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BACKGROUND: Early fluid management in patients with advanced chronic kidney disease (CKD) and sepsis-induced hypotension is challenging with limited evidence to support treatment recommendations. We aimed to compare an early restrictive versus liberal fluid management for sepsis-induced hypotension in patients with advanced CKD. METHODS: This post-hoc analysis included patients with advanced CKD (eGFR of less than 30 mL/min/1.73 m2 or history of end-stage renal disease on chronic dialysis) from the crystalloid liberal or vasopressor early resuscitation in sepsis (CLOVERS) trial. The primary endpoint was death from any cause before discharge home by day 90. RESULTS: Of 1563 participants enrolled in the CLOVERS trial, 196 participants had advanced CKD (45% on chronic dialysis), with 92 participants randomly assigned to the restrictive treatment group and 104 assigned to the liberal fluid group. Death from any cause before discharge home by day 90 occurred significantly less often in the restrictive fluid group compared with the liberal fluid group (20 [21.7%] vs. 41 [39.4%], HR 0.5, 95% CI 0.29-0.85). Participants in the restrictive fluid group had more vasopressor-free days (19.7 ± 10.4 days vs. 15.4 ± 12.6 days; mean difference 4.3 days, 95% CI, 1.0-7.5) and ventilator-free days by day 28 (21.0 ± 11.8 vs. 16.5 ± 13.6 days; mean difference 4.5 days, 95% CI, 0.9-8.1). CONCLUSIONS: In patients with advanced CKD and sepsis-induced hypotension, an early restrictive fluid strategy, prioritizing vasopressor use, was associated with a lower risk of death from any cause before discharge home by day 90 as compared with an early liberal fluid strategy. TRIAL REGISTRATION: NCT03434028 (2018-02-09), BioLINCC 14149.
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Fluidoterapia , Hipotensión , Insuficiencia Renal Crónica , Sepsis , Humanos , Sepsis/complicaciones , Sepsis/terapia , Masculino , Femenino , Persona de Mediana Edad , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/complicaciones , Anciano , Fluidoterapia/métodos , Hipotensión/etiología , Hipotensión/terapiaRESUMEN
OBJECTIVES: Patients with systemic rheumatic diseases (SRDs) are at risk of admission to the intensive care unit (ICU). Data concerning these critically ill patients are limited to few retrospective studies. METHODS: This is a single-centre retrospective study of patients with SRDs admitted to an ICU at the Vienna General Hospital between 2012 and 2020. Single-predictor and multiple logistic regression analysis was performed to identify potential outcome determinants. RESULTS: A total of 144 patients accounting for 192 ICU admissions were included. Connective tissue diseases (CTDs), vasculitides and rheumatoid arthritis were the most common SRDs requiring ICU admission. Leading causes for ICU admission were respiratory failure and shock, as reflected by a high number of patients requiring mechanical ventilation (60.4%) and vasopressor therapy (72.9%). Overall, 29.2% of admissions were due to SRD-related critical illness. In 70.8% patients, co-existent SRD not responsible for the acute critical illness was documented. When comparing these subgroups, CTDs and vasculitides had a higher frequency in the patients with SRD-related critical illness. In a significantly higher proportion of patients in the SRD-related subgroup, diagnosis of SRD was made at the ICU. ICU and 6-month mortality in the overall population was 20.3% and 38.5%, respectively. Age, glucocorticoid therapy prior to hospital admission and disease severity were associated with poor outcome. CONCLUSIONS: In this study, respiratory failure was the leading cause of ICU admission as reflected by high rates of required mechanical ventilation. Despite considerable severity of critical illness, survival rates were comparable to a general ICU population.
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Insuficiencia Respiratoria , Enfermedades Reumáticas , Vasculitis , Humanos , Enfermedad Crítica/terapia , Estudios Retrospectivos , Unidades de Cuidados Intensivos , Enfermedades Reumáticas/epidemiología , Enfermedades Reumáticas/terapia , Enfermedades Reumáticas/complicaciones , Insuficiencia Respiratoria/epidemiología , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Vasculitis/complicacionesRESUMEN
Chronic thoracic venous occlusion (CTVO) as a result of repeated or prolonged central venous catheter insertion represents a significant problem in catheter-dependent patients. Different endovascular techniques techniques have been utilised for CTVO recanalization. The Surfacer® Inside-out® system represents a new approach to restore right-sided central venous access in CTVO by the inside-out recanalization technique. Standard approach for device implantation is through right femoral vein. In this case report, we report the first case to our knowledge of dialysis access restoration with Surfacer® system implantation via an unconventional and non-standard route by a transcollateral approach in a patient with exhausted vascular access options.
