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BACKGROUND: Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular events and bleeding. Optimizing risk assessment of ESKD patients regarding the risk of thromboembolism and bleeding complications in comorbid conditions, including atrial fibrillation and coronary heart disease, is challenging. To improve risk prediction we investigated growth differentiation factor-15 (GDF-15), a promising cardiovascular biomarker, and its relation to adverse outcomes. METHODS: In this prospective, multicentre, population-based cohort study, GDF-15 was measured in 594 ESKD patients on haemodialysis (median age 66 years, 38% female), who were followed up for a median of 3.5 years. The association of GDF-15 with major bleeding, arterial thromboembolism, major adverse cardiac events (MACE) and death was analysed within a competing risk framework. Further, we evaluated the additive predictive value of GDF-15 to cardiovascular and death risk assessment. RESULTS: GDF-15 levels were in median 5475 ng/l (25th-75th percentile 3964-7533) and independently associated with major bleeding {subdistribution hazard ratio [SHR] 1.31 per double increase [95% confidence interval (CI) 1.00-1.71]}, MACE [SHR 1.47 (95% CI 1.11-1.94)] and all-cause mortality [SHR 1.58 (95% CI 1.28-1.95)] but not arterial thromboembolism [SHR 0.91 (95% CI 0.61-1.36)]. The addition of GDF-15 to the HAS-BLED score significantly improved discrimination and calibration for predicting major bleeding [C-statistics increased from 0.61 (95% CI 0.52-0.70) to 0.68 (95% CI 0.61-0.78)]. Furthermore, we established an additive predictive value of GDF-15 beyond current risk models for predicting MACE and death. CONCLUSION: GDF-15 predicts the risk of major bleeding, cardiovascular events and death in ESKD patients on haemodialysis and might be a valuable marker to guide treatment decisions in this challenging patient population.
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Fallo Renal Crónico , Tromboembolia , Humanos , Femenino , Anciano , Masculino , Estudios de Cohortes , Estudios Prospectivos , Factor 15 de Diferenciación de Crecimiento , Hemorragia/etiología , Hemorragia/epidemiología , Medición de Riesgo , Biomarcadores , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , Factores de RiesgoRESUMEN
BACKGROUND: Patients with end-stage kidney disease on haemodialysis suffer from frequent complications requiring hospitalisation. Atrial fibrillation is a burdensome comorbidity amongst patients on haemodialysis. We aimed to assess frequency, reasons, and duration of hospitalisations in haemodialysis patients and their association with atrial fibrillation and anticoagulation. METHODS: Prevalent patients with end-stage kidney disease on haemodialysis were recruited into a prospective cohort study and observed for a median observation time of 3.4 years. Hospitalisations were recorded from discharge letters, medical records, and patient interviews. The association of atrial fibrillation, anticoagulation, and time-in-therapeutic range of vitamin K antagonist treatment with hospitalisations was analysed using negative binomial regression. RESULTS: Out of 625 patients, 238 (38.1%) had atrial fibrillation. Median number of hospitalisations per patient was 3.0 (1.0-5.0). Incidence rate of hospitalisation was 1.7 per patient-year in all and 1.9 in atrial fibrillation patients, median duration per hospitalisation was 7.9 (4.8-12.9) and 8.8 (5.7-13.3) days, respectively. Most frequent reasons for hospitalisation were vascular access complication/intervention (11.7%) and infection/fever (11.4%), while bleeding events comprised 6.0% of all hospitalisations. Atrial fibrillation patients had 27% higher risk of hospitalisation than patients without atrial fibrillation (incidence rate ratio [IRR] 1.27, 95% confidence interval [CI] 1.10-1.47). In atrial fibrillation patients, anticoagulation (enoxaparin or phenprocoumon, 41.6% of AF patients) was associated with increased risk of all-cause (IRR 1.38, 95%CI 1.14-1.69) and bleeding-related hospitalisation (IRR 1.96, 95%CI 1.06-3.63). There was no association between anticoagulation and stroke-related hospitalisation. In atrial fibrillation patients on phenprocoumon, increasing time-in-therapeutic range was associated with decreased risk of all-cause (IRR 0.35, 95%CI 0.14-0.87), but not bleeding-related hospitalisation (IRR 0.13, 95%CI 0.01-1.38). CONCLUSION: In haemodialysis patients, presence of atrial fibrillation and, among those with atrial fibrillation, anticoagulation were associated with higher risk of all-cause hospitalisation, including bleeding-related hospitalisation in the latter. Increasing time-in-therapeutic range in patients on vitamin K antagonist treatment was associated with decreased risk of all-cause, but not bleeding-related hospitalisation.
