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1.
Kidney Int ; 105(5): 1100-1112, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38431217

RESUMEN

Thrombotic microangiopathies (TMA) are usually associated with hematological features (RH-TMA). The epidemiology of TMA limited to kidneys (RL-TMA) is unclear Therefore, patients with TMA and native kidney biopsies were identified during 2009-2022 in 20 French hospitals and results evaluated. RL-TMA was present in 341/757 (45%) patients and associated with lower creatinine levels (median 184 vs 346 µmol/L) than RH-TMA. RL-TMA resulted from virtually all identified causes, more frequently from anti-VEGF treatment and hematological malignancies but less frequently from shigatoxin-associated hemolytic uremic syndrome (HUS), systemic sclerosis, gemcitabine and bacterial infection, and even less frequently when three or more causes/triggers were combined (RL-TMA: 5%; RH-TMA: 12%). RL-TMA was associated with significantly lower major cardiovascular events (10% vs 20%), kidney replacement therapy (23% vs 43%) and death (12% vs 20%) than RH-TMA during follow-up (median 28 months). Atypical HUS (aHUS) was found in 326 patients (RL-TMA: 43%, RH-TMA: 44%). Among the 69 patients with proven complement-mediated aHUS, eculizumab (anti-C5 therapy) was used in 43 (62%) (RL-TMA: 35%; RH-TMA: 71%). Among the 257 other patients with aHUS, including 51% with RL-TMA, eculizumab was used in 29 but with unclear effects of this treatment. Thus, RL-TMA represents a very high proportion of patients with TMA and results from virtually all known causes of TMA and includes 25% of patients with complement-mediated aHUS. Adverse outcomes of RL-TMA are lower compared to RH-TMA but remain significant. Anti-C5 therapy was rarely used in RL-TMA, even in proven complement-mediated aHUS, and its effects remain to be assessed.


Asunto(s)
Síndrome Hemolítico Urémico Atípico , Microangiopatías Trombóticas , Adulto , Humanos , Riñón/patología , Microangiopatías Trombóticas/epidemiología , Microangiopatías Trombóticas/terapia , Microangiopatías Trombóticas/patología , Síndrome Hemolítico Urémico Atípico/tratamiento farmacológico , Síndrome Hemolítico Urémico Atípico/epidemiología , Proteínas del Sistema Complemento , Pruebas de Función Renal
2.
Clin J Am Soc Nephrol ; 18(11): 1435-1445, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37615951

RESUMEN

BACKGROUND: C3 glomerulopathy and idiopathic immunoglobulin-mediated membranoproliferative GN (Ig-MPGN) are rare complement-mediated kidney diseases. Inherited forms of C3 glomerulopathy/Ig-MPGN are rarely described. METHODS: Three hundred ninety-eight patients with C3 glomerulopathy ( n =296) or Ig-MPGN ( n =102) from a national registry were screened for three complement genes: factor H ( CFH ), factor I ( CFI ), and C3 . Patients with rare variant (minor allele frequency <0.1%) were included. Epidemiologic, clinical, and immunologic data at diagnosis and kidney outcomes of patients were retrospectively collected. RESULTS: Fifty-three different rare variants, including 30 (57%), 13 (24%), and ten (19%) in CFH , CFI , and C3 variants, were identified in 66/398 (17%) patients. Thirty-eight (72%) variants were classified as pathogenic, including 20/30 (66%) and 11/13 (84%) variants in CFH and CFI , respectively, impairing synthesis of factor H or factor I regulators. Fifteen of 53 (27%) variants were of unknown significance. At diagnosis, 69% of patients were adult (median age of 31 years). With the exception of biologic stigma of thrombotic microangiopathy, which was more frequent in patients with CFI variants (5/14 [36%] versus 1/37 [3%] and 0% in the CFH group and C3 group, respectively, P < 0.001), the clinical and histologic features were similar among the three variants groups. The kidney outcome was poor regardless of the age at onset and treatment received. Sixty-five percent (43/66) of patients with rare variant reach kidney failure after a median delay of 41 (19-104) months, compared with 28% (55/195) after a median delay of 34 (12-143) months in the nonvariant group. Among 36 patients who received a kidney transplant, 2-year recurrence was frequent, occurring in 39% (12/31), without difference between variant groups, and led to graft failure in three cases. CONCLUSIONS: In our cohort, 17% of C3 glomerulopathy/Ig-MPGN cases were associated with rare variants in the CFH , CFI , or C3 genes. In most cases, a quantitative deficiency in factor H or factor I was identified. The presence of a rare variant was associated with poor kidney survival. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_11_08_CJN0000000000000252.mp3.