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Cateterismo Venoso Central , Catéteres Venosos Centrales , Humanos , Diálisis Renal , Catéteres de Permanencia , Resultado del Tratamiento , Vena Femoral/diagnóstico por imagenRESUMEN
OBJECTIVES: In critically ill patients requiring mechanical ventilation for at least 21 days, 1-year mortality can be estimated using the ProVent score, calculated from four variables (age, platelet count, vasopressor use and renal replacement therapy). We aimed to externally validate discrimination and calibration of the ProVent score and, if necessary, to update its underlying regression model. DESIGN: Retrospective, observational, single-centre study. SETTING: 11 intensive care units at one tertiary academic hospital. PATIENTS: 780 critically ill adult patients receiving invasive mechanical ventilation for at least 21 days. PRIMARY OUTCOME MEASURE: 1-year mortality after intensive care unit discharge. RESULTS: 380 patients (49%) had died after 1 year. One-year mortality for ProVent scores from 0 to 5 were: 15%, 27%, 57%, 66%, 72% and 76%. Area under the receiver operating characteristic curve of the ProVent probability model was 0.76 (95% CI 0.72 to 0.79), calibration intercept was -0.43 (95% CI -0.59 to -0.27) and calibration slope was 0.76 (95% CI 0.62 to 0.89). Model recalibration and extension by inclusion of three additional predictors (total bilirubin concentration, enteral nutrition and surgical status) improved model discrimination and calibration. Decision curve analysis demonstrated that the original ProVent model had negative net benefit, which was avoided with the extended ProVent model. CONCLUSIONS: The ProVent probability model had adequate discrimination but was miscalibrated in our patient cohort and, as such, could potentially be harmful. Use of the extended ProVent score developed by us could possibly alleviate this concern.
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Enfermedad Crítica , Respiración Artificial , Adulto , Austria/epidemiología , Bilirrubina , Enfermedad Crítica/terapia , Humanos , Unidades de Cuidados Intensivos , Estudios RetrospectivosRESUMEN
Vitamin D deficiency is frequent in cancer patients and a risk factor for morbidity and mortality during critical illness. This single-center retrospective study analyzed 25-hydroxyvitamin D levels in critically ill cancer patients (n = 178; hematologic, n = 108; solid, n = 70) enrolled in a prospective ICU registry. The primary analysis was the prevalence of vitamin D deficiency (<20 ng/mL) and the severe deficiency (≤12 ng/mL). Secondary analyses included risk factors for vitamin D deficiency and its impact on ICU, hospital, and 1-year mortality. The prevalence of vitamin D deficiency and severe deficiency was 74% (95% CI: 67-80%) and 54% (95% CI: 47-61%). Younger age, relapsed/refractory disease, and a higher sepsis-related organ failure assessment (SOFA) score were independent risk factors for vitamin D deficiency (p < 0.05). After adjusting for relapsed/refractory disease, infection, the SOFA score, and the early need for life-supporting interventions, severe vitamin D deficiency was an independent predictor of hospital mortality (OR: 2.21, 95% CI: 1.03-4.72, p = 0.04) and 1-year mortality (OR: 3.40, 95% CI: 1.50-7.71, p < 0.01), but not of ICU mortality. Conclusion: Vitamin D deficiency is common in critically ill cancer patients requiring ICU admission, but its impact on short-term mortality in this group is uncertain. The observed association of severe vitamin D deficiency with the post-ICU outcome warrants clinical consideration and further study.
