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Many hypotheses could explain the mortality decrease observed using hemodiafiltration, such as reduction of intradialytic hypotension and more efficient toxin removal. We led a systematic analysis of representative uremic toxin removal with hemodialysis (HD), online postdilution hemodiafiltration (postHDF) and online predilution hemodiafiltration (preHDF), in a single-center crossover and prospective observational study. The primary outcome was the reduction ratio of uremic toxins of the three categories defined by the Eutox group. Twenty-six patients were treated by those three techniques of extra renal epuration. Mean Kt/Vurea was not different between the treatment methods. Mean reduction ratio of beta2microglobulin was significantly higher for both HDF treatments than for HD (p < 0.001). Myoglobin, kappa, and lambda free light chain reduction ratio was significantly different between the modes: 37.75 ± 11.95%, 45.31 ± 11% and 61.22 ± 10.56%/57.21 ± 12.5%, 63.53 ± 7.93%, and 68.40 ± 11.79%/29.12 ± 8.44%, 34.73 ± 9.01%, and 45.55 ± 12.31% HD, preHDF, and postHDF, respectively (p < 0.001). Mean protein-bound solutes reduction ratio was not different between the different treatments except for PCS with a higher reduction ratio during HDF treatments. Mean albumin loss was always less than 2 g. HDF improved removal of middle molecules but had no effect on indoles concentration without any difference between synthetic dialysis membranes.
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INTRODUCTION: There is no feasible benchmark in daily routine to estimate the hydration status of haemodialysis patients, which is essential to their management. OBJECTIVE: We performed a study in haemodialysis patients to assess the diagnostic performance of pulmonary ultrasound and clinical examination for the evaluation of fluid overload using transthoracic echocardiography as a gold standard. METHODS: Thirty-one patients receiving chronic haemodialysis patients were included. Evaluation of hydration status was assessed weekly before haemodialysis sessions using clinical and Echo Comet Score from pulmonary ultrasound and transthoracic echocardiography (reference method). RESULTS: Five patients had a transthoracic echocardiography overload. Compared with transthoracic echocardiography, the diagnostic performance of the clinical overload score has a sensitivity of 100%, a specificity of 77%, a positive predictive value of 50% and a negative predictive value of 100% with a κ of 0.79. Only orthopnoea (P=0.008), jugular turgor (P=0.005) and hepatic-jugular reflux (P=0.008) were significantly associated with transthoracic echocardiography overload diagnosis. The diagnostic performance of Echo Comet Score by pulmonary ultrasound has a sensitivity of 80%, a specificity of 58%, a positive predictive value of 26% and a negative predictive value of 94%. Ten patients (32.3%) had an increase of extravascular pulmonary water without evidence of transthoracic echocardiography or clinical overload. CONCLUSIONS: Our clinical score has a convincing diagnostic performance compared to transthoracic echocardiography and could be easily used in daily clinical routine to adjust dry weight. The evaluation of the overload using pulmonary ultrasound seems poorly correlated with the overload evaluated by transthoracic echocardiography. Extravascular pulmonary water undetected by clinical examination and transthoracic echocardiography remains a parameter that requires further investigation.
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Diálisis Renal , Desequilibrio Hidroelectrolítico , Ecocardiografía , Humanos , Pulmón/diagnóstico por imagen , Diálisis Renal/efectos adversos , UltrasonografíaRESUMEN
Vascular access infection is a frequent complication in hemodialysis patients. We report the second case worldwide of a prosthetic hemodialysis vascular graft infection by Coxiella burnetii, with intense hypermetabolism on PET-CT, Q fever serology consistent with persistent infection, and positive C. burnetii DNA in the blood and removed vascular graft.
