RESUMEN
Sclerosing encapsulating peritonitis is a very rare pathological entity. It is a chronic fibroinflammatory disease affecting the peritoneum and leading to the formation of diffuse egg-shell-shaped fibrous capsule which totally or locally encapsulate the abdominal viscera, in particular the digestive tract. Clinical signs are little specific and misleading. Medical imaging, including computed tomography, can help clinicians to make a diagnosis, by highlighting a thin peritoneal membrane encompassing an agglutination of digestive loops. Secondary types (postperitoneal dialysis, tuberculosis, medications, postintraperitoneal chemotherapy) are quite common, however idiopathic sclerosing encapsulating peritonitis is very rare and few cases have been reported in the literature. We here report the case of a 53-year-old woman with idiopathic sclerosing encapsulating peritonitis.
Asunto(s)
Fibrosis Peritoneal/diagnóstico por imagen , Peritoneo/diagnóstico por imagen , Peritonitis/diagnóstico por imagen , Femenino , Humanos , Persona de Mediana Edad , Fibrosis Peritoneal/fisiopatología , Peritoneo/fisiopatología , Peritonitis/fisiopatología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Encapsulating-peritoneal-sclerosis (EPS) is a rare, but serious and life-threatening complication of peritoneal dialysis (PD). Treatment of EPS consists of discontinuation of PD and maintenance of nutritional status, whereas the role of corticosteroids, tamoxifen and other immunosuppresive agents is not yet fully elucidated. CASE-PRESENTATION: We report the case of a 28-year-old patient, who developed a severe form of calcifying EPS after a 6-year-long therapy with automated PD. The clinical presentation was severe with repeated episodes of total bowel obstruction, weight loss and malnutrition that mandated his prolonged hospitalization. Initial treatment included corticosteroids and tamoxifen (20 mg/day) with a clinically meaningful improvement in gastrointestinal function and nutritional status over the first 6-12 months. Corticosteroids were discontinued at 18 months, but owing to persistence of calcifying lesions and peritoneal thickening in repeated computed-tomography (CT) scans, tamoxifen remained unmodified at a low-dose of 20 mg/day for a 10-year-long period. During follow-up, the patient remained symptoms-free in an excellent clinical condition and the CT findings were unchanged. CONCLUSIONS: Long-term administration of tamoxifen was not accompanied by any drug-related adverse effects and potentially exerted a beneficial action on down-regulation of inflammatory and fibrotic processes and improvement of gastrointestinal function, nutritional status and overall health-related quality of life.
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Calcinosis , Obstrucción Intestinal , Diálisis Peritoneal/efectos adversos , Fibrosis Peritoneal , Calidad de Vida , Tamoxifeno/administración & dosificación , Corticoesteroides/administración & dosificación , Adulto , Antiinflamatorios/administración & dosificación , Antineoplásicos/administración & dosificación , Calcinosis/tratamiento farmacológico , Calcinosis/etiología , Calcinosis/terapia , Humanos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/terapia , Fallo Renal Crónico/terapia , Cuidados a Largo Plazo/métodos , Masculino , Desnutrición/etiología , Desnutrición/terapia , Diálisis Peritoneal/métodos , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/fisiopatología , Fibrosis Peritoneal/psicología , Fibrosis Peritoneal/terapia , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Pérdida de PesoRESUMEN
BACKGROUND Long-term exposure to hypertonic and high glucose in peritoneal dialysis fluid can result in peritoneal fibrosis. Spleen tyrosine kinase (SYK) has a role in inflammation and fibrosis. This study aimed to investigate the role of SYK in an in vivo rat model of peritoneal fibrosis and in rat peritoneal mesothelial cells (PMCs) in vitro and to investigate the underlying mechanisms. MATERIAL AND METHODS Sprague-Dawley rats (N=24) were randomized into the sham control group (N=6); the peritoneal fibrosis group (N=6) treated with intraperitoneal chlorhexidine digluconate; the SYK inhibitor group (N=6), treated with chlorhexidine digluconate and fostamatinib; and the TGF-ß inhibitor group (N=6), treated with chlorhexidine digluconate and LY2109761. The rat model underwent daily intraperitoneal injection with 0.5 ml of 0.1% chlorhexidine digluconate. Rat peritoneal mesothelial cells (PMCs) were cultured in vitro in high glucose. SYK expression was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR measured inflammatory mediators. Transforming growth factor-ß1 (TGF-ß1) and Smad3 were detected by Western blot. Short hairpin RNA (shRNA) was used to target the SYK gene. RESULTS SYK was upregulated in the rat model of peritoneal fibrosis and was induced rat PMCs cultured in high glucose. Knockdown of SYK and inhibition of TGF-ß1 significantly reduced fibrosis and inflammation. Findings in the in vivo rat model confirmed that SYK mediated peritoneal fibrosis by regulating TGF-ß1/Smad3 signaling. CONCLUSIONS In a rat model and in rat PMCs, expression of SYK increased peritoneal fibrosis through activation of the TGF-ß1/Smad3 signaling pathway.