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Enfermedad Crítica/epidemiología , Unidades de Cuidados Intensivos/estadística & datos numéricos , Deficiencia de Vitamina D/epidemiología , Adulto , Anciano , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/mortalidad , Prevalencia , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/mortalidadRESUMEN
PURPOSE: To report the device performance and safety for the Surfacer Inside-Out access catheter system in patients with thoracic central venous obstruction (TCVO) requiring central venous access (CVA). MATERIALS AND METHODS: Five sites prospectively enrolled 30 patients requiring a tunneled dialysis catheter between February 2017 and September 2018 in the SAVE (Surfacer System to Facilitate Access in Venous Obstructions) registry. Patient demographics, medical history, and type of TCVO were documented at enrollment. Device performance and adverse events were collected during the procedure and upon hospital discharge. Twenty-nine of the 30 patients enrolled required CVA for hemodialysis. Retrospective classification of TCVOs according to SIR reporting standards showed 9 patients (30%) had Type 4 obstructions, 8 (26.7%) had Type 3, 5 (16.7%) had Type 2, and 8 (26.7%) had Type 1 obstruction. RESULTS: Central venous catheters (CVCs) were successfully placed in 29 of 30 patients (96.7%). The procedure was discontinued in 1 patient due to vascular anatomical tortuosity. All 29 patients with successful CVC placement achieved adequate catheter patency and tip positioning. There were no device-related adverse events, catheter malposition, or intra- or postprocedural complications. Mean time from device insertion to removal for the 29 patients who successfully completed the procedure was 24 ± 14.9 (range, 6-70) minutes. Mean fluoroscopy time was 6.8 ± 4.5 (range, 2.2-25.5) minutes. CONCLUSIONS: The Surfacer Inside-Out procedure provided an alternative option to restore right-sided CVA in patients with TCVO.
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Venas Braquiocefálicas , Cateterismo Venoso Central/instrumentación , Catéteres de Permanencia , Catéteres Venosos Centrales , Venas Yugulares , Diálisis Renal , Vena Subclavia , Enfermedades Vasculares , Vena Cava Superior , Adulto , Anciano , Anciano de 80 o más Años , Venas Braquiocefálicas/diagnóstico por imagen , Cateterismo Venoso Central/efectos adversos , Constricción Patológica , Diseño de Equipo , Europa (Continente) , Femenino , Humanos , Venas Yugulares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros , América del Sur , Vena Subclavia/diagnóstico por imagen , Enfermedades Vasculares/diagnóstico por imagen , Enfermedades Vasculares/etiología , Vena Cava Superior/diagnóstico por imagenRESUMEN
Elevated levels of thyroid-stimulating-hormone (TSH) are associated with reduced glomerular filtration rate (GFR) and increased risk of developing chronic kidney disease even in euthyroid patients. Thyroid hormone replacement therapy has been shown to delay progression to end-stage renal disease in sub-clinically hypothyroid patients with renal insufficiency. However, such associations after kidney transplantation were never investigated. In this study the association of thyroid hormones and estimated GFR (eGFR) in euthyroid patients after kidney transplantation was analyzed. In total 398 kidney transplant recipients were assessed retrospectively and association between thyroid and kidney function parameters at and between defined time points, 12 and 24 months after transplantation, was studied. A significant inverse association was shown for TSH changes and eGFR over time between months 12 and 24 post transplantation. For each increase of TSH by 1 µIU/mL, eGFR decreased by 1.34 mL/min [95% CI, -2.51 to -0.16; p = 0.03], corresponding to 2.2% eGFR decline, within 12 months. At selected time points 12 and 24 months post transplantation, however, TSH was not associated with eGFR. In conclusion, an increase in TSH between 12 and 24 months after kidney transplantation leads to a significant decrease in eGFR, which strengthens the concept of a kidney-thyroid-axis.
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Tasa de Filtración Glomerular , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/sangre , Insuficiencia Renal/sangre , Tirotropina/sangre , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/fisiopatología , Insuficiencia Renal/fisiopatología , Receptores de TrasplantesRESUMEN
RATIONALE & OBJECTIVE: Left-sided internal jugular and all subclavian central venous catheters (CVCs) cause thoracic central vein occlusions (TCVOs) more often than right-sided internal jugular catheters. To enable right-sided CVC placement in patients with TCVO, an inside-out access (IOA) approach was established at 3 vascular access centers in Europe involving use of a novel IOA device advanced from the right femoral vein. In the current analysis, we assessed the eligibility and success rate of this IOA approach in a cohort of patients with TCVO requiring a tunneled dialysis catheter. STUDY DESIGN: Retrospective multicenter observational study. SETTING & PARTICIPANTS: 36 patients with TCVO treated in Vienna, Austria; Oxford, England; or Cologne, Germany, who required hemodialysis access between July 2016 and June 2018. EXPOSURE: Application of the IOA approach to gain vascular access. OUTCOME: The primary end point was the success rate of passing the TCVO to gain dialysis access using the IOA approach. Secondary end points were catheter patency at 3 months and procedure-related complications (early infections, bleeding, hematoma, and pericardial effusions). ANALYTICAL APPROACH: Descriptive statistics to characterize eligibility, success rate, and complications of the IOA approach. RESULTS: 36 patients with TCVO and history of multiple CVCs and arteriovenous fistulas were referred to the participating centers for vascular access. 32 (89%) patients were eligible for the IOA approach. 39 treatments were performed, with 7 patients undergoing the IOA procedure a second time more than 3 months after initial CVC placement. Dialysis access was established successfully in 38 of 39 (97%) implementations of the IOA procedure. Median intervention time was 43 minutes. No complications occurred. LIMITATIONS: No comparison to other methods to place CVCs and the observational study design. CONCLUSIONS: The IOA approach is a promising method to enable rapid access to the right jugular vein in the setting of pre-existing TCVO. Additional experience is needed to understand the generalizability of these observations.