Asunto(s)
Glomerulonefritis Membranoproliferativa , Enfermedades Renales , Adulto , Humanos , Glomerulonefritis Membranoproliferativa/genética , Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Complemento C3/genética , Estudios Retrospectivos , Factor H de Complemento/genética , Inmunoglobulinas , Enfermedades Renales/genética , Fibrinógeno
3.
J Neurol ; 270(10): 5023-5033, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37392208

RESUMEN

BACKGROUND: The immune form of thrombotic thrombocytopenic purpura (iTTP) and the hemolytic and uremic syndrome (HUS) are two major forms of thrombotic microangiopathy (TMA). Their treatment has been recently greatly improved. In this new era, both the prevalence and predictors of cerebral lesions occurring during the acute phase of these severe conditions remain poorly known. AIM: The prevalence and predictors of cerebral lesions appearing during the acute phase of iTTP and Shiga toxin-producing Escherichia coli-HUS or atypical HUS were evaluated in a prospective multicenter study. METHODS: Univariate analysis was performed to report the main differences between patients with iTTP and those with HUS or between patients with acute cerebral lesions and the others. Multivariable logistic regression analysis was used to identify the potential predictors of these lesions. RESULTS: Among 73 TMA cases (mean age 46.9 ± 16 years (range 21-87 years) with iTTP (n = 57) or HUS (n = 16), one-third presented with acute ischemic cerebral lesions on magnetic resonance imagery (MRI); two individuals also had hemorrhagic lesions. One in ten patients had acute ischemic lesions without any neurological symptom. The neurological manifestations did not differ between iTTP and HUS. In multivariable analysis, three factors predicted the occurrence of acute ischemic lesions on cerebral MRI: (1) the presence of old infarcts on cerebral MRI, (2) the level of blood pulse pressure, (3) the diagnosis of iTTP. CONCLUSION: At the acute phase of iTTP or HUS, both symptomatic and covert ischemic lesions are detected in one third of cases on MRI. Diagnosis of iTTP and the presence of old infarcts on MRI are associated with the occurrence of such acute lesions as well as increased blood pulse pressure, that may represent a potential target to further improve the therapeutic management of these conditions.


Asunto(s)
Enfermedades del Sistema Nervioso Autónomo , Síndrome Hemolítico-Urémico , Púrpura Trombocitopénica Trombótica , Trombosis , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Púrpura Trombocitopénica Trombótica/complicaciones , Púrpura Trombocitopénica Trombótica/epidemiología , Púrpura Trombocitopénica Trombótica/diagnóstico , Estudios Prospectivos , Síndrome Hemolítico-Urémico/complicaciones , Síndrome Hemolítico-Urémico/epidemiología , Síndrome Hemolítico-Urémico/diagnóstico , Infarto
5.
Nephrol Dial Transplant ; 38(4): 913-921, 2023 03 31.
Artículo en Inglés | MEDLINE | ID: mdl-35791491

