¿Es útil el SPPB como método de screening de capacidad funcional en pacientes con enfermedad renal crónica avanzada? / Is SPPB useful as a screening method of functional capacity in patients with advanced chronic kidney disease?

INTRODUCCIÓN Y OBJETIVO: Una de las consecuencias de la ERC, es el deterioro de la capacidad funcional, pudiéndose manifestar desde distintos estadios de la enfermedad, hasta el tratamiento renal sustitutivo. El objetivo de este estudio fue determinar la funcionalidad de los pacientes con ERCA, mediante test de capacidad funcional, valorando de forma paralela la utilidad del SPPB como test de cribado. Materiales y métodos: Se evaluó la capacidad funcional de pacientes ERCA, utilizando los test SPPB, 6MM, TUTG y STS. También se determinó la fuerza muscular con dinamometría manual. Resultados: De 121 pacientes que acudieron a la consulta ERCA, 118 presentaron una mínima funcionalidad para poder realizar pruebas de capacidad funcional, un 71,2% de los pacientes fueron capaces de realizar los 4 test, un 28,8% solo pudo realizar el test SPPB. A un 71,43% de pacientes que presentaron una puntuación baja en SPPB, no se les pudo seguir evaluando con el resto de test, mientras que el 92,31% de los que presentaron una puntuación alta, continuaron con el resto de pruebas. Al diferenciar por rangos de edad, la mayoría de los pacientes jóvenes presentaban mínimas limitaciones, encontrando tasas más altas de discapacidad en rangos de edad mayores. Una buena puntuación en SPPB supuso presentar buena capacidad funcional y permitió seguir evaluando al paciente, obteniendo mejores resultados con el resto de test y más fuerza muscular. Una buena composición corporal y mejor estado nutricional supuso una mejor funcionalidad. Conclusión: A falta de un consenso de cuál es el mejor método de determinar la capacidad funcional del paciente renal, y para poder evaluar a todos los pacientes, proponemos utilizar el test SPPB como método de screening, y en función del resultado utilizar el resto de los test para realizar estudio más completo si es necesario

INTRODUCTION AND OBJECTIVE: One of the consequences of the CKD, is the deterioration of the functional capacity, being able to manifest from different stages of the disease, until renal replacement therapy. The objective of this study was to determine the functionality of patients with CKD through functional capacity test, valuing the usefulness of the SPPB as a screening test in parallel. Materials and methods: It assessed the functional capacity of patients with CKD, using the test SPPB, 6MM, TUTG and STS. Also found the muscle strength with manual dynamometry. RESULTS: Of 121 patients who came to the CKD query, 118 presented a minimum functionality to perform tests of functional capacity, a 71.2% of the patients were able to perform 4 tests, a 28.8% only could make the SPPB test. To a 71.43% of patients who presented a low score in SPPB, not could follow assessed them with the rest of the test, while the 92.31% of which had a high score, continued with the rest of the evidence. To differentiate by age ranges, the majority of young patients have minimal limitations, finding higher rates of disability in older age ranges. A good score in SPPB meant to present good functional capacity and allowed to continue evaluating the patient, obtaining better results with the rest of test and more muscle strength. A good nutritional better status and body composition was a better functionality. CONCLUSION: In the absence of a consensus of what is the best method of determining the functional capacity of the kidney patient, and to assess all patients, propose to use the test SPPB as screening method, and depending on the result used as the rest of the test to more complete if it is necessary to study

Natural Plants Compounds as Modulators of Epithelial-to-Mesenchymal Transition.