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Fibrosis Peritoneal/metabolismo , Quinasa Syk/metabolismo , Animales , China , Clorhexidina/análogos & derivados , Clorhexidina/farmacología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Diálisis Peritoneal , Fibrosis Peritoneal/fisiopatología , Peritoneo/patología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/fisiología , Proteína smad3/metabolismo , Quinasa Syk/fisiología , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
AIM: To investigate the efficacy of adalimumab treatment in an experimental rat sclerosing encapsulated peritonitis (SEP) model. METHODS: The study involved 40 Wistar albino rats divided into four groups: chlorhexidine (CH) group, control group, CH + adalimumab group, and CH + resting group. The control group received normal saline intraperitoneally (i.p.). Other groups received 0.1% CH gluconate, 15% ethanol, and normal saline mixture i.p. for three weeks in order to induce SEP. CH + adalimumab group received 5 mg/kg adalimumab i.p. at the beginning of week 4 and week 6, while CH + resting group was followed-up for three weeks without applying any procedure after the onset of SEP. Rats in groups CH and control group were sacrificed on day 21, and rats in group CH + adalimumab and CH + resting were sacrificed on day 42. All groups were evaluated for peritoneal thickness, inflammation, vascularization, and fibrosis. RESULTS: CH + adalimumab group showed a significant decrease in peritoneal thickness, fibrosis score, and vascular score compared with CH group and CH + resting group. CONCLUSION: Adalimumab can prevent SEP development.
Asunto(s)
Adalimumab/uso terapéutico , Antiinflamatorios/uso terapéutico , Fibrosis Peritoneal/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Fibrosis Peritoneal/patología , Fibrosis Peritoneal/fisiopatología , Ratas , Ratas WistarRESUMEN
Peritoneal fibrosis is recognised as the main cause of the technical failure of peritoneal dialysis (PD), and currently, there are no specific and effective anti-fibrosis therapies. We have found that miR-200a is down-regulated in a rat model of PD-related peritoneal fibrosis (PF) and could inhibit transforming growth factor beta 1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) in peritoneal mesothelial cells by target ZEB1/2. However, its treatment role in vivo is still largely unclear. In this study, we examined the therapeutic potential for miR-200a on PD-related PF in a rat model of PD induced by daily infusion of 4.25% dextrose-containing dialysate. Male Sprague-Dawley rats were divided into four groups: control group, PD group, PD + miR-agomir-NC group, and PD + miR-200a-agomir group (n = 5 in each group). MiR-200a agomir was delivered into the peritoneum by intra-peritoneal injection on days 10 and 20 after PD. We found that treatment with miR-200a agomir significantly reduced the collagen volume fraction (CVF) of the peritoneum and prevented peritoneal dysfunction. The up-regulation of the EMT marker (decreased E-cadherin and increased α-smooth muscle actin) and extracellular matrix (fibronectin and collagen I) was significantly ameliorated by miR-200a in the PD + miR-200a-agomir group. Furthermore, we demonstrated that miR-200a inhibition of PF in vivo was associated with the suppression of ZEB1 and 2, which were proved to be the target of miR-200a in our previous study. In conclusion, results from the present study suggest that treatment with miR-200a may represent a novel and effective therapy for PD-related PF.
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MicroARNs/uso terapéutico , Diálisis Peritoneal , Fibrosis Peritoneal/terapia , Animales , Modelos Animales de Enfermedad , Masculino , Diálisis Peritoneal/efectos adversos , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/fisiopatología , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
Peritoneal dialysis (PD) is often used to treat patients with end stage renal disease, and its long-term complications include excessive inflammation and oxidative stress. Allograft inflammatory factor 1 (AIF-1), as a cytoplasmic protein, is originally identified from infiltrating macrophages, and it was associated with inflammation in the cells other than macrophages, such as endothelial cells and vascular smooth muscle cells. To clarify the molecular mechanisms of AIF-1-modulated pathological changes in the peritoneum during PD, we first detected the AIF-1 expression in peritoneal tissues from PD mice. Results revealed that the pro-fibrotic stimulation caused AIF-1 upregulation and triggered inflammation in peritoneal tissues, and that AIF-1 co-expressed with pan-cytokeratin (a marker of peritoneal mesothelial cells). We next treated primary mouse peritoneal mesothelial cells (pan-cytokeratin and intercellular adhesion molecule 1 positive cells) with 50 or 100 ng/mL recombinant AIF-1, and evaluated the direct effects of AIF-1 on these cells in vitro. We found that exogenous AIF-1 treatment induced inflammation and oxidative stress in mesothelial cells. Apart from the augmented IL-6 and TNF-α secretion, the level of ROS was upregulated and the activity of anti-oxidative SOD was reduced in cells exposed to AIF-1. Moreover, AIF-1 simulation triggered the activation of NF-κB pathway-enhanced the conversion of IκB to phosphorylated IκB and promoted the translocation of NF-κB p65 from cytoplasm into nucleus. Additionally, AIF-1-evoked inflammation in peritoneal mesothelial cells was attenuated by the addition of NF-κB inhibitor (BAY 11-7082). In brief, this study provides us novel information to understand the molecular regulation mechanisms of AIF-1 in peritoneal fibrosis.