RESUMEN

BACKGROUND: Cancer-associated thrombotic microangiopathy (TMA) is a rare disease, with a poor prognosis. The classical treatment is urgent chemotherapy. Few data are available on the efficacy of plasma exchange (PE) and eculizumab in these patients. METHODS: Cases of cancer-related TMA treated between January 2008 and December 2019 in 12 French treatment centres were retrospectively analysed, excluding cases associated with chemotherapy and stem cell transplantation. Patients were divided into four groups depending on the treatment received: none, PE therapy alone, chemotherapy, with or without PE therapy, or eculizumab, with or without chemotherapy and PE therapy. RESULTS: The data of 59 patients with cancer-associated TMA were analysed. Twenty of these cases were related to a cancer recurrence. The cancer was metastatic in 90% of cases (53/59). Bone marrow invasion was observed in 20/41 biopsies. Some laboratory results, including disseminated intravascular coagulation high ferritin and C-reactive protein, were suggestive of cancer. None of the 16 patients whose alternative complement pathway was assessed had abnormal levels of protein expression or activity. The median survival time was 27 days. Chemotherapy was significantly associated with improved survival, with a 30-day survival rate of 85% (17/20) among patients who received PE and chemotherapy, versus 20% (3/15) among patients who received PE alone. Patients treated with eculizumab in addition to chemotherapy and PE therapy did not have longer overall survival or higher haematological remission rates than those treated with chemotherapy and PE therapy alone. Renal remission rates were non-significantly higher, and times to remission non-significantly shorter, in the eculizumab group. CONCLUSIONS: Nephrologists and oncologists should make themselves aware of cancer diagnoses in patients with TMA and bone marrow biopsies should be performed systematically in these cases. All 59 patients had poor survival outcomes, but patients treated with urgent initiation of chemotherapy survived significantly longer than those who were not.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Neoplasias , Microangiopatías Trombóticas , Humanos , Estudios Retrospectivos , Microangiopatías Trombóticas/diagnóstico , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/terapia , Riñón , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Neoplasias/complicaciones , Neoplasias/terapia
8.
Kidney Int ; 102(4): 904-916, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35752323

RESUMEN

C3 glomerulopathy (C3G) is a rare complement-mediated disease. Specific treatments are not yet available and factors predictive of kidney survival such as age, kidney function and proteinuria are not specific to C3G. The prognostic value of biomarkers of complement activation, which are pathognomonic of the diseases, remains unknown. In a large cohort of 165 patients from the French National registry, we retrospectively assess the prognostic value of C3, soluble C5b-9 (sC5b-9), C3 nephritic factor, and rare disease-predicting variants in complement genes in predicting clinical outcome of patients. By multivariate analysis age (adult onset), reduced kidney function (defined by estimated glomerular filtration rate under 60ml/min) and presence of rare disease-predicting variants in complement genes predicted risk of progression to kidney failure. Moreover, by multivariate analysis, normal C3/high sC5b-9 levels or low C3/normal sC5b-9 levels remained independently associated with a worse kidney prognosis, with the relative risk 3.7- and 8-times higher, respectively. Subgroup analysis indicated that the complement biomarker profiles independently correlated to kidney prognosis in patients with adult but not pediatric onset. In this subgroup, we showed that profiles of biomarkers C3 and/or sC5b-9 correlated with intra glomerular inflammation and may explain kidney outcomes. In children, only the presence of rare disease-predicting variants correlated with kidney survival. Thus, in an adult population, we propose a three-point C3G prognostic score based on biomarker profiles at risk, estimated glomerular filtration rate at presentation and genetic findings, which may help stratify adult patients into subgroups that require close monitoring and more aggressive therapy.


Asunto(s)
Glomerulonefritis Membranoproliferativa , Enfermedades Renales , Adulto , Biomarcadores , Niño , Complemento C3/genética , Factor Nefrítico del Complemento 3/genética , Complejo de Ataque a Membrana del Sistema Complemento , Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Glomerulonefritis Membranoproliferativa/genética , Humanos , Enfermedades Renales/diagnóstico , Enfermedades Renales/genética , Glomérulos Renales , Enfermedades Raras , Estudios Retrospectivos
9.
Res Pract Thromb Haemost ; 6(4): e12702, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35599703