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Cateterismo Venoso Central/efectos adversos , Catéteres de Permanencia/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Venas Yugulares/diagnóstico por imagen , Diálisis Renal/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Cateterismo Venoso Central/tendencias , Catéteres de Permanencia/tendencias , Catéteres Venosos Centrales/tendencias , Femenino , Humanos , Venas Yugulares/cirugía , Masculino , Persona de Mediana Edad , Diálisis Renal/tendencias , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Complement factor C3 represents the central component of the complement cascade and its activation split product C3a plays an important role in inflammation and disease. Many human disorders are linked to dysregulation of the complement system and alteration in interaction molecules. Therefore, various therapeutic approaches to act on the complement system have been initiated. METHODS AND RESULTS: Aiming to develop a tool to eliminate C3a/C3 from the circulation, in a first step a high affine murine monoclonal antibody (mAb) (3F7E2-mAb) was generated against complement factor C3 and selected for binding to the C3a region to serve as immunoaffinity reagent. Functional testing of the 3F7E2-mAb revealed an inhibition of Zymosan-induced cleavage of C3a from C3. Subsequently, a C3a/C3 specific 3F7E2-immunoaffinity column was developed and apheresis of C3a/C3 and associates was performed. Finally, a proteomic analysis was carried out for identification of apheresis products. C3a/C3 was liberated from the 3F7E2-column together with 278 proteins. C3a/C3 interaction specificity was validated by using a haptoglobin immunoaffinity column as control and biostatistic analysis revealed 39 true C3a/C3 interactants. CONCLUSION: A novel and functionally active mAb was developed against complement factor C3a/C3 and used in a specific immunoaffinity column that allows apheresis of C3a/C3 and associates and their identification by proteomic analysis. This methodological approach of developing specific antibodies that can be used as immunoaffinity reagents to design immunoaffinity columns for elimination and further identification of associated proteins could open new avenues for the development of tailored immunotherapy in various complement-mediated or autoimmune diseases.
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The plasma soluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker for focal segmental glomerulosclerosis (FSGS), but its value is under discussion because of ambiguous results arising from different ELISA methods in previous studies. The aim of this study was to compare diagnostic performance of two leading suPAR ELISA kits and examine four objectives in 146 subjects: (1) plasma suPAR levels according to glomerular disease (primary, secondary and recurrent FSGS after kidney transplantation, other glomerulonephritis) and in healthy controls; (2) suPAR levels based on glomerular filtration rate; (3) sensitivity and specificity of suPAR for FSGS diagnosis and determination of optimal cut-offs; (4) suPAR as prognostic tool. Patients with FSGS showed significant higher suPAR values than patients with other glomerulonephritis and healthy individuals. This applied to subjects with and without chronic kidney disease. Although both suPARnostic™ assay and Quantikine Human uPAR ELISA Kit exerted high sensitivity and specificity for FSGS diagnosis, their cut-off values of 4.644 ng/mL and 2.789 ng/mL were significantly different. Higher suPAR was furthermore predictive for progression to end-stage renal disease. In summary, suPAR values must be interpreted in the context of population and test methods used. Knowing test specific cut-offs makes suPAR a valuable biomarker for FSGS.
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Glomeruloesclerosis Focal y Segmentaria/sangre , Receptores del Activador de Plasminógeno Tipo Uroquinasa/sangre , Adulto , Biomarcadores/sangre , Estudios Transversales , Femenino , Tasa de Filtración Glomerular/fisiología , Glomerulonefritis/sangre , Glomeruloesclerosis Focal y Segmentaria/diagnóstico , Glomeruloesclerosis Focal y Segmentaria/patología , Humanos , Fallo Renal Crónico/sangre , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Estudios RetrospectivosRESUMEN
Correction to: Wien Klin Wochenschr 2018 https://doi.org/10.1007/s00508-018-1381-5 Unfortunately, the original version of this article contained two mistakes.The text passage "It should be mentioned here that in the case of apixaban, dose adjustment is not based on GFR. A lower dosage of apixaban .