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Proteínas de Unión al Calcio/fisiología , Proteínas de Microfilamentos/fisiología , Fibrosis Peritoneal/metabolismo , Peritoneo/metabolismo , Aloinjertos/inmunología , Animales , Proteínas de Unión al Calcio/metabolismo , Células Epiteliales/metabolismo , Fibrosis/metabolismo , Proteínas I-kappa B/metabolismo , Inflamación/metabolismo , Queratinas/análisis , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas de Microfilamentos/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo/fisiología , Diálisis Peritoneal/efectos adversos , Fibrosis Peritoneal/fisiopatología , Peritoneo/fisiología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Transcripción ReIA/metabolismoRESUMEN
BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of long-term peritoneal dialysis (PD). However, previous studies reported large variations in its mortality rates that may associate with a different degree of EPS severity. This study reports the incidence and outcomes of EPS and identifies the risk factors associated with severe EPS. METHODS: We retrospectively analyzed clinical data of EPS patients from 3 medical centers in Taiwan from January 1982 to September 2015, and classified patients as having mild/moderate or severe EPS. Patients with intractable intestinal obstruction/gut-related sepsis that needed surgical intervention or resulted in mortality were in severe EPS group. Follow-up for outcome was through December 31, 2015. Clinical characteristics, peritoneal dialysis (PD)-related parameters, biochemical and imaging results were analyzed and compared between groups. RESULTS: Fifty-eight of 3202 patients undergoing PD during the study period had EPS (prevalence 1.8%). The incidence of EPS increased for patients on PD for >6-8 years (≤6 yrs. vs. >6-8 yrs., 0.0% vs. 1.8%, p = 0.001). Relative to those on PD for >6-8 years, the risk of EPS significantly increased with PD duration longer than 10 years (>10-12 years vs. >6-8 years: OR: 5.5, 95% CI: 1.7-17.1, p < 0.01). Twenty-three patients fulfilled the criteria for severe EPS. The overall mortality rate of EPS was 35% (20/58), and was 74% (17/23) in the severe EPS group. The average serum levels of C-reactive protein (CRP) and intact-parathyroid hormone (i-PTH), which were checked every 3~6 months within one year before diagnosis of EPS, were higher in severe EPS group than in mild/moderate group (p = 0.02, p = 0.08, respectively). Multivariate analysis revealed severe EPS was independently associated with bowel tethering (based on CT), presentation with bloody ascites, diagnosis of EPS after withdrawal from PD, and i-PTH ≥ 384 pg/mL. Receiver operating characteristic analysis indicated that presentation with 2 or more of the 5 risk factors (EPS diagnosis after PD withdrawal, bloody ascites, bowel tethering, CRP ≥ 29 mg/L, and i-PTH ≥ 384 pg/mL) had a good accuracy (AUC = 0.80, p = 0.001) for prediction of severe EPS. CONCLUSIONS: The incidence of EPS increases with PD duration. Severe EPS has high mortality rate and is associated with bowel tethering, presentation of bloody ascites, diagnosis after PD withdrawal, and higher serum levels of i-PTH before EPS diagnosis. Having 2 or more of the 5 risk factors can provide a good accuracy for prediction of severe EPS.
Asunto(s)
Fibrosis Peritoneal/fisiopatología , Adulto , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Fibrosis Peritoneal/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Taiwán/epidemiologíaRESUMEN
Peritoneal dialysis (PD) is an established form of renal replacement therapy. Long-term PD leads to morphologic and functional changes to the peritoneal membrane (PM), which is defined as peritoneal fibrosis, a known cause of loss of peritoneal ultrafiltration capacity. Inflammation and angiogenesis are key events during the pathogenesis of peritoneal fibrosis. This review discusses the pathophysiology of peritoneal fibrosis and recent research progress on key fibrogenic molecular mechanisms in peritoneal inflammation and angiogenesis, including Toll-like receptor ligand-mediated, NOD-like receptor protein 3/interleukin-1ß, vascular endothelial growth factor, and angiopoietin-2/Tie2 signaling pathways. Furthermore, novel strategies targeting peritoneal inflammation and angiogenesis to preserve the PM are discussed in depth.