Epithelial-to-mesenchymal transition (EMT) is a self-regulated physiological process required for tissue repair that, in non-controled conditions may lead to fibrosis, angiogenesis, loss of normal organ function or cancer. Although several molecular pathways involved in EMT regulation have been described, this process does not have any specific treatment. This article introduces a systematic review of effective natural plant compounds and their extract that modulates the pathological EMT or its deleterious effects, through acting on different cellular signal transduction pathways both in vivo and in vitro. Thereby, cryptotanshinone, resveratrol, oxymatrine, ligustrazine, osthole, codonolactone, betanin, tannic acid, gentiopicroside, curcumin, genistein, paeoniflorin, gambogic acid and Cinnamomum cassia extracts inhibit EMT acting on transforming growth factor-ß (TGF-ß)/Smads signaling pathways. Gedunin, carnosol, celastrol, black rice anthocyanins, Duchesnea indica, cordycepin and Celastrus orbiculatus extract downregulate vimectin, fibronectin and N-cadherin. Sulforaphane, luteolin, celastrol, curcumin, arctigenin inhibit ß-catenin signaling pathways. Salvianolic acid-A and plumbagin block oxidative stress, while honokiol, gallic acid, piperlongumine, brusatol and paeoniflorin inhibit EMT transcription factors such as SNAIL, TWIST and ZEB. Plectranthoic acid, resveratrol, genistein, baicalin, polyphyllin I, cairicoside E, luteolin, berberine, nimbolide, curcumin, withaferin-A, jatrophone, ginsenoside-Rb1, honokiol, parthenolide, phoyunnanin-E, epicatechin-3-gallate, gigantol, eupatolide, baicalin and baicalein and nitidine chloride inhibit EMT acting on other signaling pathways (SIRT1, p38 MAPK, NFAT1, SMAD, IL-6, STAT3, AQP5, notch 1, PI3K/Akt, Wnt/ß-catenin, NF-κB, FAK/AKT, Hh). Despite the huge amount of preclinical data regarding EMT modulation by the natural compounds of plant, clinical translation is poor. Additionally, this review highlights some relevant examples of clinical trials using natural plant compounds to modulate EMT and its deleterious effects. Overall, this opens up new therapeutic alternatives in cancer, inflammatory and fibrosing diseases through the control of EMT process.

Is SPPB useful as a screening method of functional capacity in patients with advanced chronic kidney disease? / ¿Es útil el SPPB como método de screening de capacidad funcional en pacientes con enfermedad renal crónica avanzada?

INTRODUCTION AND OBJECTIVE: One of the consequences of the CKD, is the deterioration of the functional capacity, being able to manifest from different stages of the disease, until renal replacement therapy. The objective of this study was to determine the functionality of patients with CKD through functional capacity test, valuing the usefulness of the SPPB as a screening test in parallel. MATERIALS AND METHODS: It assessed the functional capacity of patients with CKD, using the test SPPB, 6MM, TUTG and STS. Also found the muscle strength with manual dynamometry. RESULTS: Of 121 patients who came to the CKD query, 118 presented a minimum functionality to perform tests of functional capacity, a 71.2% of the patients were able to perform 4 tests, a 28.8% only could make the SPPB test. To a 71.43% of patients who presented a low score in SPPB, not could follow assessed them with the rest of the test, while the 92.31% of which had a high score, continued with the rest of the evidence. To differentiate by age ranges, the majority of young patients have minimal limitations, finding higher rates of disability in older age ranges. A good score in SPPB meant to present good functional capacity and allowed to continue evaluating the patient, obtaining better results with the rest of test and more muscle strength. A good nutritional better status and body composition was a better functionality. CONCLUSION: In the absence of a consensus of what is the best method of determining the functional capacity of the kidney patient, and to assess all patients, propose to use the test SPPB as screening method, and depending on the result used as the rest of the test to more complete if it is necessary to study.

Influence of dietary protein intake on body composition in chronic kidney disease patients in stages 3-5: A cross-sectional study / Influencia del consumo de proteínas en la composición corporal de pacientes con enfermedad renal crónica en estadios 3-5: estudio transversal

