ABSTRACT
PURPOSE: The interaction of Shiga toxin (Stx) and/or lipopolysaccharide (LPS) with monocytes (Mo) may be central to the pathogenesis of hemolytic uremic syndrome (HUS), providing the cytokines necessary to sensitize endothelial cells to Stx action. We have previously demonstrated phenotypical alterations in Mo from HUS patients, including increased number of CD16+ Mo. Our aim was to investigate cytokine production in Mo from HUS patients. METHODS: We evaluated TNF-α and IL-10 intracellular contents and secretion in the different Mo subsets in mild (HUS 1) and moderate/severe (HUS 2 + 3) patients. As controls, we studied healthy (HC) and infected children (IC). We also studied Mo responsive capacity towards LPS, measuring the modulation of Mo surface molecules and cytokine production. RESULTS: In basal conditions, the intracellular measurement of TNF-α and IL-10 revealed that the highest number of cytokine-producing Mo was found in HUS 2 + 3 and IC, whereas LPS caused a similar increase in TNF-α and IL-10-producing Mo for all groups. However, when evaluating the release of TNF-α and IL-10, we found a diminished secretion capacity in the entire HUS group and IC compared to HC in basal and LPS conditions. Similarly, a lower Mo response to LPS in HUS 2 + 3 and IC groups was observed when surface markers were studied. CONCLUSION: These results indicate that Mo from severe cases of HUS, similar to IC but different to mild HUS cases, present functional changes in Mo subpopulations and abnormal responses to LPS.
Subject(s)
Hemolytic-Uremic Syndrome/immunology , Interleukin-10/immunology , Monocytes/immunology , Tumor Necrosis Factor-alpha/immunology , Child , Child, Preschool , Female , Humans , Infant , Interleukin-10/blood , Lipopolysaccharides/immunology , Male , Tumor Necrosis Factor-alpha/bloodABSTRACT
OBJECTIVE: The multicentric study of chronic renal failure, dialysis and transplant started in 1996 by the Nephrology Committee of the Argentine Pediatrics Society with the aim of knowing the development characteristics of children with this pathology. POPULATION, MATERIAL AND METHODS: The study included children and adolescents on conservative treatment, dialysis or transplant who have registered any of the three modalities before being 19 year-old, since january 1996 to december 2003. The statistical analysis was made with the statistical software SAS; in order to calculate the survival curve, the method employed was Kaplan-Meier and the standardized height and weight z-scores were calculated. RESULTS: In this report, there is data related to 710 patients with chronic renal failure, under conservative treatment 34.2%, dialysis 57.6% and transplant 29.5%. The end-stage renal disease incidence was of 6.5/million inhabitants. The main etiologies were obstructive uropathy 18.3%, reflux nephropathy 15.1%, hemolytic uremic syndrome 14.4%, aplasia/dysplasia/hypoplasia 13.8%, and focal segmental glomerulosclerosis 8.9%. From the patients on dialysis treatment, 62.3% were under hemodialysis, and only 37.7% on peritoneal dialysis. Live-donor sources accounted for 46.2 % of the transplants, with a 1-year patient's survival of 98.7% and a 1-year graft survival of 96.4 %, similar with both donors. CONCLUSION: The results obtained, even though they do not correspond to the total population affected and the monitoring is still insufficient, allowed us to have a profile of the chronic renal failure in our country.
Subject(s)
Kidney Failure, Chronic/therapy , Kidney Transplantation , Renal Dialysis , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Kidney Transplantation/statistics & numerical data , Male , Renal Dialysis/statistics & numerical dataABSTRACT
Hemolytic Uremic Syndrome (HUS) is the main cause of acute renal failure in children. The high percentage of patients who develop long-term sequelae constitutes an important medical concern. The identification of parameters that correlate with the degree of renal failure may be useful to plan the best treatment soon after hospitalization. Here, we investigated the functional state of neutrophils (PMN) from HUS patients on admission, before dialysis and/or transfusion, in relation to the severity of renal impairment reached during the acute period (AP). We found that all PMN activation parameters measured in severe cases of HUS (HUS AP3) were statistically lower comparing to children with mild cases of HUS (HUS AP1). As HUS PMN phenotype and dysfunction is compatible with that of cells undergoing cell death, we also studied spontaneous apoptosis. Not only were HUS PMN not apoptotic, but HUS AP3 PMN showed an increased survival. Almost all phenotypic and functional parameters measured on PMN correlated with severity. Our results revealed a marked deactivation of PMN in severe cases of HUS, and suggest that studying the functional state of PMN could be of prognostic value.