RESUMEN

Background: The prevalence, prognostic role, and diagnostic value of blood pressure in immune-mediated thrombotic thrombocytopenic purpura (iTTP) and other thrombotic microangiopathies (TMAs) remain unclear. Methods: Using a national cohort of iTTP (n = 368), Shigatoxin-induced hemolytic uremic syndrome (n = 86), atypical hemolytic uremic syndrome (n = 84), and hypertension-related thrombotic microangiopathy (n = 25), we sought to compare the cohort's blood pressure profile to assess its impact on prognosis and diagnostic performances. Results: Patients with iTTP had lower blood pressure than patients with other TMAs, systolic (130 [interquartile range (IQR) 118-143] vs 161 [IQR 142-180] mmHg) and diastolic (76 [IQR 69-83] vs 92 [IQR 79-105] mmHg, both p < 0.001). The best threshold for iTTP diagnosis corresponded to a systolic blood pressure <150 mmHg. iTTP patients presenting with hypertension had a significantly poorer survival (hazard ratio 1.80, 95% confidence interval 1.07-3.04), and this effect remained significant after multivariable adjustment (hazard ratio = 1.14, 95% confidence interval 1.00-1.30). Addition of a blood pressure criterion modestly improved the French clinical score to predict a severe A disintegrin and metalloprotease with thrombospondin type 1 deficiency in patients with an intermediate score (i.e., either platelet count <30 × 109/L or serum creatinine <200 µM). Conclusions: Elevated blood pressure at admission affects the prognosis of iTTP patients and may help discriminate them from other TMA patients. Particular attention should be paid to blood pressure and its management in these patients.

10.
EClinicalMedicine ; 45: 101340, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35295665

RESUMEN

Background: Amoxicillin crystalluria (AC), potentially responsible for acute kidney injury (AKI), is reported more and more frequently in patients treated with high doses of intravenous amoxicillin (HDIVA). The main objective of this study was to evaluate AC incidence in these patients. The secondary objectives were to identify factors associated with AC and to evaluate its impact on the risk of AKI. Methods: This multicentre, observational, cohort study was conducted between Mar 18, 2014 and Aug 16, 2019 in Dijon, Nancy, and Reims University Hospitals as well as Châlon-sur-Saône, Charleville-Mézières, and Troyes general hospitals in France. Adult patients (≥18 years) treated with HDIVA and having been tested for AC at least once during treatment were included. Clinical, biological, and therapeutic characteristics of the patients were collected. A univariable mixed logistic regression model assessed the factors associated with AC. A multivariable Cox model with AC as a time-dependent variable assessed the prognostic factors for AKI. ClinicalTrials.gov number: NCT02853292. Findings: Of the 112 included patients, 27 (24.1%, 95% CI [16.2-32.0]) developed at least one episode of AC within a mean of 5.1 days. The factors associated with its occurrence were the concomitant use of angiotensin converting enzyme (ACE) inhibitors (OR=4.6, 95% CI [2.2-9.3], p<0.0001) and the decrease of urinary pH (OR=2.1 for one pH point decrease, 95% CI [1.2-3.7], p=0.009). 20 patients (17.9%) presented with AKI, within a mean time of 10.9 days. The main factor associated with the occurrence of AKI was the occurrence of AC (aHR=7.4, 95% CI [2.5-22.2], p=0.0003). Interpretation: AC occurred in a quarter of patients treated with HDIVA and was highly prognostic of AKI. Funding: None.

12.
J Nephrol ; 35(4): 1123-1134, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34224090

RESUMEN

BACKGROUND: Long-term psychosocial outcomes and health-related quality of life (HRQOL) in adults with pediatric onset of frequently relapsing or steroid-dependent idiopathic nephrotic syndrome (FRNS or SDNS) remain to be determined. METHODS: In this prospective cohort study, 59 adults with pediatric onset of FRNS/SDNS and persistent active glomerular disease in adulthood completed the GEDEPAC-2 questionnaire exploring 11 well-being domains. Data were compared to the French general population (FGP) with standardized incidence ratio ([SIR]; adjusted for period, age, gender). Regression models were performed to identify predictive factors of psychosocial well-being. RESULTS: In 82% of cases, the questionnaire was completed while the participants (n = 59; 47 men; median age = 32 years; median number of relapses = 13) were in complete remission (under specific therapy in 76% of cases). Participants had higher educational degree than in the FGP (SIR = 6.3; p < 0.01) and more frequently a managerial occupation (SIR = 3.1; p < 0.01). Social integration was acceptable with regard to marital status and experience of sexual intercourse, but experiences of discrimination were far more frequent (SIR = 12.5; p < 0.01). The SF-12 mental component summary (MCS) score was altered (Z-score = - 0.6; p < 0.01) and mean multidimensional fatigue inventory (MFI-20) global fatigue score appeared high (12). Transfer from pediatric to adult healthcare was followed by a period of discontinued care for 33% of participants. Multivariate analysis revealed a close relationship between MFI-20, physical health, and MCS. CONCLUSIONS: This study shows that pediatric onset FRNS and SDNS may have a long-term negative impact on mental HRQOL and highlights the impact of fatigue, which is often not adequately considered in routine care.