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Strongyloides stercoralis is not hyperendemic in European countries but has been increasing in prevalence due to migration and travel. The infection is characterized by a mostly asymptomatic course or nonspecific symptoms in healthy subjects. However, immunosuppression or chemotherapy have been described as leading triggers for Strongyloides stercoralis hyperinfection syndrome and may have a fatal course. A post hoc analysis was performed among renal transplant patients during a 5-year period. Plasma samples of two hundred kidney allograft recipients were retrospectively analyzed for Strongyloides stercoralis seropositivity by established ELISA testing. Positive Strongyloides stercoralis serology was found in 3% of allograft recipients. One patient developed a life-threatening hyperinfection syndrome. His Strongyloides IgG signal had been elevated for years before the outbreak of the disease. Stronglyoides infections in transplant recipients are an important issue that physicians also in Central Europe should be aware of, given the risk of hyperinfection syndrome and the challenges in clinical diagnosis. Our study suggests that recipient and donor screening should be recommended in kidney transplantation programs in Central Europe as Strongyloides infection rates increase and its prevalence may be underestimated. Further research is needed to understand why some Strongyloides stercoralis seropositive individuals develop hyperinfection syndrome and others do not.
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Trasplante de Riñón/estadística & datos numéricos , Strongyloides stercoralis , Estrongiloidiasis/epidemiología , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Receptores de Trasplantes/estadística & datos numéricos , Adulto , Anciano , Animales , Estudios de Casos y Controles , Europa (Continente)/epidemiología , Humanos , Terapia de Inmunosupresión/efectos adversos , Terapia de Inmunosupresión/estadística & datos numéricos , Trasplante de Riñón/efectos adversos , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Estudios Seroepidemiológicos , Strongyloides stercoralis/inmunología , Strongyloides stercoralis/aislamiento & purificación , Estrongiloidiasis/sangre , Trasplante HomólogoRESUMEN
The non-vitamin K antagonist oral anticoagulants (NOACs) have considerably changed clinical practice and are increasingly being used as an alternative to vitamin K antagonists (VKAs) for 3 main reasons: 1) an improved benefit-risk ratio (in particular lower rates of intracranial bleeding), 2) a more predictable effect without the need for routine monitoring, and 3) fewer food and drug interactions compared with VKAs. Currently, there are four NOACs available: the factor Xa inhibitors apixaban, edoxaban, and rivaroxaban, and the thrombin inhibitor dabigatran. This consensus paper reviews the properties and usage of NOACs in a number of high-risk patient populations, such as patients with chronic kidney disease, patients ≥80 years of age and others and provides guidance for the use of NOACs in patients at risk of bleeding.
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Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Accidente Cerebrovascular , Administración Oral , Anciano de 80 o más Años , Dabigatrán , Hemorragia , Humanos , RivaroxabánAsunto(s)
Investigación Biomédica/tendencias , Factor de Impacto de la Revista , Publicaciones Periódicas como Asunto/tendencias , Ciencia/tendencias , Investigación Biomédica/estadística & datos numéricos , Publicaciones Periódicas como Asunto/estadística & datos numéricos , Ciencia/estadística & datos numéricos , TurquíaRESUMEN
BACKGROUND: Baseline comorbidities influence patient outcomes in renal transplantation. Identification of high-risk recipients for patient death and early allograft loss might lead to superior stratification. MATERIAL AND METHODS: In this retrospective study, risk stratification models were developed in a cohort of 392 kidney transplant recipients and validated in an independent cohort to predict short-term (2 year) outcomes. RESULTS: Peripheral arterial disease [OR 7·7 (95% confidence interval (CI): 2·45-24·60); P < 0·001], use of oral anticoagulation [OR 18·68 (95% CI: 3·77-92·46); P < 0·0001], smoking [OR 5·15 (95% CI: 1·67-15·84); P = 0·004], recipient age > 60 years [OR 7·28 (95% CI: 2·33-22·69; P = 0·001)], serum albumin < 40 g/L [OR 5·08 (95% CI: 1·82-14·19); P = 0·002], serum calcium ≥ 2·42 mM [OR 6·47 (95% CI: 1·37-30·58); P = 0·02] living donation [OR 2·95, (95% CI: 0·31-28·29); P = 0·34)] and previous haemodialysis [OR 3·33, (95% CI: 0·39-28·11); P = 0·27)] were included in the model. The validated model discriminated between low- (< 3 points) and high-risk recipients (> 8·5 points) with mortality rates of 0% vs. 54%. The comparison of the model with the Charlson comorbidity index (CCI) yielded significantly better receiver operating characteristic (ROC) areas (Novel Score ROC: 0·87 vs. CCI: 0·72, P = 0·0012). Early allograft loss was associated with presensitization [OR 3·02 (95% CI: 1·29-7·09); P = 0·011] and presence of hepatitis C antibodies [OR 2·42 (95% CI: 1·09-5·34); P = 0·029]. A risk model (ROC: 0·62) for allograft loss could not be developed. CONCLUSION: Risk stratification based on the novel score might identify high-risk recipients with disproportional risk of early patient death and lead to optimized strategies.