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Neovascularización Patológica/fisiopatología , Diálisis Peritoneal/efectos adversos , Fibrosis Peritoneal/prevención & control , Fibrosis Peritoneal/fisiopatología , Peritonitis/metabolismo , Humanos , Fibrosis Peritoneal/etiología , Peritonitis/etiología , Transducción de SeñalRESUMEN
The peritoneum defines a confined microenvironment, which is stable under normal conditions, but is exposed to the damaging effect of infections, surgical injuries, and other neoplastic and non-neoplastic events. Its response to damage includes the recruitment, proliferation, and activation of a variety of haematopoietic and stromal cells. In physiological conditions, effective responses to injuries are organized; inflammatory triggers are eliminated; inflammation quickly abates; and the normal tissue architecture is restored. However, if inflammatory triggers are not cleared, fibrosis or scarring occurs and impaired tissue function ultimately leads to organ failure. Autoimmune serositis is characterized by the persistence of self-antigens and a relapsing clinical pattern. Peritoneal carcinomatosis and endometriosis are characterized by the persistence of cancer cells or ectopic endometrial cells in the peritoneal cavity. Some of the molecular signals orchestrating the recruitment of inflammatory cells in the peritoneum have been identified in the last few years. Alternative activation of peritoneal macrophages was shown to guide angiogenesis and fibrosis, and could represent a novel target for molecular intervention. This review summarizes current knowledge of the alterations to the immune response in the peritoneal environment, highlighting the ambiguous role played by persistently activated reparative macrophages in the pathogenesis of common human diseases. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Asunto(s)
Enfermedades Peritoneales/fisiopatología , Peritoneo/fisiología , Enfermedades Autoinmunes/etiología , Endometriosis/etiología , Endometriosis/inmunología , Endometriosis/fisiopatología , Femenino , Humanos , Inmunidad Celular/fisiología , Enfermedades Peritoneales/etiología , Enfermedades Peritoneales/inmunología , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/inmunología , Fibrosis Peritoneal/fisiopatología , Neoplasias Peritoneales/etiología , Neoplasias Peritoneales/inmunología , Neoplasias Peritoneales/fisiopatología , Peritoneo/anatomía & histología , Peritoneo/inmunología , Peritonitis/etiología , Peritonitis/patología , Peritonitis/fisiopatología , Serositis/etiología , Cicatrización de Heridas/fisiologíaRESUMEN
INTRODUCTION: This study aimed to investigate the effects of erythropoiesis-stimulating agents (ESAs) on intestinal flora in peritoneal fibrosis. METHODS AND METHODS: Twenty-four Wistar albino rats were divided into 3 groups as the control group, which received 0.9% saline (3 mL/d) intraperitoneally; the chlorhexidine gluconate (CH) group, which received 3 mL/d injections of 0.1% CH intraperitoneally, and the ESA group, which received 3 mL/d injections of 0.1% CH intraperitoneally and epoetin beta (3 doses of 20 IU/kg/wk) subcutaneously. On the 21st day, the rats were sacrificed and the visceral peritoneum samples were obtained from left liver bowel. Blood samples were obtained from abdominal aorta and intestinal flora samples were obtained from transverse colon. RESULTS: Histopathologically, the CH, ESA, and control groups had peritoneal thickness of 135.4 ± 22.2 µm, 48.6 ± 12.8 µm, and 6.0 ± 2.3 µm, respectively. Escherichia coli was the predominant bacterium in the intestinal flora in the control group. Significant changes in microbial composition of intestinal flora towards Proteus species and Enterobacter species was seen among the groups (P < .001). There was no significant difference between the ESA and CH groups regarding the isolates from blood cultures. However, the bacterial isolates from cultures of intestinal flora among these groups were significantly different (P < .05). CONCLUSIONS: Erythropoiesis-stimulating agents change intestinal flora by a clinically significant amount in experimental peritoneal fibrosis. We consider that ESAs achieve this via regulating intestinal peristaltism.
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Bacterias/efectos de los fármacos , Eritropoyetina/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Hematínicos/farmacología , Intestinos/efectos de los fármacos , Fibrosis Peritoneal/tratamiento farmacológico , Animales , Bacterias/clasificación , Bacterias/crecimiento & desarrollo , Clorhexidina/análogos & derivados , Modelos Animales de Enfermedad , Femenino , Intestinos/microbiología , Intestinos/fisiopatología , Peristaltismo/efectos de los fármacos , Fibrosis Peritoneal/inducido químicamente , Fibrosis Peritoneal/microbiología , Fibrosis Peritoneal/fisiopatología , Ratas Wistar , Proteínas Recombinantes/farmacologíaRESUMEN
Peritoneal membrane failure (PMF) and, ultimately, encapsulating peritoneal sclerosis (EPS) are the most serious peritoneal dialysis (PD) complications. Combining clinical and peritoneal transport data with the measurement of molecular biomarkers, such as the chemokine CCL18, would improve the complex diagnosis and management of PMF. We measured CCL18 levels in 43 patients' effluent and serum at baseline and after 1, 2, and 3 years of PD treatment by retrospective longitudinal study, and evaluated their association with PMF/EPS development and peritoneal risk factors. To confirm the trends observed in the longitudinal study, a cross-sectional study was performed on 61 isolated samples from long-term (more than 3 years) patients treated with PD. We observed that the patients with no membrane dysfunction showed sustained low CCL18 levels in peritoneal effluent over time. An increase in CCL18 levels at any time was predictive of PMF development (final CCL18 increase over baseline, p = .014; and maximum CCL18 increase, p = .039). At year 3 of PD, CCL18 values in effluent under 3.15 ng/ml showed an 89.5% negative predictive value, and higher levels were associated with later PMF (odds ratio 4.3; 95% CI 0.90-20.89; p = .067). Moreover, CCL18 levels in effluent at year 3 of PD were independently associated with a risk of PMF development, adjusted for the classical (water and creatinine) peritoneal transport parameters. These trends were confirmed in a cross-sectional study of 61 long-term patients treated with PD. In conclusion, our study shows the diagnostic capacity of chemokine CCL18 levels in peritoneal effluent to predict PMF and suggests CCL18 as a new marker and mediator of this serious condition as well as a new potential therapeutic target.