Subject(s)
Hemolytic-Uremic Syndrome/diagnosis , Hemolytic-Uremic Syndrome/physiopathology , Neutrophils/physiology , Child, Preschool , Female , Humans , Infant , Male , PrognosisABSTRACT
Thrombotic microangiopathy and acute renal failure are cardinal features of postdiarrheal hemolytic uremic syndrome (HUS). These conditions are related to endothelial and epithelial cell damage induced by Shiga toxin (Stx) through the interaction with its globotriaosyl ceramide receptor. However, inflammatory processes contribute to the pathogenesis of HUS by sensitizing cells to Stx fractalkine (FKN), a CX(3)C transmembrane chemokine expressed on epithelial and endothelial cells upon activation, is involved in the selective migration and adhesion of specific leukocyte subsets to tissues. Here, we demonstrated a selective depletion of circulating mononuclear leukocytes expressing the receptor for FKN (CX(3)CR1) in patients with HUS. We found a unique phenotype in children with HUS distinct from that seen in healthy, uremic, or infected controls, in which monocytes lost CX(3)CR1, down-modulated CD62L, and increased CD16. In addition, the CD56(dim) natural killer (NK) subpopulation was decreased, leading to an altered peripheral CD56(dim)/CD56(bright) ratio from 10.0 to 4.5. It is noteworthy that a negative correlation existed between the percentage of circulating CX(3)CR1(+) leukocytes and the severity of renal failure. Finally, CX(3)CR1(+) leukocytes were observed in renal biopsies from patients with HUS. We suggest that the interaction of CX(3)CR1(+) cells with FKN present on activated endothelial cells may contribute to renal injury in HUS.
Subject(s)
Chemokines, CX3C/metabolism , Hemolytic-Uremic Syndrome/etiology , Hemolytic-Uremic Syndrome/metabolism , Membrane Proteins/metabolism , Signal Transduction , Biopsy , CX3C Chemokine Receptor 1 , Chemokine CX3CL1 , Child, Preschool , Female , Hemolytic-Uremic Syndrome/pathology , Hemolytic-Uremic Syndrome/surgery , Humans , Immunohistochemistry , Killer Cells, Natural/cytology , Killer Cells, Natural/metabolism , L-Selectin/metabolism , Leukocyte Count , Male , Monocytes/metabolism , Receptors, Chemokine/metabolismABSTRACT
Renal disease concurrent with a Mycoplasma pneumoniae infection is uncommon. In this report we describe the clinical outcome of a 6-year-old patient who presented with a rapidly progressive glomerulonephritis that required dialysis. A kidney biopsy was performed, and the results revealed membranoprolipherative glomerulonephritis. The IgM serology was positive, and M. pneumoniae DNA was detected in a renal biopsy sample using a nested-PCR assay. The outcome was good.
Subject(s)
DNA, Bacterial/metabolism , Glomerulonephritis/microbiology , Kidney/metabolism , Mycoplasma pneumoniae/genetics , Pneumonia, Mycoplasma/diagnosis , Acute Disease , Biopsy , Child , DNA, Bacterial/genetics , Disease Progression , Glomerulonephritis/pathology , Humans , Immunoglobulin M/metabolism , Kidney/pathology , Male , Pneumonia, Mycoplasma/genetics , Pneumonia, Mycoplasma/pathology , Polymerase Chain ReactionABSTRACT
Monocytes (Mo) mediate central functions in inflammation and immunity. Different subpopulations of Mo with distinct phenotype and functional properties have been described. Here, we investigate the phenotype and function of peripheral Mo from children with hemolytic uremic syndrome (HUS). For this purpose, blood samples from patients in the acute period of HUS (HUS AP) were obtained on admission before dialysis and/or transfusion. The Mo phenotypic characterization was performed on whole blood by flow cytometry, and markers associated to biological functions were selected: CD14 accounting for lipopolysaccharide (LPS) responsiveness, CD11b for adhesion, Fc receptor for immunoglobulin G type I (FcgammaRI)/CD64 for phagocytosis and cytotoxicity, and human leukocyte antigen (HLA)-DR for antigen presentation. Some of these functions were also determined. Moreover, the percentage of CD14+ CD16+ Mo was evaluated. We found that the entire HUS AP Mo population exhibited reduced CD14, CD64, and CD11b expression and decreased LPS-induced tumor necrosis factor production and Fcgamma-dependent cytotoxicity. HUS AP showed an increased percentage of CD14+ CD16+ Mo with higher CD16 and lower CD14 levels compared with the same subset from healthy children. Moreover, the CD14++ CD16- Mo subpopulation of HUS AP had a decreased HLA-DR expression, which correlated with severity. In conclusion, the Mo population from HUS AP patients presents phenotypic and functional alterations. The contribution to the pathogenesis and the possible scenarios that led to these changes are discussed.