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Coxiella burnetii/aislamiento & purificación , Infecciones Relacionadas con Prótesis/diagnóstico , Fiebre Q/diagnóstico , Diálisis Renal/efectos adversos , Injerto Vascular/efectos adversos , ADN Bacteriano/sangre , Femenino , Francia , Humanos , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Infecciones Relacionadas con Prótesis/microbiología , Fiebre Q/microbiología , Resultado del TratamientoRESUMEN
BACKGROUND: The main reason for anemia in renal failure patients is the insufficient erythropoietin production by the kidneys. Beside erythropoietin deficiency, in vitro studies have incriminated uremic toxins in the pathophysiology of anemia but clinical data are sparse. In order to assess if indole 3-acetic acid (IAA), indoxyl sulfate (IS), and paracresyl sulfate (PCS) -three protein bound uremic toxins- are clinically implicated in end-stage renal disease anemia we studied the correlation between IAA, IS and PCS plasmatic concentrations with hemoglobin and Erythropoietin Stimulating Agents (ESA) use in hemodialysis patients. METHODS: Between June and July 2014, we conducted an observational cross sectional study in two hemodialysis center. Three statistical approaches were conducted. First, we compared patients treated with ESA and those not treated. Second, we performed linear regression models between IAA, IS, and PCS plasma concentrations and hemoglobin, the ESA dose over hemoglobin ratio (ESA/Hemoglobin) or the ESA resistance index (ERI). Third, we used a polytomous logistic regression model to compare groups of patients with no/low/high ESA dose and low/high hemoglobin statuses. RESULTS: Overall, 240 patients were included in the study. Mean age ± SD was 67.6 ± 16.0 years, 55.4% were men and 42.5% had diabetes mellitus. When compared with ESA treated patients, patients with no ESA had higher hemoglobin (mean 11.4 ± 1.1 versus 10.6 ± 1.2 g/dL; p <0.001), higher transferrin saturation (TSAT, 31.1 ± 16.3% versus 23.1 ± 11.5%; p < 0.001), less frequently an IV iron prescription (52.1 versus 65.7%, p = 0.04) and were more frequently treated with hemodiafiltration (53.5 versus 36.7%). In univariate analysis, IAA, IS or PCS plasma concentrations did not differ between the two groups. In the linear model, IAA plasma concentration was not associated with hemoglobin, but was negatively associated with ESA/Hb (p = 0.02; R = 0.18) and with the ERI (p = 0.03; R = 0.17). IS was associated with none of the three anemia parameters. PCS was positively associated with hemoglobin (p = 0.03; R = 0.14), but negatively with ESA/Hb (p = 0.03; R = 0.17) and the ERI (p = 0.02; R = 0.19). In multivariate analysis, the association of IAA concentration with ESA/Hb or ERI was not statistically significant, neither was the association of PCS with ESA/Hb or ERI. Identically, in the subgroup of 76 patients with no inflammation (CRP <5 mg/L) and no iron deficiency (TSAT >20%) linear regression between IAA, IS or PCS and any anemia parameter did not reach significance. In the third model, univariate analysis showed no intergroup significant differences for IAA and IS. Regarding PCS, the Low Hb/High ESA group had lower concentrations. However, when we compared PCS with the other significant characteristics of the five groups to the Low Hb/high ESA (our reference group), the polytomous logistic regression model didn't show any significant difference for PCS. CONCLUSIONS: In our study, using three different statistical models, we were unable to show any correlation between IAA, IS and PCS plasmatic concentrations and any anemia parameter in hemodialysis patients. Indolic uremic toxins and PCS have no or a very low effect on anemia parameters.
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Anemia/sangre , Anemia/diagnóstico , Indicán/sangre , Ácidos Indolacéticos/sangre , Diálisis Renal/tendencias , Insuficiencia Renal Crónica/sangre , Anciano , Anciano de 80 o más Años , Anemia/etiología , Biomarcadores/sangre , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diálisis Renal/efectos adversos , Insuficiencia Renal Crónica/terapia , SulfatosRESUMEN
Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs). The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR) of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK) cells as innate immune effectors of antibody-dependent cellular cytotoxicity (ADCC), but few studies have investigated their alloreactive potential in the context of solid organ transplantation. Our study aimed to investigate the potential contribution of the antibody-dependent alloreactive function of NK cells to kidney graft dysfunction. We first conducted an observational study to investigate whether the cytotoxic function of NK cells is associated with chronic allograft dysfunction. The NK-Cellular Humoral Activation Test (NK-CHAT) was designed to evaluate the recipient and antibody-dependent reactivity of NK cells against allogeneic target cells. The release of CD107a/Lamp1(+) cytotoxic granules, resulting from the recognition of rituximab-coated B cells by NK cells, was analyzed in 148 kidney transplant recipients (KTRs, mean graft duration: 6.2 years). Enhanced ADCC responsiveness was associated with reduced graft function and identified as an independent risk factor predicting a decline in the estimated glomerular filtration rate over a 1-year period (hazard ratio: 2.83). In a second approach, we used the NK-CHAT to reveal the cytotoxic potential of circulating alloantibodies in vitro. The level of CD16 engagement resulting from the in vitro recognition of serum-coated allogeneic B cells or splenic cells was further identified as a specific marker of DSA-induced ADCC. The NK-CHAT scoring of sera obtained from 40 patients at the time of transplant biopsy was associated with ABMR diagnosis. Our findings indicate that despite the administration of immunosuppressive treatments, robust ADCC responsiveness can be maintained in some KTRs. Because it evaluates both the Fab recognition of alloantigens and Fc-driven NK cell activation, the NK-CHAT represents a potentially valuable tool for the non-invasive and individualized evaluation of humoral risk during transplantation.