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Coronavirus disease 2019 (COVID-19)-induced metabolic alterations have been proposed as a source for prognostic biomarkers and may harbor potential for therapeutic exploitation. However, the metabolic impact of COVID-19 in hemodialysis (HD), a setting of profound a priori alterations, remains unstudied. To evaluate potential COVID-19 biomarkers in end-stage kidney disease (CKD G5), we analyzed the plasma metabolites in different COVID-19 stages in patients with or without HD. We recruited 18 and 9 asymptomatic and mild, 11 and 11 moderate, 2 and 13 severely affected, and 10 and 6 uninfected HD and non-HD patients, respectively. Plasma samples were taken at the time of diagnosis and/or upon admission to the hospital and analyzed by targeted metabolomics and cytokine/chemokine profiling. Targeted metabolomics confirmed stage-dependent alterations of the metabolome in non-HD patients with COVID-19, which were less pronounced in HD patients. Elevated kynurenine levels and lipid dysregulation, shown by an increase in circulating free fatty acids and a decrease in lysophospholipids, could distinguish patients with moderate COVID-19 from non-infected individuals in both groups. Kynurenine and lipid alterations were also associated with ICAM-1 and IL-15 levels in HD and non-HD patients. Our findings support the kynurenine pathway and plasma lipids as universal biomarkers of moderate and severe COVID-19 independent of kidney function.
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COVID-19 , Quinurenina , Humanos , Triptófano , Diálisis Renal , LípidosRESUMEN
The safety and efficacy of sodium-glucose cotransporter 2 inhibitors in posttransplantation diabetes mellitus is unknown. We converted stable kidney transplant patients to 10 mg empagliflozin, aiming at replacing their insulin therapy (<40 IU/d). N = 14 participants (the required sample size) completed the study visits through 4 weeks and N = 8 through 12 months. Oral glucose tolerance test (OGTT)-derived 2-hour glucose (primary end point) increased from 232 ± 82 mg/dL (baseline) to 273 ± 116 mg/dL (4 weeks, P = .06) and to 251 ± 71 mg/dL (12 months, P = .41). Self-monitored blood glucose and hemoglobin A1c were also clinically inferior with empagliflozin monotherapy, such that insulin was reinstituted in 3 of 8 remaining participants. Five participants (2 of them dropouts) vs nine of 24 matched reference patients developed bacterial urinary tract infections (P = .81). In empagliflozin-treated participants, oral glucose insulin sensitivity decreased and beta-cell glucose sensitivity increased at the 4-week and 12-month OGTTs. Estimated glomerular filtration rate and bioimpedance spectroscopy-derived extracellular and total body fluid volumes decreased by 4 weeks, but recovered. All participants lost body weight. No participant developed ketoacidosis; 1 patient developed balanitis. In conclusion, although limited by sample size and therefore preliminary, these results suggest that empagliflozin can safely be used as add-on therapy, if posttransplant diabetes patients are monitored closely (NCT03113110).
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Compuestos de Bencidrilo/uso terapéutico , Glucemia/metabolismo , Líquidos Corporales/metabolismo , Diabetes Mellitus Tipo 2/terapia , Glucósidos/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Trasplante de Islotes Pancreáticos/efectos adversos , Complicaciones Posoperatorias/tratamiento farmacológico , Composición Corporal , Intervención Médica Temprana , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Rechazo de Injerto/metabolismo , Supervivencia de Injerto , Humanos , Insulina/metabolismo , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Proyectos Piloto , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/metabolismo , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéuticoRESUMEN
BACKGROUND: Despite a higher prevalence of chronic kidney disease among women, more men than women start renal replacement therapy (RRT). We hypothesized that gender differences in health care access exist and therefore aimed at determining whether characteristics and outcomes of haemodialysis patients over time differ by sex. METHODS: We studied all 28 323 adults who began haemodialysis during 1965-2014 in the Austrian Dialysis Registry, analysing trends in patient characteristics by sex and decade with mortality (via Cox regression), which was compared with the mortality of the Austrian general population. RESULTS: More men than women started haemodialysis (60.1% men versus 39.9% women overall), with minor differences among decades and age groups. The male:female mortality rate ratio in the general population ranged from 1.2 to 2.4 for age groups >18 years and in haemodialysis patients ranged from 0.80 to 1.3 (closer to 1 than in the general population, but consistently >1 in Decades 3-5). In recent decades, diabetes and hypertension replaced glomerulonephritis as the primary cause of end-stage renal disease in both men and women. Interaction analyses showed the mortality risk associated with haemodialysis access (only recorded in Decade 5) was significantly lower for men than for women. CONCLUSIONS: The male:female mortality rate ratio and the proportion of women starting haemodialysis were remarkably stable, which does not support the hypothesis of gender differences in health care/haemodialysis access or could imply that such differences might have persisted over decades. Future research should expand to other countries and other forms of RRT.