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Quimiocinas CC/metabolismo , Fibrosis Peritoneal/fisiopatología , Peritoneo/fisiopatología , Adulto , Anciano , Biomarcadores/metabolismo , Creatinina/metabolismo , Estudios Transversales , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Diálisis Peritoneal/métodos , Fibrosis Peritoneal/metabolismo , Peritoneo/metabolismo , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
Early innovations in the delivery of peritoneal dialysis (PD) markedly improved its acceptability and lowered peritonitis rates. The standard osmotic agent was, and continues to be dextrose, an agent that is not ideal as it is readily absorbed. The development of icodextrin-containing dialysis fluid has allowed a long dwell time to provide more effective ultrafiltration. The development of a smaller, more easily used automated cycler, led to an increase in the proportion of patients on the cycler as opposed to CAPD. Recently, new cyclers with better teaching tools and ease of use and communication with the training team have come on the market; data on outcomes using these cyclers are not yet available. Peritonitis continues to be a serious complication of PD although improvements in connectology and research on Staphylococcus aureus carriage have decreased peritonitis risk. Peritonitis rates continue to vary tremendously from one program to another, which may be in part due to failure to follow best demonstrated practices in training, care of the l catheter exit site, and prevention of peritonitis. Peritonitis rates should be expressed as episodes per year at risk and as organism-specific rates to allow comparisons from one program to another, from one period to another and from a program to the published literature. The term technique failure is misused in PD. Patients leave PD for a host of reasons including transplantation. Transfer from PD to hemodialysis can be planned and have an excellent outcome or can be delayed or done emergently and have a less optimal outcome. The life plan of the patient with ESRD needs to be not only considered but also periodically revised as circumstances and patient wishes change.
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Fallo Renal Crónico/terapia , Evaluación de Resultado en la Atención de Salud , Cooperación del Paciente/estadística & datos numéricos , Diálisis Peritoneal Ambulatoria Continua/métodos , Peritonitis/etiología , Infecciones Estafilocócicas/epidemiología , Infecciones Relacionadas con Catéteres/epidemiología , Infecciones Relacionadas con Catéteres/microbiología , Causas de Muerte , Soluciones para Diálisis/farmacología , Femenino , Humanos , Incidencia , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/mortalidad , Masculino , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/mortalidad , Fibrosis Peritoneal/fisiopatología , Peritonitis/fisiopatología , Peritonitis/terapia , Medición de Riesgo , Índice de Severidad de la Enfermedad , Infecciones Estafilocócicas/etiología , Infecciones Estafilocócicas/fisiopatología , Análisis de Supervivencia , Estados UnidosRESUMEN
This report reviews the most common surgical interventions and complications of chronic peritoneal dialysis (PD) patients. Based on the current knowledge as well as our experience we detail the role of these surgical procedures. We supplement the reported knowledge in the field with our own experience in this area. The areas discussed include early complications such as surgical wound hemorrhage, bleeding from the catheter, intestinal perforation and urinary bladder perforation, dialysate leakage through the wound, as well as late complications including catheter kinking or occlusion, retention of fluid in the peritoneal recess, hernias and hydrothorax, and encapsulating peritoneal sclerosis. We also briefly cover the surgical aspects of exit-site infection and peritonitis. An understanding by nephrologists of the role for surgical intervention in PD patients will improve their care and outcomes.
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Infecciones Relacionadas con Catéteres/cirugía , Catéteres de Permanencia/efectos adversos , Diálisis Peritoneal/efectos adversos , Fibrosis Peritoneal/cirugía , Peritonitis/cirugía , Infecciones Relacionadas con Catéteres/fisiopatología , Soluciones para Diálisis/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Hidrotórax/etiología , Hidrotórax/cirugía , Masculino , Diálisis Peritoneal/métodos , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Diálisis Peritoneal Ambulatoria Continua/métodos , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/fisiopatología , Peritonitis/etiología , Peritonitis/fisiopatología , Calidad de Vida , Medición de Riesgo , Resultado del TratamientoRESUMEN