INTRODUCTION: A controlled protein intake has shown beneficial effects to preserve renal function and nutritional status in chronic kidney disease (CKD) patients. This study aimed to analyze usual dietary protein intake and its potential contribution to body composition in CKD patients in stages 3-5. METHOD: Cross-sectional study in 134 CKD patients in stages 3-5 (mean e-GFR: 19.4 ± 8.7 ml/min/1.73 m2; males 68.7% and primary CKD etiology was diabetes mellitus, 35.8%). Demographic, clinical and nutritional parameters were evaluated. Normalized protein nitrogen appearance (nPNA), was used as a surrogate marker of dietary protein intake. The sample was classified into three nPNA groups (Gn): G1: < 0.8g/kg/day; G2: 0.8-1g/kg/day and, G3: ≥ 1g/kg/day. Assessment of nutritional status using the malnutrition-inflammation score (MIS), anthropometric measures and laboratory parameters. Analysis of body composition and hydration status by bioelectrical impedance analysis (BIVA-101-RJL system). Statistical analysis by SPSS V.20. RESULTS: Overall mean nPNA values were 0.91 ± 0.23 g of protein/kg BW/day and only 32.1% had a dietary protein intake < 0.8g of protein/kg BW/day. Most of the CKD patients (65.5%) were in stages 4 or 5. Prevalence of protein-energy-wasting (PEW) syndrome measured by MIS was 15%. By analyzing differences between nPNA groups, body weight (BW), BMI and triceps-skinfold (TSF) thickness were significantly higher in the group with nPNA ≥ 1g/kg BW/day (G3), whereas a significant inverse relationship was found with the percentages of body cell mass (BCM%), fat-free mass (FFM%), muscle mass (MM%) and phase angle (PA) in the group with the lowest nPNA (G1). Analysis of gender among subjects showed significant differences with BW, FFM%, TSF and mid-arm muscle circumference (MAMC%). Linear regression analysis showed that resistance, BCM%, MM%, and serum albumin were significant predictors of nPNA as a surrogate marker of daily protein intake (R = 0.51; R2 = 0.29; R2 adjusted = 0.23; p < 0.001). CONCLUSION: Controlled protein intake is one of the cornerstones of treatment in CKD patients. A low protein intake in patients with CKD stages 3 and 4-5 was associated with loss of muscle mass in the advanced-CKD unit. The loss of muscle mass appears as an early indicator of nutritional comprised. Factors such, elderly age and loss of eGFR, showed lower protein intake and were associated with muscle loss, especially in women. Further longitudinal studies are required to evaluate the contribution of different protein intakes to uremic symptoms, nutritional status, body composition and CKD progression

INTRODUCCIÓN: El control de la ingesta proteica ha mostrado efectos beneficiosos preservando la función renal y el estado nutricional en pacientes con enfermedad renal crónica (ERC). El objetivo del estudio fue analizar la ingesta habitual de proteína, y su potencial contribución en la composición corporal en los pacientes con ERC estadios 3-5. MÉTODO: Estudio observacional transversal en 134 pacientes con ERC estadios 3-5 (media e-TFG: 19,4 ± 8,7ml/min/1,73 m2; varones: 68,7% y etiología primaria de la ERC, diabetes mellitus: 35,8%). Se evaluaron parámetros demográficos, clínicos y nutricionales. La aparición de nitrógeno proteico normalizado (nPNA) se utilizó como marcador sustituto de la ingesta proteica. La muestra fue clasificada según el nPNA en 3 grupos (Gn): G1: < 0,8g/kg/día; G2: 0,8-1g/kg/día y G3: ≥ 1g/kg/día. Valoración nutricional por la escala de malnutrición-inflamación (MIS), medidas antropométricas y parámetros de laboratorio. Análisis de composición corporal y del patrón de hidratación mediante bioimpedancia eléctrica (BIVA-101®, RJL System). Análisis estadístico por SPSS(R) V.20. RESULTADOS: Globalmente los valores medios de nPNA fueron 0,91 ± 0,23g proteína/kg peso corporal/día, y tan solo el 32,1% tenían una ingesta proteica < 0,8 g de proteína/kg peso corporal/día. El 65,5% de los pacientes con ERC estaban en estadios 4 y 5. La prevalencia de síndrome de desgaste proteico-energético (SDP) medido por MIS era del 15%. Analizando las diferencias con el nPNA entre los grupos, el peso corporal, el índice de masa corporal y el pliegue tricipital (PCT), eran significativamente mayores en el grupo con nPNA≥1g/kg peso corporal/día (G3), mientras que se encontró relación inversa significativa con los porcentajes de la masa celular (MC%), de la masa magra (MMagra%), de la masa muscular (MM%) y del ángulo de fase (AF) en el grupo con menor nPNA (G1). El análisis del género entre los sujetos mostró diferencias significativas con el peso corporal, MMagra%, PCT y la circunferencia muscular del brazo (CMB%). El análisis de regresión lineal demostró que la resistencia MC%, MM% y la albúmina sérica eran predictores significativos del nPNA como marcador de la ingesta proteica habitual (R = 0,51; R2 = 0,29; R2 ajustado = 0,23; p < 0,001). CONCLUSIÓN: El control de la ingesta proteica es uno de los pilares del tratamiento en los pacientes con ERC. La dieta hipoproteica en pacientes con ERC estadios 3-5 se asoció con una pérdida de la masa muscular en la unidad de ERC avanzada. La pérdida de masa muscular aparece como un indicador temprano de compromiso nutricional. La edad avanzada y la pérdida de TFG-e se asociaron con menor ingesta proteica y pérdida de masa muscular asociada, especialmente en mujeres. Nuevos estudios longitudinales, son necesarios para evaluar la contribución de la ingesta de proteínas en los síntomas urémicos, el estado nutricional, la composición corporal y la progresión de la ERC