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Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Diálisis Renal/mortalidad , Diálisis Renal/métodos , Terapia de Reemplazo Renal/mortalidad , Terapia de Reemplazo Renal/métodos , Adulto , Anciano , Austria/epidemiología , Femenino , Glomerulonefritis/terapia , Humanos , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Prevalencia , Sistema de Registros , Factores Sexuales , Factores de Tiempo , Adulto JovenRESUMEN
Despite increasing evidence in favor of prophylactic valganciclovir treatment in kidney transplant recipients for the prevention of cytomegalovirus (CMV) infection, the impact of preemptive vs. prophylactic treatment on long-term clinical outcomes is unclear. In this retrospective study, 187 kidney transplant recipients with serologic intermediate-risk constellation (recipient CMV IgG positive) received either preemptive or prophylactic treatment with valganciclovir. Patient survival (primary endpoint), graft survival, viremia rates, and other CMV-related outcomes were analyzed. Prophylactic therapy reduced the rates for CMV viremia during the first year (hazard ratio: 0.48, 95% confidence interval [CI] 0.30-0.75; p < 0.001). There was a trend for higher three-yr patient mortality in the prophylactic group (hazard ratio: 5.08, 95% CI 0.62-41.3; p = 0.091), and the rate of graft loss was not reduced (hazard ratio: 0.93, 95% CI 0.32-2.68; p = 0.894). Estimated glomerular filtration rate over three yr was on average 6.8 mL/min/1.73 m(2) lower in the prophylactic group (95% CI -11.68 to -1.81; p = 0.007) using a multivariate random effects model but showed more improvement over time. Prophylactic valganciclovir treatment reduced the rate of CMV infections during the first year post-transplant but no effects of prophylactic treatment on patient and graft survival or kidney function over three yr were observed.
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Profilaxis Antibiótica , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/tratamiento farmacológico , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias , Citomegalovirus/patogenicidad , Infecciones por Citomegalovirus/epidemiología , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/etiología , Humanos , Fallo Renal Crónico/cirugía , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
No effective interventions to reduce risk for new-onset diabetes after transplantation (NODAT), a condition associated with postoperative hyperglycemia and reduced patient and graft survival, have been established. In this 1-year, proof-of-concept clinical trial, we randomly assigned 50 renal transplant recipients to immediate-postoperative isophane insulin for evening blood glucose ≥140 mg/dl (treatment group) or short-acting insulin and/or oral antidiabetic agents for blood glucose ≥180-250 mg/dl (standard-of-care control group). We included only patients without a history of diabetes who received tacrolimus. By the third postoperative evening, all patients in the treatment group had blood glucose ≥140 mg/dl and were subsequently treated with basal insulin; during the first 3 weeks after transplantation, the mean ± SD daily insulin dosage was 17±11 IU/d. Among controls, 23 (92%) of 25 had blood glucose ≥200 mg/dl and 18 (72%) of 25 received standard-of-care antihyperglycemic treatment. Asymptomatic hypoglycemia occurred five times in the treatment group and once in the control group. Throughout follow-up, the treatment group had 73% lower odds of NODAT (odds ratio, 0.27) than the control group, and hemoglobin A1c was on average 0.38% lower in the treatment group than the control group. Twelve months after transplantation, all patients in the treatment group were insulin-independent, whereas 7 (28%) of 25 controls required antidiabetic agents. The groups did not differ for insulin sensitivity, but the treatment group showed better ß-cell function throughout the 1-year follow-up. In conclusion, this study suggests regimens that include basal insulin significantly reduce the odds for NODAT after renal transplantation, presumably via insulin-mediated protection of ß cells.