Objective: To investigate the role of glucose transporter 1 (GLUT1) and sodium-glucose cotransporter 1 (SGLT1) in high glucose dialysate-induced peritoneal fibrosis. Methods: Thirty six male SD rats were randomly divided into 6 groups (6 in each):normal control group, sham operation group, peritoneal dialysis group (PD group), PD+phloretin group (PD+T group), PD+phlorizin group (PD+Z group), PD+phloretin+phlorizin group (PD+T+Z group). Rat model of uraemia was established using 5/6 nephrotomy, and 2.5% dextrose peritoneal dialysis solution was used in peritoneal dialysis. Peritoneal equilibration test was performed 24 h after dialysis to evaluate transport function of peritoneum in rats; HE staining was used to observe the morphology of peritoneal tissue; and immunohistochemistry was used to detect the expression of GLUT1, SGLT1, TGF-ß1 and connective tissue growth factor (CTGF) in peritoneum. Human peritoneal microvascular endothelial cells (HPECs) were divided into 5 groups:normal control group, peritoneal dialysis group (PD group), PD+phloretin group (PD+T group), PD+phlorezin group (PD+Z group), and PD+phloretin+phlorezin group (PD+T+Z group). Real time PCR and Western blotting were used to detect mRNA and protein expressions of GLUT1, SGLT1, TGF-ß1, CTGF in peritoneal membrane and HPECs. Results:In vivo, compared with sham operation group, rats in PD group had thickened peritoneum, higher ultrafiltration volume, and the mRNA and protein expressions of GLUT1, SGLT1, CTGF, TGF-ß1 were significantly increased (all P<0.05); compared with PD group, thickened peritoneum was attenuated, and the mRNA and protein expressions of GLUT1, SGLT1, CTGF, TGF-ß1 were significantly decreased in PD+T, PD+Z and PD+T+Z groups (all P<0.05). Pearson's correlation analysis showed that the expressions of GLUT1, SGLT1 in peritoneum were positively correlated with the expressions of TGF-ß1 and CTGF (all P<0.05). In vitro, the mRNA and protein expressions of GLUT1, SGLT1, TGF-ß1, CTGF were significantly increased in HPECs of peritoneal dialysis group (all P<0.05), and those in PD+T, PD+Z, and PD+T+Z groups were decreased (all P<0.05). Pearson's correlation analysis showed that the expressions of GLUT1, SGLT1 in HPECs were positively correlated with the expressions of TGF-ß1 and CTGF (all P<0.05). Conclusion: High glucose peritoneal dialysis fluid may promote peritoneal fibrosis by upregulating the expressions of GLUT1 and SGLT1.
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Soluciones para Diálisis/efectos adversos , Soluciones para Diálisis/farmacología , Transportador de Glucosa de Tipo 1/efectos de los fármacos , Transportador de Glucosa de Tipo 1/fisiología , Glucosa/efectos adversos , Glucosa/farmacología , Hemodiafiltración/efectos adversos , Hemodiafiltración/métodos , Diálisis Peritoneal/efectos adversos , Diálisis Peritoneal/métodos , Fibrosis Peritoneal/inducido químicamente , Fibrosis Peritoneal/genética , Peritoneo/química , Peritoneo/efectos de los fármacos , Peritoneo/patología , Transportador 1 de Sodio-Glucosa/efectos de los fármacos , Transportador 1 de Sodio-Glucosa/fisiología , Uremia/inducido químicamente , Animales , Células Cultivadas , Factor de Crecimiento del Tejido Conjuntivo/análisis , Factor de Crecimiento del Tejido Conjuntivo/efectos de los fármacos , Soluciones para Diálisis/química , Regulación de la Expresión Génica/efectos de los fármacos , Transportador de Glucosa de Tipo 1/análisis , Humanos , Masculino , Fibrosis Peritoneal/fisiopatología , Floretina , Florizina , ARN Mensajero , Ratas , Ratas Sprague-Dawley , Transportador 1 de Sodio-Glucosa/análisis , Factor de Crecimiento Transformador beta1/análisis , Factor de Crecimiento Transformador beta1/efectos de los fármacosRESUMEN
BACKGROUND: Peritoneal dialysis (PD) can induce fibrosis and functional alterations in PD patients' peritoneal membranes, due to long-term unphysiological dialysate exposure, partially occurring via triggering of epithelial-to-mesenchymal transition (EMT) in peritoneal mesothelial cells (MCs). Vitamin D can ameliorate these negative effects; however, the mechanism remains unexplored. Therefore, we investigated its possible links to MCs EMT inhibition. METHODS: Peritoneal fibrosis was established in Sprague-Dawley rats by chlorhexidine gluconate (CG) intraperitoneal injection for 21 days, with and without 1α,25(OH)2D3 treatment. Morphological and functional evaluation and western blot analysis of EMT marker were performed upon peritoneum tissue. In vitro study was also performed in a primary human peritoneal MC culture system; MCs were incubated with transforming growth factor-ß1 (TGF-ß1) in the absence or presence of 1α,25(OH)2D3. EMT marker expression, migration activities, and cytoskeleton redistribution of MCs were determined. RESULTS: 1α,25(OH)2D3 ameliorated CG-induced morphological and functional deterioration in animal model, along with CG-induced upregulation of α-SMA and downregulation of E-cadherin expression. Meanwhile, 1α,25(OH)2D3 also ameliorated TGF-ß1-induced decrease in E-cadherin expression, increase in Snai1 and α-SMA expression, intracellular F-actin redistribution, and migration activity in vitro. CONCLUSION: 1α,25(OH)2D3 can ameliorate CG-induced peritoneal fibrosis and attenuate functional deterioration through inhibiting MC EMT.