Influence of dietary protein intake on body composition in chronic kidney disease patients in stages 3-5: A cross-sectional study.

INTRODUCTION: A controlled protein intake has shown beneficial effects to preserve renal function and nutritional status in chronic kidney disease (CKD) patients. This study aimed to analyze usual dietary protein intake and its potential contribution to body composition in CKD patients in stages 3-5. METHOD: Cross-sectional study in 134 CKD patients in stages 3-5 (mean e-GFR: 19.4±8.7ml/min/1.73m2; males 68.7% and primary CKD etiology was diabetes mellitus, 35.8%). Demographic, clinical and nutritional parameters were evaluated. Normalized protein nitrogen appearance (nPNA), was used as a surrogate marker of dietary protein intake. The sample was classified into three nPNA groups (Gn): G1: <0.8g/kg/day; G2: 0.8-1g/kg/day and, G3: ≥1g/kg/day. Assessment of nutritional status using the malnutrition-inflammation score (MIS), anthropometric measures and laboratory parameters. Analysis of body composition and hydration status by bioelectrical impedance analysis (BIVA-101-RJL system). Statistical analysis by SPSS v.20. RESULTS: Overall mean nPNA values were 0.91±0.23g of protein/kg BW/day and only 32.1% had a dietary protein intake <0.8g of protein/kg BW/day. Most of the CKD patients (65.5%) were in stages 4 or 5. Prevalence of protein-energy-wasting (PEW) syndrome measured by MIS was 15%. By analyzing differences between nPNA groups, body weight (BW), BMI and triceps-skinfold (TSF) thickness were significantly higher in the group with nPNA ≥1g/kg BW/day (G3), whereas a significant inverse relationship was found with the percentages of body cell mass (BCM%), fat-free mass (FFM%), muscle mass (MM%) and phase angle (PA) in the group with the lowest nPNA (G1). Analysis of gender among subjects showed significant differences with BW, FFM%, TSF and mid-arm muscle circumference (MAMC%). Linear regression analysis showed that resistance, BCM%, MM%, and serum albumin were significant predictors of nPNA as a surrogate marker of daily protein intake (R=0.51; R2=0.29; R2 adjusted=0.23; p<0.001). CONCLUSION: Controlled protein intake is one of the cornerstones of treatment in CKD patients. A low protein intake in patients with CKD stages 3 and 4-5 was associated with loss of muscle mass in the advanced-CKD unit. The loss of muscle mass appears as an early indicator of nutritional comprised. Factors such, elderly age and loss of eGFR, showed lower protein intake and were associated with muscle loss, especially in women. Further longitudinal studies are required to evaluate the contribution of different protein intakes to uremic symptoms, nutritional status, body composition and CKD progression.