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BACKGROUND: Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. Oxidative stress seems to play a pivotal role in this process, and purine metabolism may be involved in CKD-related oxidative stress. Xanthine oxidase (XO) is an enzyme involved in purine metabolism and is also responsible for the production of reactive oxygen species. METHODS: This prospective study aimed to analyze the relation between plasma dosages of molecules involved in redox balance, purine metabolism and cardiovascular events in patients with non-diabetic CKD stages 3-5 or on chronic hemodialysis (HD). CKD (n = 51) and HD (n = 50) patients were compared to matched healthy controls (n = 38) and followed-up for 3 years. RESULTS: Both CKD and HD patients had decreased plasma levels of antioxidants (selenium, zinc, vitamin C). HD patients had decreased levels of the antioxidant enzyme superoxide dismutase and increased levels of oxidation products (ischemia-modified albumin, malondialdehyde [MDA]). The following substrates and enzymes involved in purine metabolism were increased in the HD cohort: adenosine, adenosine deaminase and the pro-oxidant XO. XO activity was negatively correlated with super oxide dismutase and positively with MDA. Interestingly, XO activity was an independent predictor of cardiovascular events in CKD and HD patients, regardless of uric acid levels. Uric acid was not predictive of events. CONCLUSION: This highlights a possible role of XO itself in CKD-related cardiovascular disease (CVD) and raises the hypothesis that beneficial effects observed with XO inhibitors on CVD in CKD may also be due to the reduction of oxidative stress.
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Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/complicaciones , Ácido Úrico/sangre , Xantina Oxidasa/sangre , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Estrés Oxidativo , Valor Predictivo de las Pruebas , Estudios Prospectivos , Purinas/metabolismo , Diálisis Renal , Insuficiencia Renal Crónica/mortalidad , Factores de RiesgoRESUMEN
BACKGROUND: Immunization against hepatitis B virus (HBV) in kidney transplantation (KT) candidates and recipients is recommended. If anti-HBV surface antigen antibody (anti-HBsAb) titer of 10 IU/L is admitted to be protective, the optimal threshold, at and after KT, is unknown. In addition, the natural evolution of anti-HBsAb titers after KT is not reported. OBJECTIVES: To describe rates of protective immunity to HBV at time of KT (baseline) and evolution of anti-HBsAb titers during the following year. STUDY DESIGN: We retrospectively analyzed HBV serology at baseline, 15 days, and 4 and 12 months post-KT. No patient received vaccination during the study period, but information about previous vaccination was unavailable. RESULTS: At baseline 80% of 141 recipients had anti-HBsAb titer ≥10 IU/L. Among these 113 patients, 84 had subsequent HBV serologies at day 15 and month 4, and 67 had also serology at month 12. At month 12, 25% of patients had lost protective anti-HBsAb titers (p<0.001). The duration of protective anti-HBsAb titers was significantly longer when the initial titer was ≥ 100 IU/L versus <100 IU/L (log-rank test p<0.0001). Protective titers at month 12 persisted in 93% of patients with initial titer ≥100 IU/L compared to 33% with 10-100IU/L titer (p<0.0001). In contrast, duration of protective titers did not differ according to the anti-HBV core antigen antibody status at baseline. CONCLUSIONS: Despite a high prevalence of protective anti-HBsAb titer at KT, the loss of protective immunity during the following year was considerable, particularly when initial anti-HBsAb titer was <100 IU/L.