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Trasplante de Riñón/mortalidad , Adulto , Femenino , Supervivencia de Injerto/fisiología , Humanos , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios/métodos , Cuidados Preoperatorios/mortalidad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo/métodos , Análisis de Supervivencia , Trasplante Homólogo/mortalidadRESUMEN
In this study we examined whether low-density lipoprotein (LDL) receptor family members represent a link between blood flow characteristics and modified low-density lipoproteins involved in endothelial injury, a pivotal factor in atherogenesis. We demonstrated the expression of pro-atherogenic LDL receptor relative (LR11) for the first time in human coronary artery endothelial cells (HCAEC) in vitro and in vivo. Next, LR11 expression and regulation were explored in HCAEC cultured conventionally or on the inner surface of hollow fiber capillaries under exposure to shear stress for 10 days in the presence or absence of LDL. There was no LR11 expression under static conditions. When exposed to chronic low shear stress (2.5 dynes/cm²) transmembrane and soluble endothelial-LR11 were detected in high levels irrespective of the type of LDL added (carbamylated or native). In contrast, chronic high shear stress (25 dynes/cm²) inhibited the LR11-inducing effect of LDL such that transmembrane and soluble LR11 expression became non-detectable with native LDL. Carbamylated LDL significantly counteracted this atheroprotective effect of high shear stress as shown by lower, yet sustained expression of soluble and transmembrane LR11. Oxidised LDL showed similar effects compared to carbamylated LDL but caused significantly lower LR11 expression under chronic high shear stress. Medium from HCAEC under LR11-inducing conditions enhanced vascular smooth muscle cell migration, which was abrogated by the anti-LR11 antibody. Expression of LR11 depended entirely on p38MAPK phosphorylation. We conclude that coronary endothelial LR11 expression modulated by LDL and chronic shear stress contributes to atherogenesis. LR11 and p38MAPK are potential targets for prevention of atherosclerosis.
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Aterosclerosis/metabolismo , Enfermedad de la Arteria Coronaria/metabolismo , Vasos Coronarios/metabolismo , Células Endoteliales/metabolismo , Proteínas Relacionadas con Receptor de LDL/metabolismo , Lipoproteínas LDL/metabolismo , Mecanotransducción Celular , Proteínas de Transporte de Membrana/metabolismo , Aterosclerosis/genética , Aterosclerosis/patología , Movimiento Celular , Proliferación Celular , Células Cultivadas , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/patología , Vasos Coronarios/patología , Medios de Cultivo Condicionados/metabolismo , Células Endoteliales/patología , Activación Enzimática , Humanos , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Fosforilación , Estrés Mecánico , Factores de Tiempo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
The involvement of autoantibodies to human lysosome-associated membrane protein-2 (hLAMP-2) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is controversial because of the absence of confirmatory data subsequent to the initial reports of their high prevalence in this disease. We characterized three assays for anti-hLAMP-2 antibodies: ELISA and Western blotting assays using unglycosylated recombinant hLAMP-2 expressed in Escherichia coli, and an indirect immunofluorescence assay using stably transfected ldlD cells that expressed glycosylated full-length hLAMP-2 on the plasma membrane. The assays detected autoantibodies to hLAMP-2 in human sera reproducibly and with comparable sensitivity and the assays gave the same results in 80.5% of the test panel of 40 selected positive and negative sera. In untreated patients at presentation, the frequencies of autoantibodies to LAMP-2 were 89%, 91%, and 80%, respectively, among three groups of patients with ANCA-associated vasculitis from Vienna, Austria (n=19); Groningen, the Netherlands (n=50) and Cambridge, United Kingdom (n=53). Prevalence of LAMP-2 autoantibodies was similar in both those with myeloperoxidase-ANCA and proteinase 3-ANCA. Furthermore, we detected LAMP-2 autoantibodies in two ANCA-negative patients. LAMP-2 autoantibodies rapidly became undetectable after the initiation of immunosuppressive treatment and frequently became detectable again during clinical relapse. We conclude that when robust assays are used, circulating autoantibodies to hLAMP-2 can be detected in most European patients with ANCA-associated vasculitis. Large-scale prospective studies are now needed to determine whether they are pathogenic or merely an epiphenomenon.