Asunto(s)
Síndrome Nefrótico , Adulto , Niño , Fatiga , Femenino , Humanos , Inmunosupresores , Masculino , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/epidemiología , Estudios Prospectivos , Calidad de Vida , Recurrencia , Esteroides
13.
Emerg Infect Dis ; 27(7): 1876-1885, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34152955

RESUMEN

We conducted a retrospective study on hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli (STEC) in 96 adults enrolled in the cohort of the National Reference Center for Thrombotic Microangiopathies network in France during 2009-2017. Most infections were caused by STEC strains not belonging to the O157 or O104 serogroups. Thirty (31.3%) patients had multiple risk factors for thrombotic microangiopathy. In total, 61 (63.5%) patients required dialysis, 50 (52.1%) had a serious neurologic complication, 34 (35.4%) required mechanical ventilation, and 19 (19.8%) died during hospitalization. We used multivariate analysis to determine that the greatest risk factors for death were underlying immunodeficiency (hazard ratio 3.54) and severe neurologic events (hazard ratio 3.40). According to multivariate analysis and propensity score-matching, eculizumab treatment was not associated with survival. We found that underlying conditions, especially immunodeficiency, are strongly associated with decreased survival in adults who have hemolytic uremic syndrome caused by STEC.


Asunto(s)
Infecciones por Escherichia coli , Síndrome Hemolítico-Urémico , Escherichia coli Shiga-Toxigénica , Adulto , Francia , Humanos , Estudios Retrospectivos , Toxina Shiga
14.
Eur J Intern Med ; 93: 78-86, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34175183

RESUMEN

CONTEXT: The management of systemic auto-immune diseases (SAID) -associated thrombotic microangiopathies (TMA) [SAID-TMA] remains debated. OBJECTIVES: To provide a demographic, clinical and therapeutic picture of SAID-TMA. METHODS: A cross-sectional analysis was conducted on adult patients presenting with SAID and TMA from the French National TMA Registry over a 20-year period. Clinical features were extracted and compared to those from a historical cohort of atypical haemolytic and uremic syndrome (aHUS) patients. RESULTS: Forty-one patients with SAID-TMA were compared to 78 patients with aHUS from a historical cohort. Connective tissue diseases (CTD) were systemic lupus erythematosus (n=18), primary Sjögren's syndrome (n=7), systemic sclerosis (n=11), mixed CTD (n=2) and 2 cases of vasculitides, including 7 overlapping forms and 8 cases of primary antiphospholipid syndromes (APLS). Patients with SAID-TMA generally had pre-existing chronic kidney failure (OR= 3.17, 95%CI: 1.204 to 7.923; p= 0.016) compared to aHUS patients, though creatinine levels were significantly lower (216 [IQR, 108-334] µmol/L vs. 368 [IQR, 170-722] µmol/L; p= 0.002). Patients were less likely to recover if renal replacement therapy was needed at onset (OR= 0.07; 0.02 to 0.34; p <0.0005). Two patients died. Thirty patients responded to immunosuppressive treatment and complete remission was achieved in 25 cases. By contrast, therapeutic plasma exchange (TPE) did not have an early effect on TMA features at Day-7 nor Day-15 (p >0.05). CONCLUSION: The management of SAID-TMA implies an early initiation of immunosuppressive drugs for flares of the associated SAID, whereas TPE seem ineffective. KEY MESSAGES.


