial defense and loss of renal function in diabetes mellitus and peritoneal dialysis. The pathogenic role of the recently identified glucose degradation product 3,4-di-deoxyglucosone-3-ene (3,4-DGE) is detailed. Available therapeutic strategies include the use of peritoneal dialysis solutions containing alow concentration of glucose degradation products. Based on preclinical results, specific targeting of apoptosis regulatory factor should be explored in the clinical setting (AU)

En la diálisis peritoneal (DP) y la diabetes mellitus (DM)altas concentraciones de glucosa se asocian a daño tisular. La apoptosis es uno de los mecanismos de daño tisular. Los productos de degradación de la glucosa (PDGs) se producen a partir de la glucosa tanto in vivo, en diabéticos, como durante el procesamiento de las soluciones de DP e inducen apoptosis en distintos tipos celulares. La apoptosises un modo activo de muerte celular con control molecular, regulada por moléculas intracelulares y extracelulares que dan lugar a distintas vías pro y antiapoptóticas, susceptibles de manipulación terapéutica. Entre estas se encuentran las caspasas, una familia de protein cisteasas que se comportan como moléculas iniciadoras o efectoras de la apoptosis. Entre los PDGs conocidos, la 3,4 dideoxiglucosona(3,4 DGE) es el principal componente letal de las soluciones de DP. La 3,4 DGE induce apoptosis en leucocitos y células tubulares de riñón. La inhibición de la apoptosis de leucocitos mejora la defensa antibacteriana peritoneal. Proponemos que los PDGs pueden estar implicados en el empeoramiento de la defensa antibacteriana y en lapérdida progresiva de la función renal en pacientes diabéticos y en DP. Entre las posibles estrategias terapéuticas destacamos el empleo de soluciones de DP con baja concentración de PDGs, que podrían disminuir la incidencia y gravedad de las peritonitis así como conservar la función renal residual. Otra posible estrategia seria el empleo de fármacos inhibidores de la apoptosis patológica (AU)

Bases teóricas para la propuesta de un ensayo clínicoaleatorizado, controlado y abierto, para evaluarla eficacia de la adición de bemiparina a la solución de icodextrina en pacientes en diálisis peritoneal con trastornos del transporte peritoneal[FRIAT-BEM-2005-01] / No disponible

Considerando todas las investigaciones realizadas hasta la fecha sobre las causas que contribuyen al deterioro de la membrana peritoneal y su fisiopatología, se puede concluir que es de gran interés investigar si la administración de heparinaintraperitoneal puede aportar un beneficio sobre el mantenimiento de la función peritoneal en los enfermos tratados con diálisis peritoneal (DP). Las acciones descritas a favor de esta idea son:1) La inflamación crónica del peritoneo es una causa de alteración de la función peritoneal y la heparina tiene acciónantiinflamatoria.2) La fibrosis peritoneal debida a diálisis peritoneal o a traumatismo puede ser evitada o mejorada con heparina ip.3) La heparina (HNF y HBPM, incluida bemiparina) indúcela síntesis de tPA por las células mesoteliales, lo que supone una acción fibrinolítica.4) La heparina, más la HBPM que la HNF, inhibe la angiogénesis.5) La heparina intraperitone al favorece la eliminación delos AGE en la DP.6) Modelos animales y estudios clínicos de corta extensión han demostrado una mejora de la función peritoneal con heparina.7) Por el momento, no se han encontrado problemas de seguridad en su administración intraperitoneal. Es por tanto una hipótesis verosímil que el uso de heparinaintraperitoneal puede modificar favorablemente la función peritoneal de pacientes en diálisis peritoneal (AU)

Multiple investigations performed on peritoneal pathophysiology during peritoneal dialysis (PD) suggest that intraperitonealheparin might modify most of the causes of membrane deterioration. The actions described favouring this idea are:1) Peritoneal Chronic inflammation alters peritoneal function and heprain has anti-inflammatory properties.2) Peritoneal fibrosis related to peritoneal dialysis or traumaticinjury may be avoided or limited with heparin.3) Heparine induces tPA síntesis by mesothelial cells, which represents a potentiation of fibrinolytic action.4) Heparine, sècifically low-molecular weight heparin, inhibitsangiogenesis.5) Intraperitoneal heparin favors the removal of advanced glycosilation end products in PD.6) Animal models and clinical studies with small series of patients have demonstrated an improvement of peritoneal function with intraperitoneal heparine use.7) Until now, no adverse effects of the intraperitoneal heparinuse have been found. In consequence, it is a plausible hipothesis to consider that intraperitonealheparin may favourably modify peritoneal function inpatients under peritoneal dialysis (AU)

TWEAK, el facilitador del daño renal agudo / No disponible

No disponible

Inflamación y aterotrombosis. Precocidad de la lesión vascular. Opciones diagnósticas y terapéuticas para prevención primaria / No disponible

La aterosclerosis, una enfermedad inflamatoria, se desarrolla precozmente en la ERC (Fuerza de Recomendación B). Por ello se plantea la indicación de la realización de pruebas para el diagnóstico de aterosclerosis subclínica y de inflamación sistémica.• Los pacientes con ERC tienen un alto riesgo vascular, lo que implica un tratamiento por objetivos de los factores de riesgo vascular.• En este contexto, se puede considerar la realización de pruebas de imagen para el diagnóstico de aterosclerosis subclínica a fin de individualizar las decisiones terapéuticas sobre el manejo de los factores de riesgo cardiovascular cuando el paciente no esté recibiendo ya un tratamiento consistente con el máximo nivel de riesgo (..) (AU)

Atherosclerosis, an inflammatory disease, develops prematurely in CKD (Strength of Recommendation B). The performance of tests for the diagnosis of subclinical atherosclerosis and systemic inflammation should therefore be considered in these patients.• Patients with CKD are at high risk of vascular disease, implying the need for goal-based treatment of the vascular riskfactors.• In this context, imaging tests for the diagnosis of subclinical atherosclerosis can be considered with the goal of individualizing treatment decisions on the management of cardiovascular risk factors when the patient is no longer receiving treatment consistent with the maximum risk level (..) (AU)

[Inflammation and atherothrombosis. Premature vascular injury. Diagnostic and therapeutic options for primary prevention]. / Inflamación y aterotrombosis. Precocidad de la lesión vascular. Opciones diagnósticas y terapéuticas para prevención primaria.