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Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Trasplante de Riñón , Adulto , Anciano , Femenino , Hepatitis B/inmunología , Hepatitis B/prevención & control , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Antiphospholipid antibodies (APL) are a heterogeneous family of auto-antibodies that recognize phospholipoproteins bound antigenic epitopes. APL prevalence in patients on chronic hemodialysis ranges from 11 to 37% in the literature. The association of APL with hemodialysis vascular access (VA) thrombosis has already been reported in small studies. In this single center and retrospective study, we defined the APL prevalence and APL risk factors in a large cohort of 192 hemodialysis patients. The association between history of VA thrombosis and APL presence was also analyzed. At least one type of APL was found in 38 patients (19.8%) of which 74% (n=28) had only lupus anticoagulant. Median age of APL positive patients was 68.1years vs. 71.3years in APL negative patients (P=0.02). Smoking history was associated with APL presence: 35.5% of APL positive patients had a smoking history vs only 18.3% of APL negative patients (P=0.04). The multivariate analysis showed an association between the history of VA thrombosis and patient age (HR [IC 95%]=1.04 [1.02-1.06]; P=0.001) or APL presence (HR [IC 95%]=3.03 [1.69-4.42]; P<10(-3)). In conclusion, the prevalence of APL in hemodialysis patients remains high despite hemodialysis techniques improvement: hemodiafiltration, biocompatibility improvements, ultrapure dialysis water. We report that a younger age and past history of smoking are associated with an increased risk of APL presence. The presence of APL, especially lupus anticoagulant, is associated to VA thrombosis in hemodialysis patients.
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Anticuerpos Antifosfolípidos/sangre , Derivación Arteriovenosa Quirúrgica/efectos adversos , Diálisis Renal , Trombosis/etiología , Anciano , Femenino , Humanos , Masculino , Estudios Retrospectivos , Fumar/efectos adversosRESUMEN
BACKGROUND: Pericardial effusion in uremic patients (UPE) was first described by R. Bright in 1836. It is generally agreed that patients require emergency pericardial drainage when tamponade signs are present, but in patients with no tamponade the optimal timing for drainage remains unclear. METHODS: To define patients who will require pericardial drainage, we retrospectively studied risk factors for pericardial drainage in patients admitted with pericardial effusion and chronic renal failure. RESULTS: Between 2000 and 2012, 44 UPE patients were identified using the database of our institution: 43% were under hemodialysis, 7% under peritoneal dialysis, 11% transplanted, 39% had chronic kidney disease (CKD) stage 4 or 5. Cause of UPE was uremic pericarditis in 45.5%, dialysis pericarditis in 45.5%, and other in 9%. On initial echocardiography, UPE was estimated small (<300 ml) in 38%, moderate (300-500 ml) in 32%, and large (>500 ml) in 30%. Tamponade signs were observed in 16% of patients. During follow-up, 100 % of large effusions required drainage (70% immediate, 30% delayed). For moderate and small UPE, the initial size on echocardiography was not discriminating. Serum albumin level was highly predictive of the risk of drainage: when albuminemia was ≤31 g/l, 35% patients were drained vs. only 7% when albuminemia was >31 g/l. CONCLUSION: In this first study reporting UPE drainage risk factors, all large UPE required drainage even when extra-renal epuration intensification or medical treatment were tried. This suggests that large UPE should be drained without delay. For small and moderate UPE, size of effusion on echocardiography does not predict drainage requirement but serum albumin level does.
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Drenaje , Derrame Pericárdico/sangre , Derrame Pericárdico/cirugía , Pericarditis/sangre , Albúmina Sérica/metabolismo , Uremia/sangre , Adulto , Anciano , Ecocardiografía , Femenino , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Derrame Pericárdico/diagnóstico por imagen , Derrame Pericárdico/etiología , Pericarditis/complicaciones , Valor Predictivo de las Pruebas , Diálisis Renal/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Uremia/complicacionesRESUMEN
OBJECTIVE: The role of interferon-α (IFNα) in the pathogenesis of systemic lupus erythematosus (SLE) is strongly supported by gene expression studies. The aim of this study was to improve characterization of the blood IFN signature in adult SLE patients. METHODS: Consecutive patients were enrolled and followed up prospectively. Microarray data were generated using Illumina BeadChips. A modular transcriptional repertoire was used as a framework for the analysis. RESULTS: Our repertoire of 260 modules, which consisted of coclustered gene sets, included 3 IFN-annotated modules (M1.2, M3.4, and M5.12) that were strongly up-regulated in SLE patients. A modular IFN signature was observed in 54 of 62 patients (87%) or 131 of all 157 samples (83%). The IFN signature was more complex than expected, with each module displaying a distinct activation threshold (M1.2 < M3.4 < M5.12), thus providing a modular score by which to stratify SLE patients based on the presence of 0, 1, 2, or 3 active IFN modules. A similar gradient in modular IFN signature was observed within patients with clinically quiescent disease, for whom moderate/strong modular scores (2 or 3 active IFN modules) were associated with higher anti-double-stranded DNA titers and lower lymphocyte counts than those in patients with absent/mild modular scores (0 or 1 active IFN modules). Longitudinal analyses revealed both stable (M1.2) and variable (M3.4 and M5.12) components of modular IFN signature over time in single patients. Interestingly, mining of other data sets suggested that M3.4 and M5.12 could also be driven by IFNß and IFNγ. CONCLUSION: Modular repertoire analysis reveals complex IFN signatures in SLE, which are not restricted to the previous IFNα signature, but which also involve IFNß and IFNγ.