Asunto(s)
Síndrome Antifosfolípido , Lupus Eritematoso Sistémico , Microangiopatías Trombóticas , Adulto , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/epidemiología , Estudios Transversales , Humanos , Sistema de Registros , Microangiopatías Trombóticas/epidemiología
15.
Nephrol Ther ; 17(2): 80-91, 2021 Apr.
Artículo en Francés | MEDLINE | ID: mdl-33551369

RESUMEN

Contrast media administration is classically considered to cause or worsen kidney failure. Recent data may moderate this assertion. The European Society of Urogenital Radiology recently published guidelines re-evaluating the precautions before administering contrast media. The present work evaluates the practice of French nephrologists, and provides a commentary on these recommendations based on an updated review of the literature. We conducted survey among French nephrologists, using an electronic questionnaire distributed by the Société Francophone de Néphrologie, Dialyse et Transplantation, the French Intensive care Renal Network and the Club des Jeunes Néphrologues. 266 responses were collected. The European Society of Urogenital Radiology guidelines are poorly known among the panel of nephrologists. Their practices differ from the guidelines by the more frequent and earlier implementation of measures to prevent renal failure post contrast media. In accordance with the guidelines, hydration is prescribed as a first-line preventive measure, mainly with saline and bicarbonate. Inhibitors of the renin-angiotensin-aldosterone system are frequently discontinued before an injection of contrast media, contrary to what is recommended. In conclusion, the European Society of Urogenital Radiology guidelines, which the working group endorses, but which are still too little known and applied in clinical nephrology in France, prompt nephrologists to lift some of the restrictions on the use of PCI as well as on the continuation of ARS inhibitors before injecting PCI.


Asunto(s)
Nefrología , Intervención Coronaria Percutánea , Medios de Contraste/efectos adversos , Humanos , Nefrólogos , Encuestas y Cuestionarios
16.
Diagn Interv Imaging ; 102(3): 131-139, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33531265

RESUMEN

Contrast medium administration is classically considered to cause or worsen kidney failure, but recent data may moderate this assertion. The European Society of Urogenital Radiology recently published guidelines re-evaluating the precautions before administering contrast media. Kidney injury does not constitute a contra-indication to the administration of iodinated contrast medium, as long as the benefit-risk ratio justifies it. Intravenous hydration with 0.9% NaCl or 1.4% sodium bicarbonate is the only validated measure for the prevention of post-iodine contrast nephropathy. This is necessary for intravenous or intra-arterial administration of iodinated contrast agent without first renal pass when the glomerular filtration rate is less than 30mL/min/1.73m2, for intra-arterial administration of iodinated contrast agent with first renal passage when the glomerular filtration rate is less than 45mL/min/1.73m2, or in patients with acute renal failure. The use of iodinated contrast medium should allow the carrying out of relevant examinations based on an analysis of the benefit-risk ratio and the implementation of measures to prevent toxicity when necessary.


Asunto(s)
Lesión Renal Aguda , Medios de Contraste , Riñón , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/prevención & control , Medios de Contraste/administración & dosificación , Medios de Contraste/efectos adversos , Adhesión a Directriz , Humanos , Riñón/diagnóstico por imagen , Riñón/efectos de los fármacos , Nefrología , Guías de Práctica Clínica como Asunto , Radiografía , Radiología , Factores de Riesgo , Bicarbonato de Sodio/administración & dosificación
17.
Blood ; 137(6): 733-742, 2021 02 11.
Artículo en Inglés | MEDLINE | ID: mdl-33150928

RESUMEN

The anti-von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.


Asunto(s)
Corticoesteroides/uso terapéutico , Intercambio Plasmático , Púrpura Trombocitopénica Trombótica/terapia , Rituximab/uso terapéutico , Anticuerpos de Dominio Único/uso terapéutico , Proteína ADAMTS13/sangre , Adulto , Terapia Combinada , Ensayos de Uso Compasivo , Progresión de la Enfermedad , Quimioterapia Combinada , Femenino , Hemorragia/inducido químicamente , Estudio Históricamente Controlado , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Estudios Prospectivos , Púrpura Trombocitopénica Trombótica/sangre , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Púrpura Trombocitopénica Trombótica/mortalidad , Índice de Severidad de la Enfermedad , Anticuerpos de Dominio Único/efectos adversos , Anticuerpos de Dominio Único/economía , Tromboembolia/etiología , Resultado del Tratamiento , Factor de von Willebrand/antagonistas & inhibidores
18.
Clin Kidney J ; 13(5): 878-888, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33354330