Subject(s)
Antigens, Differentiation/immunology , Fetal Blood/immunology , Hemolytic-Uremic Syndrome/immunology , Hemolytic-Uremic Syndrome/physiopathology , Monocytes/immunology , Cell Count , Child, Preschool , Cytotoxicity, Immunologic , Flow Cytometry , Hemolytic-Uremic Syndrome/diagnosis , Humans , Immunoglobulin Fc Fragments/immunology , Infant , Lipopolysaccharides/pharmacology , Phenotype , Tumor Necrosis Factors/immunologyABSTRACT
Experimental and clinical evidence suggest that activated neutrophils (PMN) could contribute to endothelial damage in Hemolytic Uremic Syndrome (D+HUS). Additionally, while PMN-activating cytokines and PMN-derived products have been found in D+HUS sera, we have demonstrated phenotypic alterations in D+HUS PMN compatible with a deactivation state. Here, we investigated whether D+HUS PMN were actually hyporesponsive, and explored some of the mechanisms probably involved in their derangement. Twenty-two D+HUS children were bled in the acute period, and blood samples from healthy, acute uremic and neutrophilic children were obtained as controls. We evaluated degranulation markers in response to cytokines, intracellular granule content, and reactive oxygen species (ROS) generation in circulating D+HUS and control PMN. The influence of D+HUS-derived plasma and the direct effects of Stx in vitro were evaluated on healthy donors' PMN. We found that D+HUS PMN presented reduced degranulatory capacity in response to cytokines and intracellular granule content, and decreased ROS generation. D+HUS plasma or Stx did not affect the phenotype and function of healthy donors' PMN. These results suggest that upon hospitalization D+HUS PMN are functionally impaired and show features of previous degranulation, indicating a preceding process of activation with release of ROS and proteases involved in endothelial damage.
Subject(s)
Endothelium, Vascular/immunology , Hemolytic-Uremic Syndrome/immunology , Neutrophils/immunology , Cell Degranulation/immunology , Child, Preschool , Endothelium, Vascular/physiopathology , Female , Hemolytic-Uremic Syndrome/physiopathology , Humans , Infant , Male , Neutrophil Activation/immunology , Peptide Hydrolases/analysis , Reactive Oxygen Species/analysisABSTRACT
Realizamos dosaje de eritropoyetina (EPO) sérica en niños con Síndrome Urémico-Hemolítico (SUH) para evaluar si sus niveles son adecuados. Se incluyeron diez pacientes que no había sido aún transferidos, realizando al ingreso y a los 7, 14, 21, 28 y 60 días de evolución, los siguientes controles: hemogramas, reticulocitos, plaquetas, dosaje de EPO sérica, ferritina, ferremia, capacidad total y porcentaje de saturación de transferrina, ionograma, estado ácido base, urea y creatinina. El análisis de los valores fue determinado, para cada paciente, en las muestras de sangre correspondientes a tres etapas diferenciadas. A) Previo a la primera transfusión; B) Luego de la misma, y mientras persistiera el fallo renal (creatinina > 0,7 mg/dl); C) Fase de recuperación. Presentaron oligoanuria ocho pacientes, y seis necesitaron diálisis. Todos requirieron transfusiones: siete al ingreso, y los restantes a las 24 hs, 6 y 10 días de internación, respectivamente; seis niños necesitaron transfusiones adicionales posteriormente; el promedio total fue de 1,8 +- 0,8 (1-3) por niño. El valor del cociente O/P (logaritmo de EPO observada/logaritmo de EPO previsto) al ingreso fue bajo (0,70 +- 0,08), disminuyó aún más en la etapa B (0,57 +- 0,03) y se elevó posteriormente, pero sin alcanzar valores normales (0,78 +-0,07); los valores del índice de Producción Reticulocitaria (recuento reticulocitario corregido/tiempo