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/etiología , Hiperglucemia/prevención & control , Insulina/administración & dosificación , Trasplante de Riñón/efectos adversos , Adulto , Anciano , Glucemia/análisis , Intervalos de Confianza , Femenino , Estudios de Seguimiento , Humanos , Hiperglucemia/etiología , Hipoglucemiantes/administración & dosificación , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/cirugía , Trasplante de Riñón/métodos , Modelos Lineales , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Oportunidad Relativa , Cuidados Posoperatorios/métodos , Complicaciones Posoperatorias/prevención & control , Valor Predictivo de las Pruebas , Medición de Riesgo , Prevención Secundaria/métodos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Chronic kidney disease (CKD) drastically increases the risk for cardiovascular morbidity and mortality and its worldwide prevalence is still rising. Effective treatment slows CKD progression, prevents development of end-stage kidney disease and cardiovascular disease thereby prolonging survival of patients. Recently, several large-scale studies with sodium-glucose cotransport2 inhibitors (SGLT-2i) have demonstrated profound nephroprotective and cardioprotective properties in patients with type 2 diabetes mellitus with both CKD and heart failure. Recently, the dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial demonstrated that the selective SGLT-2i dapagliflozin reduced the hazard ratio for a composite renal and cardiovascular death endpoint in patients with CKD with or without type 2 diabetes. Furthermore, dapagliflozin exerted strong nephroprotection in CKD patients with diverse etiologies like IgA nephropathy. Furthermore, other promising CKD trials such as with empagliflozin are underway. Hence, individualized treatment with SGLT2i represents a promising therapeutic option for patients with both diabetic and non-diabetic CKD. Here we summarize the current knowledge on the treatment with SGLT-2i in CKD patients underscoring a strong rationale for SGLT2 inhibition to be incorporated into standard of care for most CKD patients also with non-diabetic kidney disease. Finally, we aim to translate the current evidence into recommendations for the clinical practice in the management of patients with CKD.
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Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , RiñónRESUMEN
Epidemiological investigations have shown that approximately 2-3% of all Austrians have diabetes mellitus with renal involvement, leaving 250,000 people in Austria affected. The risk of occurrence and progression of this disease can be attenuated by lifestyle interventions as well as optimization of blood pressure, blood glucose control and special drug classes. The present article represents the joint recommendations of the Austrian Diabetes Association and the Austrian Society of Nephrology for the diagnostic and treatment strategies of diabetic kidney disease.
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Diabetes Mellitus , Nefropatías Diabéticas , Nefrología , Humanos , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/terapia , Austria , Presión Sanguínea , Estilo de Vida , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Diabetes Mellitus/terapiaRESUMEN
BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by pathogenic autoantibodies, which can be removed by extracorporeal procedures. While previous studies have shown short-term efficacy of immunoadsorption (IAS) in SLE, no information on long-term benefit and safety is available. METHODS: IAS was offered to patients with highly active renal disease when conventional therapy had failed. Eleven patients entered the prolonged IAS programme and were followed for up to 10 years (mean 6.4 ± 3.5). Efficacy of IAS was determined by reduction in proteinuria (primary outcome), global disease activity [SLE Disease Activity Index (SLEDAI)] and anti-double-stranded DNA (anti-dsDNA) levels (secondary outcomes). Full/partial remission was defined as ≤ 0.5/≤ 1.0 g/day for proteinuria, ≤ 5/≤ 8 for SLEDAI and ≤ 25/≤ 50 IU/mL for anti-dsDNA levels. We further assessed flares, infections, malignancies and procedure-related adverse events. RESULTS: Short-term IAS (≤ 1 year) resulted in a significant reduction of proteinuria (9.2 ± 3.7 to 2.3 ± 2.4, P = 0.0001), disease activity (SLEDAI 19 ± 8 to 4 ± 2, P = 0.0004) and dsDNA levels (168 ± 205 to 45 ± 34, P = 0.001). In patients without remission after 1 year (n = 5), prolonged IAS decreased proteinuria from 4.3 ± 2.4 to 0.5 ± 0.4 g/day, P = 0.02. At the end of observation, complete remission in proteinuria was achieved in seven patients (64%) and partial remission in two (18%) additional patients. One patient flared and was discontinued; in all other patients, disease activity and anti-dsDNA stabilized at remission levels. Flares (0.28 ± 0.30) and infections (0.66 ± 0.70 per patient/year) were relatively uncommon; no malignancies, anaphylactic or orthostatic adverse events were observed. CONCLUSION: IAS is effective in short-term use but prolonged IAS can provide additional therapeutic benefit while showing an acceptable safety profile. The vast majority of initially therapy-refractory patients met the remission criteria at the end of observation.