Amiloidosis derivada del factor quimiotáctico de leucocitos 2 (ALECT2): a propósito de un caso / LECT2-associated renal amyloidosis (ALECT2): A case report

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El triacetato de celulosa asimétrico es una alternativa segura y eficaz para la hemodiafiltración en línea / Asymmetric cellulose triacetate is a safe and effective alternative for online haemodiafiltration

ANTECEDENTES: En la hemodiafiltración posdilucional se han usado solo membranas sintéticas. Ahora contamos con un triacetato de celulosa asimétrico (ATA(R)) cuyas características lo hacen apto para esta técnica. OBJETIVOS: Describir las prestaciones y el comportamiento in vivo de esta membrana estudiando la eficacia depurativa y el uso clínico, además de su biocompatibilidad aguda tras un mes de tratamiento. MÉTODOS: Estudio prospectivo observacional en el que se incluyeron 23 pacientes que se dializaron durante 4 semanas con ATA(R) manteniendo su pauta previa. RESULTADOS: Se realizaron 287 sesiones y se recogieron 264 sesiones completas. Con un tiempo efectivo de 243,7 (17,6) min y un flujo medio de sangre de 371,7 (23) ml/min, se obtuvo un Kt medio de 56,3 (5,3) l, un volumen convectivo de 27,1 (4,2) l, con una fracción de filtración del 29,9 (3,7) %, un porcentaje de reducción (RR) de urea de 81 (5,2) %, un RR de creatinina de 74,7 (4,6) %, un RR de Beta2-microglobulina de 76,5 (4,8) % y un RR de proteína transportadora de retinol de 18,6 (7,6) %. No se produjeron problemas técnicos ni alarmas. No fue preciso cambiar la dosificación de heparina. A los 30 min de la sesión no se produjo ningún aumento de C3a, C5a ni leucopenia. Tampoco se modificaron de forma significativa las poblaciones monocitarias ni la IL-Beta1 ni IL-6 tras un mes de tratamiento. CONCLUSIONES: ATA(R) logra un Kt y un volumen convectivo adecuados, sin problemas técnicos y con buen perfil de biocompatibilidad e inflamatorio, lo que lo convierte en una posibilidad más de tratamiento para hemodiafiltración posdilucional, máxime en pacientes alérgicos a membranas sintéticas

BACKGROUND: In post-dilution haemodiafiltration only synthetic membranes have been used to date. Asymmetric cellulose triacetate (ATA(TM)) is now available, whose characteristics are suitable for this technique. OBJECTIVES: To describe the in vivo performance and behaviour of this membrane, to identify its depurative effectiveness, use in clinical practice and its biocompatibility, both acute and after one month of treatment. METHODS: Observational prospective study of 23 patients who were dialysed for 4 weeks using an ATA(TM) membrane and who maintained their prior regimen. RESULTS: A total of 287 sessions were performed and 264 complete sessions were collected. With an effective time of 243.7 (17.6) min and a mean blood flow of 371.7 (23) ml/min, an average Kt of 56.3 (5.3) l was observed, as well as a convection volume of 27.1 (4.2) l, a filtration fraction of 29.9 (3.7) %, a urea reduction ratio (RR) of 81 (5.2) %, a creatinine RR of 74.7 (4.6) %, a Beta2-microglobulin RR of 76.5 (4.8) % and a retinol binding protein RR of 18.6 (7.6) %. There were no technical problems or alarms. Changing the heparin dosage was not necessary. No increases in C3a or C5a concentrations or leukopenia were observed in the first 30min of the session. Neither the monocyte subpopulations nor IL-Beta1 or IL-6 were significantly altered after one month of treatment. CONCLUSIONS: The new ATA(TM) membrane achieves adequate Kt and convection volume, without technical problems and with good biocompatibility and inflammatory profiles. It is therefore a valid option for post-dilution haemodiafiltration, particularly in patients allergic to synthetic membranes

Asymmetric cellulose triacetate is a safe and effective alternative for online haemodiafiltration. / El triacetato de celulosa asimétrico es una alternativa segura y eficaz para la hemodiafiltración en línea.