de maduración)siguieron un curso paralelo (0,74 +- 0,14, 0,54 +- 0,11 y 0,60 +- 0,10 respectivamente). La correlación entre valores absolutos de EPO y hematocrito mostró un comportamiento opuesto al normal, mostrando valores positivos en las tres etapas (r: 0,53, 0,36 y 0,12, respectivamente). Al comparar los resultados observados con los esperados de EPO (en términos de LogEpo), 9 de las 11 (81,8 porciento) muestras pretransfusionales presentaron valores inferiores a los esperados; en la segunda etapa todas las muestras estuvieron por debajo de los normal; en fase de recuperación, la mayoría (77,8 porciento) siguió mostrando valores bajos. En conclusión, hemos demostrado una síntesis inadecuada de EPO en niños con SUH, no comunicada previamente, que podría jugar un papel fisiopatogénico de importancia al agravar la severidad de la anemia hemolítica existente; esta síntesis inadecuada se intensifica al sumarse el efecto inhibitorio secundario a las repetidas transfusiones recibidas. La potencial utilización terapéutica de EPO recombinante en estos niños ... (AU)
Subject(s)
Hemolytic-Uremic Syndrome , Erythropoietin , Acute Kidney InjuryABSTRACT
Realizamos dosaje de eritropoyetina (EPO) sérica en niños con Síndrome Urémico-Hemolítico (SUH) para evaluar si sus niveles son adecuados. Se incluyeron diez pacientes que no había sido aún transferidos, realizando al ingreso y a los 7, 14, 21, 28 y 60 días de evolución, los siguientes controles: hemogramas, reticulocitos, plaquetas, dosaje de EPO sérica, ferritina, ferremia, capacidad total y porcentaje de saturación de transferrina, ionograma, estado ácido base, urea y creatinina. El análisis de los valores fue determinado, para cada paciente, en las muestras de sangre correspondientes a tres etapas diferenciadas. A) Previo a la primera transfusión; B) Luego de la misma, y mientras persistiera el fallo renal (creatinina > 0,7 mg/dl); C) Fase de recuperación. Presentaron oligoanuria ocho pacientes, y seis necesitaron diálisis. Todos requirieron transfusiones: siete al ingreso, y los restantes a las 24 hs, 6 y 10 días de internación, respectivamente; seis niños necesitaron transfusiones adicionales posteriormente; el promedio total fue de 1,8 +- 0,8 (1-3) por niño. El valor del cociente O/P (logaritmo de EPO observada/logaritmo de EPO previsto) al ingreso fue bajo (0,70 +- 0,08), disminuyó aún más en la etapa B (0,57 +- 0,03) y se elevó posteriormente, pero sin alcanzar valores normales (0,78 +-0,07); los valores del índice de Producción Reticulocitaria (recuento reticulocitario corregido/tiempo de maduración)siguieron un curso paralelo (0,74 +- 0,14, 0,54 +- 0,11 y 0,60 +- 0,10 respectivamente). La correlación entre valores absolutos de EPO y hematocrito mostró un comportamiento opuesto al normal, mostrando valores positivos en las tres etapas (r: 0,53, 0,36 y 0,12, respectivamente). Al comparar los resultados observados con los esperados de EPO (en términos de LogEpo), 9 de las 11 (81,8 porciento) muestras pretransfusionales presentaron valores inferiores a los esperados; en la segunda etapa todas las muestras estuvieron por debajo de los normal; en fase de recuperación, la mayoría (77,8 porciento) siguió mostrando valores bajos. En conclusión, hemos demostrado una síntesis inadecuada de EPO en niños con SUH, no comunicada previamente, que podría jugar un papel fisiopatogénico de importancia al agravar la severidad de la anemia hemolítica existente; esta síntesis inadecuada se intensifica al sumarse el efecto inhibitorio secundario a las repetidas transfusiones recibidas. La potencial utilización terapéutica de EPO recombinante en estos niños ...