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Técnicas de Inmunoadsorción , Nefritis Lúpica/inmunología , Nefritis Lúpica/terapia , Proteinuria/prevención & control , Adulto , Eliminación de Componentes Sanguíneos/métodos , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/uso terapéutico , Pruebas de Función Renal , Nefritis Lúpica/diagnóstico , Masculino , Estudios Prospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Patients with end-stage kidney disease (ESKD) on hemodialysis (HD) are at increased risk for bleeding. However, despite relevant clinical implications regarding dialysis modalities or anticoagulation, no bleeding risk assessment strategy has been established in this challenging population. METHODS: Analyses on bleeding risk assessment models were performed in the population-based Vienna InVestigation of Atrial fibrillation and thromboemboLism in patients on hemoDialysIs (VIVALDI) study including 625 patients. In this cohort study, patients were prospectively followed for a median observation period of 3.5 years for the occurrence of major bleeding. First, performances of existing bleeding risk scores (i.e., HAS-BLED, HEMORR2HAGES, ATRIA, and four others) were evaluated in terms of discrimination and calibration. Second, four machine learning-based prediction models that included clinical, dialysis-specific, and laboratory parameters were developed and tested using Monte Carlo cross-validation. RESULTS: Of 625 patients (median age: 66 years, 37% women), 89 (14.2%) developed major bleeding, with a 1-year, 2-year, and 3-year cumulative incidence of 6.1% (95% confidence interval [CI]: 4.2-8.0), 10.3% (95% CI: 8.0-12.8), and 13.5% (95% CI: 10.8-16.2), respectively. C-statistics of the seven contemporary bleeding risk scores ranged between 0.54 and 0.59 indicating poor discriminatory performance. The HAS-BLED score showed the highest C-statistic of 0.59 (95% CI: 0.53-0.66). Similarly, all four machine learning-based predictions models performed poorly in internal validation (C-statistics ranging from 0.49 to 0.55). CONCLUSION: Existing bleeding risk scores and a machine learning approach including common clinical parameters fail to assist in bleeding risk prediction of patients on HD. Therefore, new approaches, including novel biomarkers, to improve bleeding risk prediction in patients on HD are needed.
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Hemodialysis patients (HD) are expected to have excess mortality in coronavirus disease 2019 (COVID-19). This was challenged by a recent study reporting HD patients to have comparable mortality and less ICU admissions when hospitalized with COVID-19. An altered immune system due to chronic inflammation might protect HD-patients from severe COVID-19. Therefore, we aimed to describe the peripheral blood immune phenotype in HD-patients and respective controls with COVID-19. Methods: Sixty-four patients (31 HD, 33 non-HD) with PCR-confirmed COVID-19 and 16 control patients (10 HD, 6 non-HD) were prospectively included. According to symptoms, COVID-19 patients were categorized as asymptomatic/mild, moderate or severe COVID-19 phenotypes. Cytokine profiling and immune phenotyping was performed. Results: Th1 and Th17 plasma cytokine levels were highly increased in HD patients without COVID-19 and were not significantly regulated during COVID-19. In non-HD COVID-19 patients these cytokines increased significantly with disease severity. While all patients with moderate or severe COVID-19 showed hallmarks of COVID-19 such as decreased CD3+, CD4+ and CD8+ and CD4+CD25hiFoxP3+ regulatory T cells, significantly increased CD38+CD8+ effector memory and CD38+CD8+ TEMRA T cells were detected in moderate/severe COVID-19 HD patients, which was not observed in non-HD patients with moderate or severe COVID-19. Furthermore, CD161+CD8+ T cells decreased significantly in non-HD COVID-19 patients dependent on disease severity, but not in HD patients. Dynamics of B cells and subtypes were comparable in HD and non-HD COVID-19 patients. Conclusions: HD patients might be protected from severe COVID-19 due to their chronic inflammatory state with increased CD38+CD8+ effector memory and TEMRA T cells as well as CD161+CD8+ T cells.
