2 research outputs found
Impacto de la inflamaci贸n y fibrosis en la funci贸n del injerto renal
No full textA pesar de los grandes avances en el campo del trasplante renal (TR), los resultados a largo plazo a煤n no son 贸ptimos. Varios estudios han demostrado que diversos factores como la inflamaci贸n precoz y/o la presencia de fibrosis intersticial (FI) est谩n asociados a un peor pron贸stico del injerto, pero todav铆a se trata de un tema controvertido. En este estudio analizamos el estado inflamatorio (Banff, macr贸fagos CD68+, fenotipos de macr贸fagos M1-M2) y la expresi贸n g茅nica de m煤ltiples factores relacionados con la inflamaci贸n y FI (TGF-尾1, metaloproteinasas, prote铆nas de matriz extracelular, entre otros) en injertos procedentes de donantes cad谩ver (DC) y los comparamos con un grupo control de donantes vivos (DV). As铆 mismo analizamos la potencial asociaci贸n de estos factores, ya desde antes de la implantaci贸n, con diversas variables cl铆nicas y con la funci贸n renal a medio-largo plazo. Entre otros hallazgos, confirmamos que los 贸rganos procedentes de DC presentan un mayor infiltrado intersticial de macr贸fagos CD68+ y describimos que tanto la expresi贸n g茅nica de varias prote铆nas pro-inflamatorias como pro-fibr贸ticas se encuentran significativamente incrementadas en los DC incluso antes de la implantaci贸n. Tambi茅n observamos un aumento en la expresi贸n g茅nica de prote铆nas que promueven la infiltraci贸n leucocitaria, especialmente macr贸fagos, en el tejido (MCP-1, ICAM-1), as铆 como de mediadores de inflamaci贸n como TNF伪, IL1尾. Tambi茅n se observ贸 un aumento en la expresi贸n g茅nica de receptores de membrana de los macr贸fagos que les confiere el fenotipo inflamatorio (M1) as铆 como el antinflamatorio (M2). En los DC tambi茅n se observ贸 un aumento significativo de los precursores y mediadores de FI. Es de destacar que muchos de estos par谩metros (inflamatorios y pro-fibr贸ticos) se asociaron a la funci贸n renal estimada (MDRD) en distintos tiempos de seguimiento. El an谩lisis multivariante (regresi贸n lineal m煤ltiple) mostr贸 que tanto la funci贸n retrasada del injerto como la expresi贸n g茅nica de TGF-尾1 a los cuatro meses fueron predictores independientes de la funci贸n del injerto del 煤ltimo control (media 5.8 1.0 a帽os). En conclusi贸n, confirmamos la estrecha interconexi贸n entre inflamaci贸n y fibrosis especialmente en el TR de DC, que 茅sta se inicia ya antes de la implantaci贸n y persiste post-TR y que estos factores muy precoces (potencialmente tratables) pueden determinar el pron贸stico del injerto a largo plazo.Despite great achievements in the field of renal transplantation (RT), long-term results are still not optimal. Several studies have shown that various factors such as early inflammation and/or the presence of interstitial fibrosis (IF) are associated with a worse graft prognosis, but this issue is still controversial and far from being resolved. In this study, we analyzed the inflammatory state (Banff, CD68 + macrophages, M1-M2 phenotypes, among others) and the gene expression of multiple factors related to both inflammation and IF (TGF-尾1, metalloproteinases, extracellular matrix proteins, among others) in grafts from cadaveric donors (CD) and they were compared with a control group from living donors (LD). We also analyzed the potential association of all these factors with several clinical variables with medium and/or long-term renal function. Among other findings, we confirm that organs from CD have a greater CD68+ macrophage infiltration and we describe that the expression of several proinflammatory and and profibrotic molecules is significantly increased in CD even before grafting. We also observed an increased gene expression of proteins related to graft leukocyte infiltration, mainly macrophages, such as MCP-1 or ICAM-1, as well as of inflammatory mediators such as TNF伪 or IL1尾. We also observed an increased gene expression of macrophage membrane cell receptors related to their inflammatory (M1) or anti-inflammatory (M2) phenotype. Finally, we described a significant increase of IF precursors and mediators in CD. It is noteworthy that multiple parameters (both inflammatory and profibrotic) were associated with the estimated glomerular filtration rate (MDRD) at different times. Multiple regression analysis revealed that delayed renal function as well as graft TGF-尾1 gene expression four months after RT were independent predictors of the last renal function control during follow-up (5.8 1.0 years). In conclusion, we confirm the existence of an especially close interconnection between inflammation and fibrosis, especially in the CD RT setting, starting before engraftment and progressing after RT, and that these very early (potentially treatable) factors may already devise its long-term graft prognosis