Subject(s)
Hemolytic-Uremic Syndrome , Acute Kidney Injury , ErythropoietinABSTRACT
Se presenta una paciente de 8 años de edad, de sexo femenino, con hipertensión arterial severa secundaria a estenosis de la arteria renal izquierda. Los estudios complementarios revelaron buena funcionalidad del riñón afectado y por la ubicación de la estenosis se realizó cirugía de autotransplante con muy buena evolución posterior (AU)
Subject(s)
Humans , Female , Kidney Transplantation/methods , Transplantation, Autologous/methods , Hypertension, Renovascular/surgery , Hypertension, Renovascular/drug therapy , Hypertension, Renovascular/therapy , Hypertension/complications , Renin/diagnosis , Iliac Vein/surgery , Renal Veins/surgery , High Pressure Neurological Syndrome/etiologyABSTRACT
Se presenta una paciente de 8 años de edad, de sexo femenino, con hipertensión arterial severa secundaria a estenosis de la arteria renal izquierda. Los estudios complementarios revelaron buena funcionalidad del riñón afectado y por la ubicación de la estenosis se realizó cirugía de autotransplante con muy buena evolución posterior
Subject(s)
Humans , Female , Hypertension, Renovascular/surgery , Kidney Transplantation , Transplantation, Autologous , High Pressure Neurological Syndrome/etiology , Hypertension, Renovascular/drug therapy , Hypertension, Renovascular/therapy , Hypertension/complications , Renal Veins/surgery , Renin , Iliac Vein/surgeryABSTRACT
Introducción.La elevada incidencia de infección urinaria(I.U)en pediatría,junto al aumento de la resistencia de las cepas de Escherichia coli en nuestro medio,determina la necesidad de buscar nuevas opciones terapeúticas.Para ello se comparado la efectividad y tolerancia de ceflacor(CCL)vs cefradroxilo(CDX)para el tratamiento de la I.U en pacientes pediátricos.Material y Métodos.Se trataron 60 pacientes de ambos sexos,con edades comprendidas entre 7 y 156 meses portadores de I.U.Se realizó un estudio multicéntrico comparativo,al azar,en el que se utilizó CDX a 30 mg/kg/día,ambos cada 12 horas por vía oral.La duración del tratamiento fue de 3 y 10 días para infección urinaria baja(I.U.B) e infección urinaria alta,respectivamente,de acuerdo a los criterios de localización utilizados.Conclusiones.Ambos antimicrobianos demostraron ser efectivos para el tratamiento de la I.U presentando los dos muy buena tolerancia oral.CCL presentó mejor actividad frente a las cepas de E.coli aisladas,por lo que consideramos que es una alternativa efectiva para el tratamiento de la IU en pediatría
Subject(s)
Infant , Child, Preschool , Urinary Tract Infections/therapy , Cefaclor/administration & dosage , Cefaclor/therapeutic use , Escherichia coli/drug effects , Escherichia coli/immunology , PediatricsABSTRACT
Introducción.La elevada incidencia de infección urinaria(I.U)en pediatría,junto al aumento de la resistencia de las cepas de Escherichia coli en nuestro medio,determina la necesidad de buscar nuevas opciones terapeúticas.Para ello se comparado la efectividad y tolerancia de ceflacor(CCL)vs cefradroxilo(CDX)para el tratamiento de la I.U en pacientes pediátricos.Material y Métodos.Se trataron 60 pacientes de ambos sexos,con edades comprendidas entre 7 y 156 meses portadores de I.U.Se realizó un estudio multicéntrico comparativo,al azar,en el que se utilizó CDX a 30 mg/kg/día,ambos cada 12 horas por vía oral.La duración del tratamiento fue de 3 y 10 días para infección urinaria baja(I.U.B) e infección urinaria alta,respectivamente,de acuerdo a los criterios de localización utilizados.Conclusiones.Ambos antimicrobianos demostraron ser efectivos para el tratamiento de la I.U presentando los dos muy buena tolerancia oral.CCL presentó mejor actividad frente a las cepas de E.coli aisladas,por lo que consideramos que es una alternativa efectiva para el tratamiento de la IU en pediatría