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COVID-19/inmunología , Inflamación/inmunología , Diálisis Renal , SARS-CoV-2 , Linfocitos T/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Linfocitos B/inmunología , Citocinas/sangre , Femenino , Humanos , Inflamación/sangre , Masculino , Persona de Mediana Edad , Insuficiencia Renal CrónicaRESUMEN
BACKGROUND: Evidence supporting the use of anticoagulation for the prevention of stroke and thromboembolism in patients with kidney failure on hemodialysis (HD) and atrial fibrillation (AF) is limited. We prospectively assessed the incidences of stroke and major bleeding, as well as anticoagulation strategies in patients on HD with AF. METHODS: We recruited 625 prevalent HD patients into a population-based observational cohort study. The primary prospective outcomes were thromboembolic events (stroke, transient ischemic attack, systemic embolism) and major bleeding. Secondary outcomes included a composite of thromboembolic events, major bleeding, and cardiovascular death to determine net clinical harm. RESULTS: A total of 238 patients (38.1%) had AF, 165 (26.4%) already at baseline and 73 (15.9%) developed AF during a median follow up of 870 days. Forty (6.4%) thromboembolic events and 89 (14.2%) major bleedings occurred. Overall, 256 patients died (41.0%). In AF patients, use of vitamin K antagonists (VKAs) in 61 patients (25.6%) was not significantly associated with reduced risk of the primary thromboembolic outcome (subdistribution hazard ratio [SHR] 1.41 adjusted for age, sex, congestive heart failure, hypertension, stroke/transient ischemic attack/thromboembolism, vascular disease, and diabetes history score and antiplatelet co-medication (95% CI, 0.49-4.07), but with increased risk of major bleeding (SHR: 2.28; 95% CI, 1.09-4.79) compared with AF patients without anticoagulation (N = 139, 58.4%). Use of VKAs was associated with net clinical harm (adjusted SHR: 2.07; 95% CI, 1.25-3.42). CONCLUSIONS: Although the nonrandomized nature of the study is prone to bias, anticoagulation with VKAs was not associated with decreased thromboembolic risk, but rather with increased risk of major bleeding and may be net harmful to patients with AF on HD.
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Fibrilación Atrial , Accidente Cerebrovascular , Anticoagulantes/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Hemorragia/inducido químicamente , Humanos , Estudios Prospectivos , Diálisis Renal/efectos adversos , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiologíaRESUMEN
BACKGROUND: Information on demographics and survival of patients starting renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to multiple myeloma (MM) or light-chain deposit disease (LCDD) is scarce. The aim of this study was to describe the incidence, characteristics, causes of death and survival rates of RRT for ESRD due to MM or LCDD in the ERA-EDTA Registry. METHODS: Thirteen national registries providing data on patients who started RRT from 1986-2005 to the ERA-EDTA Registry participated. Incidence per million population (pmp) of RRT for ESRD due to MM or LCDD and other causes (non-MM) was observed overtime. Patient survival on RRT was examined, unadjusted and adjusted for age and gender. RESULTS: Of the 159 637 patients on RRT, 2453 (1.54%) had MM or LCDD. The incidence of RRT for ESRD due to MM or LCDD, adjusted for age and gender, increased from 0.70 pmp in 1986-1990 to 2.52 pmp in 2001-2005. MM and LCDD patients compared to non-MM patients were older and a higher percentage was on haemodialysis at day 91 after the start of RRT. The most common causes of death in MM and LCDD patients were malignancy (36.1%), cardiovascular causes (17.2%) and infection (14.7%). MM and LCDD patients had a 2.77 (95% CI, 2.65-2.90) higher risk of death compared to non-MM patients. The unadjusted median survival on RRT was 0.91 years in MM and LCDD patients and 4.46 years in non-MM patients. During follow-up, 35 patients were transplanted and their mean survival was 9.6 years. CONCLUSION: The incidence of RRT for ESRD due to MM or LCDD has increased over the past 20 years in Europe. The median patient survival on RRT for MM and LCDD patients was 0.91 years, compared to 4.46 years for non-MM patients. These results suggest that dialysis, and in selected cases even transplantation, should be offered to MM and LCDD patients.
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Cadenas Ligeras de Inmunoglobulina , Fallo Renal Crónico/etiología , Fallo Renal Crónico/terapia , Mieloma Múltiple/complicaciones , Paraproteinemias/complicaciones , Terapia de Reemplazo Renal , Factores de Edad , Anciano , Causas de Muerte , Femenino , Humanos , Incidencia , Agencias Internacionales , Fallo Renal Crónico/mortalidad , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Paraproteinemias/mortalidad , Sistema de Registros , Factores de Riesgo , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
We report of a 46-year-old female patient with cryptogen organizing pneumonia preceding the rare SRP positive necrotising myositis without cardiac involvement and no sign of dysphagia. Myositis showed full regression without oral immune suppression but with extracorporeal treatment, performed as a combined therapy of plasmaexchange and immunoadsorption. After 33-month of treatment, anti-SRP antibodies were not detectable any more.