Atherosclerosis, an inflammatory disease, develops prematurely in CKD (Strength of Recommendation B). The performance of tests for the diagnosis of subclinical atherosclerosis and systemic inflammation should therefore be considered in these patients. - Patients with CKD are at high risk of vascular disease, implying the need for goal-based treatment of the vascular risk factors. - In this context, imaging tests for the diagnosis of subclinical atherosclerosis can be considered with the goal of individualizing treatment decisions on the management of cardiovascular risk factors when the patient is no longer receiving treatment consistent with the maximum risk level (Strength of Recommendation C). - The presence of subclinical atherosclerosis would raise cardiovascular risk to the maximum level (Strength of Recommendation C). - Carotid artery ultrasound with determination of carotid intima- media thickness (CIMT) and the presence of atheromatous plaques would be the technique of choice for the assessment of subclinical atherosclerosis in ACKD (Strength of Recommendation C). - C-reactive protein, measured by high-sensitivity assay (hs-CRP), is the only marker of inflammation used routinely in clinical practice. However, there is no evidence that routine determination of hs-CRP improves the outcomes of therapeutic decisions on cardiovascular protection in either the general population or ACKD population. Therefore, routine CRP determination cannot be recommended in patients with CKD to stratify their cardiovascular risk (Strength of Recommendation C).

[Animal models of peritoneal dialysis: relevance, difficulties, and future]. / Modelos animales de diálisis peritoneal: relevancia, dificultades y futuro.

The studies performed with human peritoneal biopsies of peritoneal dialysis -patients have demonstrated that exposure to peritoneal dialysis fluid induce peritoneal deterioration. The main alterations of peritoneal membrane are fibrosis and angiogenesis that ends with the failure of the ultrafiltration capacity of the peritoneal membrane. These studies are descriptivist and scarcely help to investigate the mechanisms and stages involved on the process. Therefore, it is necessary to supply the deficiencies presented by the studies with patients. The experimental models have strongly contributed to the knowledge of the pathologic process that is induced by the continuous exposition of the peritoneal membrane to the dialysis fluids. Most of the peritoneal dialysis studies use the rat as the experimental animal. Due to the difficulty of working with small animals, few studies have been done in mice. However, models in mice offers great advantages, as long as they allow us to employ different strains and genetically modified animals. We have recently developed an experimental model in mouse of exposure of the peritoneal membrane to dialysis fluids, which resembles the process of peritoneal damage that take place during peritoneal dialysis treatment in human patients.

Apoptosis: from advances in PD to therapeutic targets in DM.

A high glucose concentration is shared by peritoneal dialysis (PD) and diabetes mellitus (DM). High glucose leads to tissue injury in diabetes. Peritoneal dialysis research has emphasized the role of glucose degradation products in tissue injury. Apoptosis induction is one of the mechanisms of tissue injury induced both by glucose and glucose degradation products. We now review the role of apoptosis and its regulation by glucose degradation products in antibacterial defense and loss of renal function in diabetes mellitus and peritoneal dialysis. The pathogenic role of the recently identified glucose degradation product 3,4-di-deoxyglucosone- 3-ene (3,4-DGE) is detailed. Available therapeutic strategies include the use of peritoneal dialysis solutions containing a low concentration of glucose degradation products. Based on preclinical results, specific targeting of apoptosis regulatory factor should be explored in the clinical setting.

[Theoretical bases for the proposal of a randomized, controlled, open label clinical trial to assess the efficacy of adding bemiparin to the icodextrin solution in patients on peritoneal dialysis with peritoneal transport disorders [FRIAT-BEM-2005-01]]. / Bases teóricas para la propuesta de un ensayo clínico aleatorizado, controlado y abierto, para evaluar la eficacia de la adición de bemiparina a la solución de icodextrina en pacientes en diálisis peritoneal con trastornos del transporte peritoneal [FRIAT-BEM-2005-01].

Multiple investigations performed on peritoneal pathophysiology during peritoneal dialysis (PD) suggest that intraperitoneal heparin might modify most of the causes of membrane deterioration. The actions described favouring this idea are: 1) Peritoneal Chronic inflammation alters peritoneal function and hepraine has anti-inflammatory properties. 2) Peritoneal fibrosis related to peritoneal dialysis or traumatic injury may be avoided or limited with heparin. 3) Heparine induces tPA synthesis by mesothelial cells, which represents a potentiation of fibrinolytic action. 4) Heparine, specifically low-molecular weight heparin, inhibits angiogenesis. 5) Intraperitoneal heparin favors the removal of advanced glycosilation end products in PD. 6) Animal models and clinical studies with small series of patients have demonstrated an improvement of peritoneal function with intraperitoneal heparine use. 7) Until now, no adverse effects of the intraperitoneal heparin use have been found. In consequence, it is a plausible hypothesis to consider that intraperitoneal heparin may favourably modify peritoneal function in patients under peritoneal dialysis.