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Transición Epitelial-Mesenquimal/efectos de los fármacos , Epitelio/efectos de los fármacos , Fibrosis Peritoneal/prevención & control , Fibrosis Peritoneal/fisiopatología , Vitamina D/administración & dosificación , Animales , Células Cultivadas , Clorhexidina/análogos & derivados , Relación Dosis-Respuesta a Droga , Epitelio/patología , Epitelio/fisiopatología , Humanos , Masculino , Fibrosis Peritoneal/inducido químicamente , Ratas , Ratas Sprague-Dawley , Resultado del TratamientoRESUMEN
Loss of peritoneal function due to peritoneal fibrosing syndrome (PFS) is a major factor leading to treatment failure in chronic peritoneal dialysis (PD) patients. Although the precise biologic mechanisms responsible for these changes have not been defined, the general assumption is that alterations in peritoneal function are related to structural changes in the peritoneal membrane. Studies of the peritoneal membrane by non-invasive ultrasonography (US) in chronic PD patients are limited. The aim of the present study is to assess the relationship between functional parameters of peritoneum and peritoneal thickness measured by US in children treated by chronic PD. We recruited two groups of patients: 23 subjects (13 females, 10 males) on chronic PD (patient group) and 26 (7 females, 19 males) on predialysis out-patient follow-up (creatinine clearance: 20-60 mL/min/1.73 m(2)) (control group). Age, sex, weight, height, body mass index (BMI), chronic PD duration, episodes of peritonitis and the results of peritoneal equilibration test (PET) were recorded. Hemoglobin (Hb), blood pressure (BP), left ventricular mass index (LVMI) and renal osteodystrophy (ROD) parameters were also obtained. The thickness of the parietal peritoneum was measured by trans-abdominal US in all children. Statistical analyses were performed by using Student's t and Pearson's correlation tests. Mean peritoneal thickness in chronic PD patients (1028.26 ± 157.26 µm) was significantly higher than control patients (786.52 ± 132.33). Mean peritoneal thickness was significantly correlated with mean body height (R(2) = 0.93, p < 0.05), BMI (R(2) = 0.25, p < 0.05), chronic PD duration (R(2) = 0.64, p < 0.05), episodes of peritonitis (R(2) = 0.93, p < 0.05), D/Pcreatinine (R(2) = 0.76, p < 0.05) and D4/D0glucose (R(2) = 0.81, p < 0.05). No correlation was found between peritoneal thickness and Hb, BP, LVMI and ROD parameters. In conclusion, ultrasonographic measurement of peritoneal membrane thickness is a simple and non-invasive method in chronic PD children. This diagnostic tool likely enables to assess peritoneal structure and function in these patients.
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Fallo Renal Crónico/terapia , Fibrosis Peritoneal , Peritoneo , Adolescente , Antropometría/métodos , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Diálisis Peritoneal/efectos adversos , Diálisis Peritoneal/métodos , Fibrosis Peritoneal/diagnóstico por imagen , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/fisiopatología , Peritoneo/diagnóstico por imagen , Peritoneo/fisiopatología , Reproducibilidad de los Resultados , Insuficiencia del Tratamiento , Turquía , UltrasonografíaRESUMEN
UNLABELLED: ⦠INTRODUCTION: Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis in which gastrointestinal (GI) symptoms reduce appetite and dietary intake. Adequate nutrition is important, especially if surgery is required. Although the incidence of EPS is low, the present report is able to detail preoperative nutrition status and treatment in a large cohort of patients from a national EPS referral center. ⦠METHODS: Of 51 patients admitted to this EPS specialist center hospital for their first peritonectomy in the study period, 50 had a preoperative dietetic assessment, and 49 underwent upper-arm anthropometry. ⦠RESULTS: Mean body mass index (BMI) was 20.6 kg/m(2). Mean weight loss was 14% of body weight in the preceding 6 months, with 35 of 50 patients losing more than 10%. On anthropometry, 25 of 49 patients were below the 5th percentile for mid-arm circumference (MAC), 17 of 49 were below for triceps skinfold thickness (TSF), and 21 of 49 were below for mid-arm muscle circumference (MAMC). Mean handgrip strength (HGS) was 60% of normal, with 43 of 49 patients being below 85% of normal. Appetite was poor in 21 of 50 patients, and 37 of 50 had upper and 40 of 50 had lower GI symptoms. By subjective global assessment, 27 of 51 patients were graded as severely malnourished, and 5 of 51, as well-nourished. Mean serum albumin was 28 g/L and did not correlate with BMI, MAC, TSF, MAMC, or HGS. In most patients, C-reactive protein was elevated (mean: 111 mg/L). Preoperative parenteral nutrition was given to 46 of 51 patients for a mean of 21 days. ⦠DISCUSSION: Our findings demonstrate the poor nutrition status of patients admitted for EPS surgical intervention. Anthropometrics reveal depleted fat and lean body mass in EPS patients, which might be a result of anorexia and inflammation, and the reason that albumin was not an accurate marker of nutrition. Poor nutrition status is likely to negatively affect outcome in this patient group. ⦠CONCLUSIONS: Early recognition of GI symptoms may herald a diagnosis of EPS. Optimization of preoperative nutrition status with intensive nutrition support is needed.