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Neumonía en Organización Criptogénica/patología , Miositis/patología , Partícula de Reconocimiento de Señal/inmunología , Anticuerpos Antinucleares/sangre , Terapia Combinada , Neumonía en Organización Criptogénica/complicaciones , Neumonía en Organización Criptogénica/terapia , Femenino , Glucocorticoides/uso terapéutico , Humanos , Técnicas de Inmunoadsorción , Persona de Mediana Edad , Miositis/complicaciones , Miositis/terapia , Intercambio Plasmático , Radiografía Torácica , Pruebas de Función Respiratoria , Insuficiencia Respiratoria/complicaciones , Insuficiencia Respiratoria/patología , Insuficiencia Respiratoria/terapia , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND AND AIMS: Cardiovascular disease (CVD) is common in patients with end-stage renal disease (ESRD) on hemodialysis (HD). However, antithrombotic therapy to prevent CVD increases the risk of bleeding. We aimed to investigate the prevalence of CVD and the practice patterns of antithrombotic agents in patients with ESRD on HD. METHODS: In a cross-sectional population based cohort of chronic HD patients (n = 626) from Vienna, Austria, the medical histories of patients and use of antithrombotic treatment were recorded, and the distribution of antithrombotic therapies for primary (n = 260, 41.5%) or secondary (n = 366, 58.5%) prevention of CVD was analyzed. RESULTS: Single antiplatelet therapy (SAPT) was used in 234 patients (37.4%), dual antiplatelet (DAPT) in 50 (8.0%), combination of anticoagulation and antiplatelet in 59 (9.4%), anticoagulation monotherapy in 78 (12.5%), and no antithrombotics in 205 patients (32.7%). The prevalence of CVD was 58.5%. In primary CVD prevention, 23.5% (n = 61) of patients were treated with SAPT. For secondary prevention, SAPT was used in 173 (47.3%), DAPT in 49 (13.4%), and dual antithrombotic therapies in 50 patients (13.7%), while 55 (15.0%) patients received no antithrombotics. Age (odds ratio [OR] per 1 year increase 0.96, 95%CI 0.94-0.99, p = 0.004) and hereditary nephropathy (OR 4.13, 95%CI 1.08-15.78, p = 0.038) were independently associated with the absence of antithrombotic therapy in secondary CVD prevention. CONCLUSION: The majority of patients did not receive antithrombotic therapy for primary prevention. Only 15% did not receive antithrombotic agents in the secondary prevention setting. The net-clinical benefit of antithrombotic therapy in ESRD needs to be determined.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Fibrinolíticos/uso terapéutico , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Diálisis Renal , Prevención Secundaria , Adulto , Anciano , Anticoagulantes/uso terapéutico , Austria , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
ABO-incompatible kidney transplantation is a promising strategy for enlargement of living-donor pools. In recent years, recipient desensitization by blood group antigen-specific immunoadsorption, together with rituximab and intravenous immunoglobulin, has allowed excellent graft performance after ABO-incompatible transplantation. Adopting this protocol, originally described by Tydén and coworkers, we performed four living-donor renal transplants across the ABO barrier (A1-->0, A1-->B, B-->A1, A2-->0) between July 2007 and August 2008. Recipients were aged 25-66 years, donors 49-69 years. A protocol of on-demand immunoadsorption was followed, based on serial post-transplant antibody monitoring. Substantial and sustained decrease of blood group antibody levels was achieved in all four recipients, therefore post-transplant immunoadsorption was not needed. Graft and patient survival after 4-18 months' follow-up was 100%. Current serum creatinine was 1.3-2.0 mg/dl. Two grafts showed C4d deposits in peritubular capillaries in the complete absence of typical morphological features of antibody-mediated rejection. One recipient experienced early graft dysfunction, diagnosed as Banff borderline lesion, which responded well to steroid pulse therapy. The same recipient developed de novo interstitial fibrosis/tubular atrophy and arteriolar hyalinosis, presumably the result of suboptimal control of blood pressure and/or calcineurin inhibitor therapy. Two of the four recipients developed lymphoceles necessitating surgical revision. Apart from urinary tract infection in three patients and subclinical CMV in one, no major infectious complications were reported. Notably, two stable recipients developed polyoma BK viremia without clinical or morphological manifestations of polyomavirus-associated nephropathy. The results obtained in our small series support the earlier reported high efficiency of desensitization based on antigen-specific immunoadsorption. Nevertheless, the lack of long-term data will necessitate continuous and prudent consideration of the benefits and risks of this strategy.