BACKGROUND: In post-dilution haemodiafiltration only synthetic membranes have been used to date. Asymmetric cellulose triacetate (ATA™) is now available, whose characteristics are suitable for this technique. OBJECTIVES: To describe the in vivo performance and behaviour of this membrane, to identify its depurative effectiveness, use in clinical practice and its biocompatibility, both acute and after one month of treatment. METHODS: Observational prospective study of 23 patients who were dialysed for 4 weeks using an ATA™ membrane and who maintained their prior regimen. RESULTS: A total of 287 sessions were performed and 264 complete sessions were collected. With an effective time of 243.7 (17.6) min and a mean blood flow of 371.7 (23) ml/min, an average Kt of 56.3 (5.3) l was observed, as well as a convection volume of 27.1 (4.2) l, a filtration fraction of 29.9 (3.7) %, a urea reduction ratio (RR) of 81 (5.2) %, a creatinine RR of 74.7 (4.6) %, a ß2-microglobulin RR of 76.5 (4.8) % and a retinol binding protein RR of 18.6 (7.6) %. There were no technical problems or alarms. Changing the heparin dosage was not necessary. No increases in C3a or C5a concentrations or leukopenia were observed in the first 30min of the session. Neither the monocyte subpopulations nor IL-ß1 or IL-6 were significantly altered after one month of treatment. CONCLUSIONS: The new ATA™ membrane achieves adequate Kt and convection volume, without technical problems and with good biocompatibility and inflammatory profiles. It is therefore a valid option for post-dilution haemodiafiltration, particularly in patients allergic to synthetic membranes.

Corrigendum to "T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage".

[This corrects the article DOI: 10.1155/2015/416480.].

Genomic reprograming analysis of the Mesothelial to Mesenchymal Transition identifies biomarkers in peritoneal dialysis patients.

Peritoneal dialysis (PD) is an effective renal replacement therapy, but a significant proportion of patients suffer PD-related complications, which limit the treatment duration. Mesothelial-to-mesenchymal transition (MMT) contributes to the PD-related peritoneal dysfunction. We analyzed the genetic reprograming of MMT to identify new biomarkers that may be tested in PD-patients. Microarray analysis revealed a partial overlapping between MMT induced in vitro and ex vivo in effluent-derived mesothelial cells, and that MMT is mainly a repression process being higher the number of genes that are down-regulated than those that are induced. Cellular morphology and number of altered genes showed that MMT ex vivo could be subdivided into two stages: early/epithelioid and advanced/non-epithelioid. RT-PCR array analysis demonstrated that a number of genes differentially expressed in effluent-derived non-epithelioid cells also showed significant differential expression when comparing standard versus low-GDP PD fluids. Thrombospondin-1 (TSP1), collagen-13 (COL13), vascular endothelial growth factor A (VEGFA), and gremlin-1 (GREM1) were measured in PD effluents, and except GREM1, showed significant differences between early and advanced stages of MMT, and their expression was associated with a high peritoneal transport status. The results establish a proof of concept about the feasibility of measuring MMT-associated secreted protein levels as potential biomarkers in PD.

Enfermedad óseo mineral relacionada con la enfermedad renal crónica: Klotho y FGF23; implicaciones cardiovasculares / Bone mineral disorder in chronic kidney disease: Klotho and FGF23; cardiovascular implications

Una de las principales causas de morbimortalidad en el paciente con enfermedad renal crónica es la cardiovascular. La inflamación y las alteraciones en el metabolismo óseo mineral son una condición patológica que conlleva aumento del riesgo cardiovascular en la enfermedad renal crónica. Los parámetros bioquímicos clásicos del metabolismo óseo mineral como fósforo, calcio, vitamina D y PTH tienen una implicación muy conocida en el riesgo cardiovascular. Los nuevos marcadores, FGF23 y klotho, también podrían estar implicados en la enfermedad cardiovascular (AU)

Cardiovascular factors are one of the main causes of morbidity and mortality in patients with chronic kidney disease. Bone mineral metabolism disorders and inflammation are pathological conditions that involve increased cardiovascular risk in chronic kidney disease. The cardiovascular risk involvement of bone mineral metabolism classical biochemical parameters such as phosphorus, calcium, vitamin D and PTH is well known. The newest markers, FGF23 and klotho, could also be implicated in cardiovascular disease (AU)

Bone mineral disorder in chronic kidney disease: Klotho and FGF23; cardiovascular implications. / Enfermedad óseo mineral relacionada con la enfermedad renal crónica: Klotho y FGF23; implicaciones cardiovasculares.