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Perfilación de la Expresión Génica/métodos , Interferón Tipo I/genética , Interferón gamma/genética , Lupus Eritematoso Sistémico/genética , Adolescente , Adulto , Anciano , Biomarcadores/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Interferón Tipo I/metabolismo , Interferón-alfa/genética , Interferón-alfa/metabolismo , Interferón beta/genética , Interferón beta/metabolismo , Interferón gamma/metabolismo , Lupus Eritematoso Sistémico/metabolismo , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: About 1% of patients admitted to the Emergency Department (ED) have hypernatremia, a condition associated with a mortality rate of 20 to 60%. Management recommendations originate from intensive care unit studies, in which patients and medical diseases differ from those in ED. METHODS: We retrospectively studied clinical characteristics, treatments, and outcomes of severely hypernatremic patients in the ED and risk factors associated with death occurrence during hospitalization. RESULTS: During 2010, 85 cases of severe hypernatremia ≥ 150 mmol/l were admitted to ED. Hypernatremia occurred in frail patients: mean age 79.7 years, 55% institutionalized, 28% with dementia.Twenty four percent of patients died during hospitalization. Male gender and low mean blood pressure (MBP) were independently associated with death, as well as slow natremia correction speed, but not the severity of hyperosmolarity at admission. Infusion solute was inappropriate for 45% of patients with MBP <70 mmHg who received hypotonic solutes and 22% of patients with MBP ≥ 70 mmHg who received isotonic solutes or were not perfused. CONCLUSIONS: This is the first study assessing outcome of hypernatremic patients in the ED according to the treatment provided. It appears that not only a too quick, but also a too slow correction speed is associated with an increased risk of death regardless of initial natremia. Medical management of hypernatremic patients must be improved regarding evaluation and treatment.
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Fluidoterapia/métodos , Fluidoterapia/estadística & datos numéricos , Hipernatremia/mortalidad , Hipernatremia/terapia , Anciano , Anciano de 80 o más Años , Femenino , Francia/epidemiología , Humanos , Hipernatremia/diagnóstico , Incidencia , Masculino , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Controlling alloimmune humoral response is a challenge in transplantation. Few studies have evaluated the impact of maintenance immunosuppression on blood humoral parameters. MATERIAL/METHODS: We performed a post-hoc analysis on 307 kidney transplant recipients included in a prospective randomized trial comparing tacrolimus/mycophenolate mofetil (Tac/MMF) vs. cyclosporine/azathioprine (CsA/AZA), both used with antithymocyte globulin induction and steroids. Humoral parameters were analyzed at D0, D15, and M12. RESULTS: IgG, IgA, and IgM levels decreased significantly as soon as D15 in both groups (35%, 26%, and 35% respectively, vs. D0). At M12, although peripheral B-cell counts did not differ between the groups, Tac/MMF regimen was associated with lower IgG, IgA, and IgM levels than CsA/AZA (5.9%, 14.6%, and 34%, respectively). Hypogammaglobulinemia at D15 was not associated with an increased risk of infections during the first year. The proportion of HLA-sensitized patients decreased in the Tac/MMF group (15.9% at D0 and 6.7% at M12, p=0.02) and remained stable in the CsA/AZA group (10.3% at D0 and 8.9% at M12, p=0.5). More patients sensitized at baseline became non-sensitized at M12 with Tac/MMF than with CsA/AZA. CONCLUSIONS: Our results suggest humoral immunosuppression is better with Tac/MMF than with CsA/AZA during the first year of kidney transplantation.