Impacto de la inflamaci贸n y fibrosis en la funci贸n del injerto renal
Get PDFA pesar de los grandes avances en el campo del trasplante renal (TR), los resultados a largo plazo a煤n no son 贸ptimos. Varios estudios han demostrado que diversos factores como la inflamaci贸n precoz y/o la presencia de fibrosis intersticial (FI) est谩n asociados a un peor pron贸stico del injerto, pero todav铆a se trata de un tema controvertido. En este estudio analizamos el estado inflamatorio (Banff, macr贸fagos CD68+, fenotipos de macr贸fagos M1-M2) y la expresi贸n g茅nica de m煤ltiples factores relacionados con la inflamaci贸n y FI (TGF-尾1, metaloproteinasas, prote铆nas de matriz extracelular, entre otros) en injertos procedentes de donantes cad谩ver (DC) y los comparamos con un grupo control de donantes vivos (DV). As铆 mismo analizamos la potencial asociaci贸n de estos factores, ya desde antes de la implantaci贸n, con diversas variables cl铆nicas y con la funci贸n renal a medio-largo plazo. Entre otros hallazgos, confirmamos que los 贸rganos procedentes de DC presentan un mayor infiltrado intersticial de macr贸fagos CD68+ y describimos que tanto la expresi贸n g茅nica de varias prote铆nas pro-inflamatorias como pro-fibr贸ticas se encuentran significativamente incrementadas en los DC incluso antes de la implantaci贸n. Tambi茅n observamos un aumento en la expresi贸n g茅nica de prote铆nas que promueven la infiltraci贸n leucocitaria, especialmente macr贸fagos, en el tejido (MCP-1, ICAM-1), as铆 como de mediadores de inflamaci贸n como TNF伪, IL1尾. Tambi茅n se observ贸 un aumento en la expresi贸n g茅nica de receptores de membrana de los macr贸fagos que les confiere el fenotipo inflamatorio (M1) as铆 como el antinflamatorio (M2). En los DC tambi茅n se observ贸 un aumento significativo de los precursores y mediadores de FI. Es de destacar que muchos de estos par谩metros (inflamatorios y pro-fibr贸ticos) se asociaron a la funci贸n renal estimada (MDRD) en distintos tiempos de seguimiento. El an谩lisis multivariante (regresi贸n lineal m煤ltiple) mostr贸 que tanto la funci贸n retrasada del injerto como la expresi贸n g茅nica de TGF-尾1 a los cuatro meses fueron predictores independientes de la funci贸n del injerto del 煤ltimo control (media 5.8 1.0 a帽os). En conclusi贸n, confirmamos la estrecha interconexi贸n entre inflamaci贸n y fibrosis especialmente en el TR de DC, que 茅sta se inicia ya antes de la implantaci贸n y persiste post-TR y que estos factores muy precoces (potencialmente tratables) pueden determinar el pron贸stico del injerto a largo plazo.Despite great achievements in the field of renal transplantation (RT), long-term results are still not optimal. Several studies have shown that various factors such as early inflammation and/or the presence of interstitial fibrosis (IF) are associated with a worse graft prognosis, but this issue is still controversial and far from being resolved. In this study, we analyzed the inflammatory state (Banff, CD68 + macrophages, M1-M2 phenotypes, among others) and the gene expression of multiple factors related to both inflammation and IF (TGF-尾1, metalloproteinases, extracellular matrix proteins, among others) in grafts from cadaveric donors (CD) and they were compared with a control group from living donors (LD). We also analyzed the potential association of all these factors with several clinical variables with medium and/or long-term renal function. Among other findings, we confirm that organs from CD have a greater CD68+ macrophage infiltration and we describe that the expression of several proinflammatory and and profibrotic molecules is significantly increased in CD even before grafting. We also observed an increased gene expression of proteins related to graft leukocyte infiltration, mainly macrophages, such as MCP-1 or ICAM-1, as well as of inflammatory mediators such as TNF伪 or IL1尾. We also observed an increased gene expression of macrophage membrane cell receptors related to their inflammatory (M1) or anti-inflammatory (M2) phenotype. Finally, we described a significant increase of IF precursors and mediators in CD. It is noteworthy that multiple parameters (both inflammatory and profibrotic) were associated with the estimated glomerular filtration rate (MDRD) at different times. Multiple regression analysis revealed that delayed renal function as well as graft TGF-尾1 gene expression four months after RT were independent predictors of the last renal function control during follow-up (5.8 1.0 years). In conclusion, we confirm the existence of an especially close interconnection between inflammation and fibrosis, especially in the CD RT setting, starting before engraftment and progressing after RT, and that these very early (potentially treatable) factors may already devise its long-term graft prognosis