Cardiovascular factors are one of the main causes of morbidity and mortality in patients with chronic kidney disease. Bone mineral metabolism disorders and inflammation are pathological conditions that involve increased cardiovascular risk in chronic kidney disease. The cardiovascular risk involvement of bone mineral metabolism classical biochemical parameters such as phosphorus, calcium, vitamin D and PTH is well known. The newest markers, FGF23 and klotho, could also be implicated in cardiovascular disease.

Biocompatible Dialysis Solutions Preserve Peritoneal Mesothelial Cell and Vessel Wall Integrity. A Case-Control Study on Human Biopsies.

UNLABELLED: ♦ INTRODUCTION: Chronic exposure to conventional peritoneal dialysis (PD) solutions has been related to peritoneal function alterations in PD patients, and associated with mesothelial cell loss, submesothelial fibrosis, vasculopathy, and angiogenesis. In vitro and ex vivo analyses, as well as studies with animal models, have demonstrated that biocompatible PD solutions attenuate these morphological alterations. Our aim was to confirm the morphological benefits of biocompatible solutions in PD patients. ♦ METHODS: We analyzed biopsies from 23 patients treated with biocompatible solutions (study group, SG), and compared them with a control group (n = 23) treated with conventional solutions (CG), matched for time on PD. ♦ RESULTS: A total of 56.5% of SG patients showed total or partial preservation of mesothelial cells monolayer, in contrast with 26.1% of patients in CG (p = 0.036). Peritoneal fibrosis was not significantly less frequent in SG patients (47.8% SG vs 69.6% CG; p = 0.13). In patients without previous peritonitis, a significantly lower prevalence of fibrosis was present in SG patients (41.7% SG vs 77.8% CG; p = 0.04). Hyalinizing vasculopathy (HV) was significantly lower in SG (4.3% SG vs 30.4% CG; p = 0.02). Cytokeratin-positive fibroblast-like cells were detected in 10 patients (22%), but the prevalence was not significantly lower in SG. In the univariate regression analysis, the use of biocompatible solutions was associated with mesothelial monolayer integrity (p = 0.04) and an absence of vasculopathy (p = 0.04). ♦ CONCLUSION: The present study demonstrates in vivo in human biopsies that biocompatible solutions are better tolerated by the peritoneum in the medium and long term than conventional solutions.

Rapamycin Protects from Type-I Peritoneal Membrane Failure Inhibiting the Angiogenesis, Lymphangiogenesis, and Endo-MT.

Preservation of peritoneal membrane (PM) is essential for long-term survival in peritoneal dialysis (PD). Continuous presence of PD fluids (PDF) in the peritoneal cavity generates chronic inflammation and promotes changes of the PM, such as fibrosis, angiogenesis, and lymphangiogenesis. Mesothelial-to-mesenchymal transition (MMT) and endothelial-to-mesenchymal transition (Endo-MT) seem to play a central role in this pathogenesis. We speculated that Rapamycin, a potent immunosuppressor, could be beneficial by regulating blood and lymphatic vessels proliferation. We demonstrate that mice undergoing a combined PD and Rapamycin treatment (PDF + Rapa group) presented a reduced PM thickness and lower number of submesothelial blood and lymphatic vessels, as well as decreased MMT and Endo-MT, comparing with their counterparts exposed to PD alone (PDF group). Peritoneal water transport in the PDF + Rapa group remained at control level, whereas PD effluent levels of VEGF, TGF-ß, and TNF-α were lower than in the PDF group. Moreover, the treatment of mesothelial cells with Rapamycin in vitro significantly decreased VEGF synthesis and selectively inhibited the VEGF-C and VEGF-D release when compared with control cells. Thus, Rapamycin has a protective effect on PM in PD through an antifibrotic and antiproliferative effect on blood and lymphatic vessels. Moreover, it inhibits Endo-MT and, at least partially, MMT.