Asunto(s)
Sistema del Grupo Sanguíneo ABO , Incompatibilidad de Grupos Sanguíneos/sangre , Tipificación y Pruebas Cruzadas Sanguíneas , Rechazo de Injerto/sangre , Trasplante de Riñón/métodos , Donadores Vivos , Adulto , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Austria , Biopsia , Incompatibilidad de Grupos Sanguíneos/patología , Complemento C4b/análisis , Desensibilización Inmunológica , Estudios de Seguimiento , Rechazo de Injerto/patología , Rechazo de Injerto/prevención & control , Humanos , Inmunización Pasiva , Factores Inmunológicos/uso terapéutico , Técnicas de Inmunoadsorción , Isoanticuerpos/sangre , Riñón/patología , Riñón/fisiopatología , Trasplante de Riñón/patología , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/análisis , Cuidados Preoperatorios , Rituximab , Resultado del TratamientoRESUMEN
Angiotensin-converting enzyme inhibitors (ACEis) are beneficial in patients with chronic kidney disease (CKD). Yet, their clinical effects after kidney transplantation (KTx) remain ambiguous and local renin-angiotensin system (RAS) regulation including the 'classical' and 'alternative' RAS has not been studied so far. Here, we investigated both systemic and kidney allograft-specific intrarenal RAS using tandem mass-spectrometry in KTx recipients with or without established ACEi therapy (n = 48). Transplant patients were grouped into early (<2 years), intermediate (2-12 years) or late periods after KTx (>12 years). Patients on ACEi displayed lower angiotensin (Ang) II plasma levels (P < 0.01) and higher levels of Ang I (P < 0.05) and Ang-(1-7) (P < 0.05) compared to those without ACEi independent of graft vintage. Substantial intrarenal Ang II synthesis was observed regardless of ACEi therapy. Further, we detected maximal allograft Ang II synthesis in the late transplant vintage group (P < 0.005) likely as a consequence of increased allograft chymase activity (P < 0.005). Finally, we could identify neprilysin (NEP) as the central enzyme of 'alternative RAS' metabolism in kidney allografts. In summary, a progressive increase of chymase-dependent Ang II synthesis reveals a transplant-specific distortion of RAS regulation after KTx with considerable pathogenic and therapeutic implications.
Asunto(s)
Trasplante de Riñón , Riñón/metabolismo , Riñón/fisiopatología , Sistema Renina-Angiotensina , Adulto , Angiotensina I/sangre , Angiotensina I/metabolismo , Angiotensina II/sangre , Angiotensina II/metabolismo , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Biomarcadores , Activación Enzimática/efectos de los fármacos , Femenino , Regulación Enzimológica de la Expresión Génica , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Fragmentos de Péptidos/sangre , Fragmentos de Péptidos/metabolismo , Complicaciones Posoperatorias , Renina/sangre , Renina/metabolismo , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/genéticaRESUMEN
BACKGROUND: Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) are at risk for occurrence of vascular access thrombosis and venous thromboembolism (VTE). Understanding the extent of these complications and identifying risk factors can help improve management strategies. METHODS: Adult HD patients were cross-sectionally recruited into the Vienna InVestigation of AtriaL fibrillation and thromboembolism in patients on hemoDIalysis (VIVALDI). In this investigation, retrospective data on the incidence and risk of VTE and vascular access thrombosis was analyzed using logistic regression and negative binomial regression for counts of vascular access thrombosis episodes. RESULTS: The analysis includes 626 patients on HD, which constitutes 73% of the total HD population in Vienna, Austria. One-hundred-seventy-eight patients (28.4%) had 275 vascular access thrombosis events during 2463.1 patient-years on HD, corresponding to an incidence rate (IR) of 111.6 events per 1000 patient-years on HD. In the multivariable negative binomial regression model, we found that patients suffered from vascular access thrombosis 2.5 times more often (IR ratio 2.63, 95% confidence interval [CI] 1.48-4.68, p=0.001) if toxic nephropathy was their cause of ESRD (n=28, 4.5%) compared to patients with other causes of ESRD. Sixty-one patients (9.7%) had a history of VTE and the IR of VTE events during the time on HD was 10.9 per 1000 patient-years on HD (women: IR 15.1, men IR 8.6). Female sex (odds ratio [OR] 1.90, 95%CI 1.07-3.36, p=0.029) and atrial fibrillation (OR 2.00, 95%CI 1.10-3.64, p=0.023) were independently associated with VTE. CONCLUSIONS: Thromboembolic events including vascular access thrombosis and VTE are frequent complications in patients on HD. Risk evaluation for thromboembolism, including sex and clinical parameters, may identify high-risk patients and improve their clinical management.