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, related to severe acute respiratory syndrome coronavirus 2 infection. Few data are available in patients with end-stage renal disease (ESRD). METHODS: We conducted an observational cohort study of COVID-19 patients at 11 dialysis centres in two distinct districts of France to examine the epidemiological and clinical characteristics of COVID-19 in this population, and to determine risk factors of disease severity (defined as a composite outcome including intensive care unit admission or death) and mortality. RESULTS: Among the 2336 patients enrolled, 5.5% had confirmed COVID-19 diagnosis. Of the 122 patients with a follow-up superior to 28 days, 37% reached the composite outcome and 28% died. Multivariate analysis showed that oxygen therapy on diagnosis and a decrease in lymphocyte count were independent risk factors associated with disease severity and with mortality. Chronic use of angiotensin II receptor blockers (ARBs) (18% of patients) was associated with a protective effect on mortality. Treatment with azithromycin and hydroxychloroquine (AZT/HCQ) (46% of patients) were not associated with the composite outcome and with death in univariate and multivariate analyses. CONCLUSIONS: COVID-19 is a severe disease with poor prognosis in patients with ESRD. Usual treatment with ARBs seems to be protective of critical evolution and mortality. There is no evidence of clinical benefit with the combination of AZT/HCQ.

19.
Clin Case Rep ; 8(12): 2641-2644, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33363796

RESUMEN

Eculizumab may be considered as an emergency therapeutic option in refractory life-threatening warm autoimmune hemolytic anemia especially if direct antiglobulin test is positive for both IgG and C3d and after failure of all conventional treatments.

20.
Nephrol Dial Transplant ; 35(9): 1619-1628, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32678426

RESUMEN

BACKGROUND: Moderate hyperhydration is often achieved in the early post-kidney transplantation period. Whether this strategy could lead to the development of intra-abdominal hypertension (IAH) has never been assessed so far. We aimed to study the incidence of IAH after kidney transplantation and its association with graft function recovery. METHODS: We conducted a prospective monocentric study among patients undergoing kidney transplantation at the University Hospital of Reims between May 2017 and April 2019. Intravesical pressure (IVP) was monitored every 8 h from Day 0 to 3. RESULTS: A total of 107 patients were enrolled. Among 55 patients included in the analysis, 74.5% developed IAH. Body mass index >25 kg/m2 was associated with IAH development {odds ratio [OR] 10.4 [95% confidence interval (CI) 2.0-52.9]; P = 0.005}. A previous history of peritoneal dialysis was protective [OR 0.06 (95% CI 0.01-0.3); P = 0.001]. IAH Grades III and IV occurred in 30.9% of patients and correlated with higher Day 3 creatininaemia (419.6 ± 258.5 versus 232.5 ± 189.4 µmol/L; P = 0.02), higher delayed graft function incidence (41.2 versus 7.9%; P = 0.04), lower Kirchner index measured using scintigraphy (0.47 ± 0.09 versus 0.64 ± 0.09; P = 0.0005) and decreased Day 30 estimated glomerular filtration rate (35.8 ± 18.8 versus 52.5 ± 21.3, P = 0.05). IAH patients had higher fluid balance (P = 0.02). Evolution of IVP correlated with weight gain (P < 0.01) and central venous pressure (P < 0.001). CONCLUSIONS: IAH is frequent after kidney transplantation and IAH Grades III and IV are independently associated with impaired graft function. These results question current haemodynamic objectives and raise for the first time interest in intra-abdominal pressure monitoring in these patients. CLINICAL TRIAL NOTATION: ClinicalTrials.gov identifier: NCT03478176.


Asunto(s)
Rechazo de Injerto/etiología , Hipertensión Intraabdominal/epidemiología , Trasplante de Riñón/efectos adversos , Femenino , Francia/epidemiología , Tasa de Filtración Glomerular , Rechazo de Injerto/epidemiología , Rechazo de Injerto/patología , Hemodinámica , Humanos , Incidencia , Hipertensión Intraabdominal/etiología , Hipertensión Intraabdominal/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Equilibrio Hidroelectrolítico
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