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Supervivencia de Injerto/efectos de los fármacos , Inmunidad Humoral/efectos de los fármacos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/métodos , Azatioprina/farmacología , Azatioprina/uso terapéutico , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Ciclosporina/farmacología , Ciclosporina/uso terapéutico , Quimioterapia Combinada , Femenino , Supervivencia de Injerto/inmunología , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Inmunosupresores/farmacología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/farmacología , Ácido Micofenólico/uso terapéutico , Estudios Prospectivos , Tacrolimus/farmacología , Tacrolimus/uso terapéutico , Resultado del TratamientoAsunto(s)
Amiloidosis/etiología , Cabeza Femoral/lesiones , Fracturas Espontáneas/etiología , Fracturas de Cadera/etiología , Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , Microglobulina beta-2/análisis , Anciano , Amiloidosis/diagnóstico , Amiloidosis/metabolismo , Biomarcadores/análisis , Biopsia , Cabeza Femoral/química , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/cirugía , Fracturas Espontáneas/diagnóstico por imagen , Fracturas Espontáneas/metabolismo , Fracturas Espontáneas/cirugía , Hemiartroplastia , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/metabolismo , Fracturas de Cadera/cirugía , Humanos , Inmunohistoquímica , Fallo Renal Crónico/complicaciones , Masculino , RadiografíaRESUMEN
Hepatitis E virus (HEV) is an emerging cause of acute and chronic hepatitis in Europe, particularly in solid organ transplant recipients. Anti-HEV IgG/IgM testing in kidney transplant recipients with liver biological disturbances indicated high HEV exposure in our geographical area and led to diagnose HEV infection in 6% of cases.
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Virus de la Hepatitis E/aislamiento & purificación , Hepatitis E/diagnóstico , Trasplante de Riñón/efectos adversos , Anticuerpos Antivirales/sangre , Francia/epidemiología , Hepatitis E/epidemiología , Hepatitis E/virología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Hígado/enzimología , Hepatopatías/fisiopatología , ARN Viral/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SerologíaRESUMEN
Hepatitis E virus (HEV) is an emerging cause of acute hepatitis in Europe, particularly in southern France, and HEV is a new causative agent of chronic hepatitis and cirrhosis in immunocompromised patients. However, the data regarding HEV infection after kidney transplantation are still scarce with respect to the clinical issues that have been raised, and no study has specifically focused on kidney transplant recipients. This study described the clinical features and outcomes of HEV infections in a cohort of kidney transplant recipients living in southeastern France. The epidemiological, clinical, and virological characteristics of HEV infections diagnosed by PCR over a 53-month period were retrospectively analyzed in a cohort of 1,350 kidney transplant recipients monitored at the Marseille University Hospital. Sixteen HEV infections were diagnosed, all of which were autochthonous and involved genotype 3 viruses (HEV-3). Chronic infections occurred in 80% of these patients and resolved in half of the cases after a median time of 39 months. The rate of HEV clearance was 54% after a decrease in the dose of immunosuppressants. One patient developed liver cirrhosis 14 months after infection and experienced acute rejection after a decrease in the dose of immunosuppressants. Autochthonous HEV-3 infections in kidney transplant recipients progress to chronicity in most cases and might be complicated by early liver cirrhosis. Chronic HEV infection can resolve following the reduction of immunosuppressive therapy, but ribavirin may be required if reduction of the immunosuppressant dose is not associated with HEV clearance or is inappropriate for the patient management.
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Virus de la Hepatitis E/aislamiento & purificación , Hepatitis E/epidemiología , Hepatitis E/patología , Trasplante de Riñón/efectos adversos , Adulto , Anciano , Enfermedad Crónica/epidemiología , Estudios de Cohortes , Femenino , Francia/epidemiología , Genotipo , Hepatitis E/virología , Virus de la Hepatitis E/clasificación , Virus de la Hepatitis E/genética , Humanos , Huésped Inmunocomprometido , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estudios Retrospectivos , TrasplanteRESUMEN
BACKGROUND: Hepatitis E virus (HEV) is a new causative agent of chronic hepatitis in solid organ transplant recipients. Clinical studies suggest that the occurrence and persistence of chronic HEV infection are related to the immunological status of patients. METHODS: We used whole-genome microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to compare the transcriptional profiles of whole blood from 8 kidney transplant recipients with chronic HEV infection and 8 matched kidney transplant recipients without HEV infection. RESULTS: We found that 30 genes in HEV-infected patients were upregulated, compared with those in control patients, as determined by microarray analysis. In contrast, no genes were downregulated. The 30 upregulated genes included 25 interferon-stimulated genes. Increased expression of the genes that encode IFIT1, IFI44L, RSAD2, EPSTI1, and ISG15 was confirmed by qRT-PCR. Interestingly, the expression levels of these genes were associated with the persistence of HEV infection. CONCLUSIONS: Increased expression of interferon-stimulated genes may favor the persistence of an HEV infection. Whether the expression of interferon-stimulated genes is a marker of ongoing viremia or independent prognostic marker of HEV clearance needs further investigations. CLINICAL TRIALS REGISTRATION: NCT01090232.