T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage.

Fibrosis is a general complication in many diseases. It is the main complication during peritoneal dialysis (PD) treatment, a therapy for renal failure disease. Local inflammation and mesothelial to mesenchymal transition (MMT) are well known key phenomena in peritoneal damage during PD. New data suggest that, in the peritoneal cavity, inflammatory changes may be regulated at least in part by a delicate balance between T helper 17 and regulatory T cells. This paper briefly reviews the implication of the Th17/Treg-axis in fibrotic diseases. Moreover, it compares current evidences described in PD animal experimental models, indicating a loss of Th17/Treg balance (Th17 predominance) leading to peritoneal damage during PD. In addition, considering the new clinical and animal experimental data, new therapeutic strategies to reduce the Th17 response and increase the regulatory T response are proposed. Thus, future goals should be to develop new clinical biomarkers to reverse this immune misbalance and reduce peritoneal fibrosis in PD.

Arritmia cardiaca grave por hipopotasemia. Influencia de las sustancias diuréticas / Severe arrhythmia due to hypokalemia. Influence from diuretic substances

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Amelioration of ischemic brain damage by peritoneal dialysis.

Ischemic stroke is a devastating condition, for which there is still no effective therapy. Acute ischemic stroke is associated with high concentrations of glutamate in the blood and interstitial brain fluid. The inability of the tissue to retain glutamate within the cells of the brain ultimately provokes neuronal death. Increased concentrations of interstitial glutamate exert further excitotoxic effects on healthy tissue surrounding the infarct zone. We developed a strategy based on peritoneal dialysis to reduce blood glutamate levels, thereby accelerating brain-to-blood glutamate clearance. In a rat model of stroke, this simple procedure reduced the transient increase in glutamate, consequently decreasing the size of the infarct area. Functional magnetic resonance imaging demonstrated that the rescued brain tissue remained functional. Moreover, in patients with kidney failure, peritoneal dialysis significantly decreased glutamate concentrations. Our results suggest that peritoneal dialysis may represent a simple and effective intervention for human stroke patients.

Tamoxifen ameliorates peritoneal membrane damage by blocking mesothelial to mesenchymal transition in peritoneal dialysis.

Mesothelial-to-mesenchymal transition (MMT) is an auto-regulated physiological process of tissue repair that in uncontrolled conditions such as peritoneal dialysis (PD) can lead to peritoneal fibrosis. The maximum expression of peritoneal fibrosis induced by PD fluids and other peritoneal processes is the encapsulating peritoneal sclerosis (EPS) for which no specific treatment exists. Tamoxifen, a synthetic estrogen, has successfully been used to treat retroperitoneal fibrosis and EPS associated with PD. Hence, we used in vitro and animal model approaches to evaluate the efficacy of Tamoxifen to inhibit the MMT as a trigger of peritoneal fibrosis. In vitro studies were carried out using omentum-derived mesothelial cells (MCs) and effluent-derived MCs. Tamoxifen blocked the MMT induced by transforming growth factor (TGF)-ß1, as it preserved the expression of E-cadherin and reduced the expression of mesenchymal-associated molecules such as snail, fibronectin, collagen-I, α-smooth muscle actin, and matrix metalloproteinse-2. Tamoxifen-treatment preserved the fibrinolytic capacity of MCs treated with TGF-ß1 and decreased their migration capacity. Tamoxifen did not reverse the MMT of non-epitheliod MCs from effluents, but it reduced the expression of some mesenchymal molecules. In mice PD model, we demonstrated that MMT progressed in parallel with peritoneal membrane thickness. In addition, we observed that Tamoxifen significantly reduced peritoneal thickness, angiogenesis, invasion of the compact zone by mesenchymal MCs and improved peritoneal function. Tamoxifen also reduced the effluent levels of vascular endothelial growth factor and leptin. These results demonstrate that Tamoxifen is a therapeutic option to treat peritoneal fibrosis, and that its protective effect is mediated via modulation of the MMT process.