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/sangre , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Autoanticuerpos/sangre , Proteínas de Membrana de los Lisosomas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Austria , Western Blotting , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Proteína 2 de la Membrana Asociada a los Lisosomas , Persona de Mediana Edad , Mieloblastina/inmunología , Países Bajos , Peroxidasa/inmunología , Prevalencia , Sensibilidad y Especificidad , Reino UnidoRESUMEN
BACKGROUND: Renal dysfunction confers a grave prognosis for patients with congestive heart failure (CHF); even small increases in plasma creatinine are associated with excess mortality. Little, however, is known about prognostic indices and outcome in patients with CHF who (sub-)acutely progress to dialysis dependency. DESIGN AND SETTING: We evaluated prognostic indices in a retrospective cohort analysis of non-critically ill patients with CHF who (sub-)acutely progressed to dialysis-dependent renal failure. PATIENTS AND METHODS: 46 patients (95% ischemic cardiomyopathy) with CHF (NYHA III-IV) with dialysis-dependent renal failure (acute and acute-to-chronic renal failure) were analyzed. Demographic factors and patient characteristics, of cardiac function parameters and renal parameters were recorded longitudinally. MAIN RESULTS: CHF patients progressing to dialysis- dependent renal failure had a grave prognosis: median survival time was 95 days, mean survival 444 days. None of the known factors except age was associated with a worse outcome in CHF patients. LV/RV dysfunction, high plasma NT-pro-BNP, C-reactive protein, low albumin and body-mass index did not turn out to be prognostic indicators. The only factors indicating improved survival were recovery of renal function and low hemoglobin. CONCLUSION: Non-critically ill CHF patients with (sub-)acute renal dysfunction progressing to dialysis dependency have a grave prognosis. Renal failure itself had such a strong prognostic impact that conventional factors such as poor myocardial function or inflammation were concealed. Recovery of renal function and, surprisingly, anemia were beneficial factors. Alternative treatment strategies must be designed to improve the devastating prognosis for this special subset of patients with CHF.
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Lesión Renal Aguda/terapia , Insuficiencia Cardíaca/terapia , Isquemia Miocárdica/terapia , Diálisis Renal , Lesión Renal Aguda/sangre , Lesión Renal Aguda/mortalidad , Anciano , Austria , Creatinina/sangre , Progresión de la Enfermedad , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/mortalidad , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/sangre , Isquemia Miocárdica/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
AIM: Clostridium difficile infection is primarily a nosocomial infection but asymptomatic carriers of Clostridium difficile can be found in up to 5% of the general population. Ampicillin, cephalosporins and clindamycin are the antibiotics that are most frequently associated with Clostridium difficile-associated diarrhea or colitis. Little is known about acute renal failure as a consequence of Clostridium difficile-associated diarrhea. METHODS: In this case report, we describe the course of Clostridium difficile-associated diarrhea in an 82-year-old patient developing acute renal failure. Stopping the offending agent and symptomatic therapy brought a rapid improvement of diarrhea and acute renal failure, full recovery was gained 18 d after admission. In a systematic review we looked for links between the two conditions. RESULTS: The link between Clostridium difficile-associated diarrhea and acute renal failure in our patient was most likely volume depletion. However, in experimental studies a direct influence of Clostridium difficile toxins on renal duct cells could be shown. CONCLUSION: Rapid diagnosis, nonspecific supportive treatment and specific antibiotic treatment, especially in the elderly, may lower excess mortality Clostridium difficile-associated diarrhea and renal failure being possible complications.