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Virus de la Hepatitis E/inmunología , Hepatitis E/inmunología , Hepatitis Crónica/inmunología , Interferones/genética , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Francia/epidemiología , Perfilación de la Expresión Génica , Regulación Viral de la Expresión Génica , Anticuerpos Antihepatitis/sangre , Hepatitis E/epidemiología , Hepatitis E/genética , Hepatitis E/virología , Virus de la Hepatitis E/genética , Hepatitis Crónica/epidemiología , Hepatitis Crónica/genética , Hepatitis Crónica/virología , Humanos , Interferones/inmunología , Trasplante de Riñón/inmunología , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Complicaciones Posoperatorias/inmunología , Complicaciones Posoperatorias/virología , Estudios Prospectivos , ARN Viral/sangre , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia ArribaRESUMEN
INTRODUCTION: Henoch-Schönlein purpura is a small-vessel systemic vasculitis. Although its exact pathophysiology remains unknown, Henoch-Schönlein purpura has been reported in association with various medical conditions including hypersensitivity. We report the case of a patient with vancomycin-induced Henoch-Schönlein purpura. CASE PRESENTATION: A 42-year-old Caucasian man who had previously undergone a heart transplant was diagnosed as having an intra-abdominal abscess after he underwent a Hartmann procedure. At 15 days after initiation of antibiotic therapy including vancomycin, he developed a purpuric rash of the lower limbs, arthralgia, and macroscopic hematuria. At that time, our patient was already on hemodialysis for end-stage renal disease. Henoch-Schönlein purpura was diagnosed. After a second 15-day course of vancomycin, a second flare of Henoch-Schönlein purpura occurred. Skin biopsies showed leucocytoclastic vasculitis with IgA deposits and eosinophils in the peri-capillary inflammatory infiltrate, suggesting an allergic mechanism. After vancomycin was stopped, we did not observe any further flares. Only five cases of isolated cutaneous vasculitis, one case of lupus-like syndrome and one case of Henoch-Schönlein purpura after vancomycin treatment have been described to date in the literature. CONCLUSIONS: Clinicians should be aware that systemic vasculitis can be induced by some treatments. Vancomycin is a widely prescribed antibiotic. Occurrence of rare but serious Henoch-Schönlein purpura associated with vancomycin requires its prompt discontinuation.
RESUMEN
INTRODUCTION: Legionnaires' disease is recognized as a multi-systemic illness. Afflicted patients may have pulmonary, renal, gastrointestinal tract and central nervous system complications. However, renal insufficiency is uncommon. The spectrum of renal involvement may range from a mild and transient elevation of serum creatinine levels to anuric renal failure requiring dialysis and may be linked to several causes. In our present case report, we would like to draw attention to the importance of the pathological documentation of acute renal failure by reporting a case of a patient with acute tubulointerstitial nephritis complicating Legionnaires' disease. CASE PRESENTATION: A 55-year-old Caucasian man was admitted to our hospital for community-acquired pneumonia complicated by acute renal failure. Legionella pneumophila serogroup type 1 was diagnosed. Although the patient's respiratory illness responded to intravenous erythromycin and ofloxacin therapy, his renal failure worsened, he became anuric, and hemodialysis was started. A renal biopsy was performed, which revealed severe tubulointerstitial nephritis. After initiation of steroid therapy, his renal function improved dramatically. CONCLUSIONS: This case highlights the importance of kidney biopsies in cases where acute renal failure is a complicating factor in Legionnaires' disease. If the presence of acute tubulointerstitial nephritis can be confirmed, it will likely respond favorably to steroidal treatment and thus irreversible renal damage and chronic renal failure will be avoided.