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Antropometría , Diálisis Peritoneal/efectos adversos , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/cirugía , Síndrome Debilitante/etiología , Síndrome Debilitante/mortalidad , Adulto , Anciano , Índice de Masa Corporal , Peso Corporal , Estudios de Cohortes , Nutrición Enteral/métodos , Femenino , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Evaluación Nutricional , Estado Nutricional , Diálisis Peritoneal/métodos , Fibrosis Peritoneal/fisiopatología , Peritoneo/cirugía , Cuidados Posoperatorios/métodos , Cuidados Preoperatorios , Medición de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento , Síndrome Debilitante/terapia , Adulto JovenRESUMEN
Encapsulating peritoneal sclerosis (EPS) involves excessive peritoneal fibrosis in patients on peritoneal dialysis, eventually leading to visceral constriction and bowel obstruction. Few studies have investigated epigenetic mechanisms relating to EPS. Here we evaluated the therapeutic effects of DNA demethylation in experimental EPS. Experimental EPS was induced by intraperitoneal injection of 0.1% chlorhexidine gluconate (CG) and 15% ethanol in non-uremic male Sprague-Dawley (SD) rats. Rats were divided into three groups: group C (N=5) with saline injection only, group CG (N=7) with EPS induction for 4 weeks, and chlorhexidine gluconate and azacytidine (CGA) treated group (N=7) with EPS induction for 4 weeks and 5'-azacytidine injection for the last 2 weeks. Morphometric analysis of peritoneum and immunohistochemical staining for type 1 collagen and α-smooth muscle actin (α-SMA) were performed. Expressions of transforming growth factor-ß (TGF-ß), fibroblast-specific protein 1 (FSP1), and DNA methyltransferase 1 (DNMT1) were analyzed by Western blot. Methylation-specific polymerase chain reaction (PCR) for Ras GTPase activating-like protein 1 (RASAL1) was performed with measurement of RASAL1 protein expression. Parietal peritoneal thickness and the number of vessels in omental tissue were significantly decreased in group CGA compared to group CG, as were the expressions of type 1 collagen, α-SMA, TGF-ß, and FSP1. DNMT1 was significantly increased in group CG, and reduced in group CGA. RASAL1 hypermethylation was associated with decreased RASAL1 protein expression in group CG, which was reversed in group CGA. DNA demethylation by 5'-azacytidine treatment improved pathologic changes of the peritoneum in experimental EPS, and was associated with reversal of increased DNMT1 expression and RASAL1 hypermethylation.
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Azacitidina/farmacología , Metilación de ADN , Diálisis Peritoneal/efectos adversos , Fibrosis Peritoneal/fisiopatología , Animales , Clorhexidina/análogos & derivados , Clorhexidina/toxicidad , ADN (Citosina-5-)-Metiltransferasa 1 , ADN (Citosina-5-)-Metiltransferasas/genética , Modelos Animales de Enfermedad , Etanol/toxicidad , Regulación de la Expresión Génica , Masculino , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/genética , Ratas , Ratas Sprague-Dawley , Proteínas Activadoras de ras GTPasa/genéticaAsunto(s)
Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Diálisis Peritoneal , Fibrosis Peritoneal/prevención & control , Espironolactona/uso terapéutico , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fibrosis Peritoneal/patología , Fibrosis Peritoneal/fisiopatología , Sistema Renina-Angiotensina/efectos de los fármacosRESUMEN
INTRODUCTION: Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD). Over the past decade in Japan, a multidisciplinary approach has been adopted to minimize the incidence and improve outcomes of EPS. This strategy includes planned PD discontinuation for high-risk patients and the introduction of biocompatible solutions. This study examined the current clinical status of EPS in representative PD centers in Japan. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Patients (n = 1,338) from 55 PD centers in Japan who were using neutral-pH solutions from the initiation of therapy (mean age, 62 years; median PD duration, 32 months; concomitant use of icodextrin, 35.2%; PD and hemodialysis combination therapy, 12.2%) were assessed every 6 months to ascertain the reasons for PD discontinuation and the development of EPS development. Outcomes were also recorded. The study period was from November 2008 to March 2012. RESULTS: There were 727 patients who discontinued PD, including 163 deaths. Among all causes of PD withdrawal except for death, planned PD discontinuation to avoid EPS was utilized in 58 cases (7.1% in total). The strategy was increasingly utilized in proportion to the duration of PD: 0.5% for patients undergoing PD for < 3 years, 0.6% for patients undergoing PD for 5 years, 14.7% for patients undergoing PD for 8 years, and 35.5% for patients undergoing PD for > 8 years. Fourteen patients developed EPS (three cases after PD), which corresponded with an overall incidence of 1.0%. The incidence according to the duration of PD was 0.3% for PD < 3 years, 0.6% for PD = 5 years, 2.3% for PD = 8 years, and 1.2% for PD > 8 years. In terms of therapy, 11 patients were treated with prednisolone (PSL), and surgical enterolysis was utilized in two cases. Complete remission of abdominal symptoms was achieved in twelve patients (85.7%), and three died due to EPS (mortality rate of 21.4%). CONCLUSIONS: Use of the multidisciplinary approach described above reduces the risk of the development of EPS according to PD duration. In cases of de novo EPS cases in Japan, this strategy can also attenuate the clinical course of the condition.