RESUMEN
OBJECTIVE: The long-term outcome of allogenic islet transplantation is unknown. The aim of this study was to evaluate the 10-year outcome of islet transplantation in patients with type 1 diabetes and hypoglycemia unawareness and/or a functioning kidney graft. RESEARCH DESIGN AND METHODS: We enrolled in this prospective parallel-arm cohort study 28 subjects with type 1 diabetes who received islet transplantation either alone (ITA) or after a kidney graft (IAK). Islet transplantation consisted of two or three intraportal infusions of allogenic islets administered within (median [interquartile range]) 68 days (43-92). Immunosuppression was induced with interleukin-2 receptor antibodies and maintained with sirolimus and tacrolimus. The primary outcome was insulin independence with A1C ≤6.5% (48 mmol/mol). Secondary outcomes were patient and graft survival, severe hypoglycemic events (SHEs), metabolic control, and renal function. RESULTS: The primary outcome was met by (Kaplan-Meier estimates [95% CI]) 39% (22-57) and 28% (13-45) of patients 5 and 10 years after islet transplantation, respectively. Graft function persisted in 82% (62-92) and 78% (57-89) of case subjects after 5 and 10 years, respectively, and was associated with improved glucose control, reduced need for exogenous insulin, and a marked decrease of SHEs. ITA and IAK had similar outcomes. Primary graft function, evaluated 1 month after the last islet infusion, was significantly associated with the duration of graft function and insulin independence. CONCLUSIONS: Islet transplantation with the Edmonton protocol can provide 10-year markedly improved metabolic control without SHEs in three-quarters of patients with type 1 diabetes, kidney transplanted or not.
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Diabetes Mellitus Tipo 1/cirugía , Trasplante de Islotes Pancreáticos/métodos , Trasplante de Riñón/métodos , Adulto , Glucemia/metabolismo , Terapia Combinada , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/epidemiología , Hipoglucemia/etiología , Hipoglucemiantes/administración & dosificación , Terapia de Inmunosupresión/métodos , Insulina/administración & dosificación , Trasplante de Islotes Pancreáticos/efectos adversos , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Further study is needed on the prognostic impact of cirrhosis on haemodialysis patients. AIM: To evaluate cirrhosis' impact according to severity on survival and to provide therapeutic guidelines for haemodialysis cirrhotic patients. METHODS: Patients with end-stage renal failure treated with haemodialysis were included retrospectively from 01/01/2000 to 31/12/2004 and prospectively from 01/01/2005 to 31/12/2014 in our French Region. Clinical data, presence of cirrhosis and its severity were recorded at the beginning of haemodialysis. The primary endpoint was 2-year survival. RESULTS: Seven thousand three hundred and fifty-four patients (96%) without cirrhosis and 304 patients (4%) with cirrhosis were included. Two-year survival in noncirrhotic patients was higher than in cirrhotic patients (71.7% vs 54.4%, P < 0.0001). Patients with decompensated cirrhosis had a worse 2-year outcome (44.1%) as compared to compensated cirrhotic (62.8%, P = 0.002) and noncirrhotic patients (71.7%, P < 0.0001). Compensated and decompensated cirrhosis were independent predictive factors of 2-year mortality. In sensitivity analysis restricted to cirrhotic patients, 2-year survival of Child-Pugh A patients was higher than in Child-Pugh B and C patients (65.5% vs 27.7% vs 0%, P < 0.0001). Development of predictive models based either on severity scores (MELD and Child-Pugh) and extrahepatic comorbidities allowed correct classification of around 70% of patients in terms of mortality and may help to better stratify mortality risk in this population. CONCLUSIONS: Cirrhosis is independently associated with mortality in haemodialysis patients. Patients with severe cirrhosis have a poor 2-year outcome. Severity of cirrhosis and presence of extrahepatic comorbidities should be considered when deciding to initiate renal replacement therapy.
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Fallo Renal Crónico/terapia , Cirrosis Hepática/terapia , Diálisis Renal , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Drug related problems (DRP) can lead to severe consequences in kidney recipients. The aim of the study was to assess the impact of the clinical pharmacist interventions on the incidence of DRP. METHOD: The number of DRP were evaluated according to 3periods: Without intervention, with medication reconciliation at admission, and with medication reconciliation at admission associated with an interview with the clinical pharmacist at discharge. RESULTS: Patients concerned were mainly men, 55years old (median age), stage3 of CKD, transplanted for less than 3months or more than 1year, with cardiovascular risk factors and receiving an average of 9drugs/day. Among the DRP, 20% were avoidable and severe in most cases. In period1, 27.7% patients had at least 1DRP, in period2, 21.3% patients had at least 1DRP, and in period3, 17.4% of patients had at least 1DRP (P=0.03). One hundred and ten patients had medication reconciliation at admission with a mean of 0.6unintentional discrepancies per patient (omission in 81% of cases). The main drugs involved concerned the digestive-metabolic (24.5%), cardiovascular (23%), and nervous (23%) system. Sixty-eight interviews at discharge were realized and revealed self-medication habits. CONCLUSION: Our study shows that medication reconciliation at admission associated with an interview with the clinical pharmacist at discharge can help to reduce DRP in kidney recipients. Further studies are needed to confirm our results.
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Trasplante de Riñón/efectos adversos , Errores de Medicación/prevención & control , Conciliación de Medicamentos/métodos , Insuficiencia Renal Crónica/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Humanos , Masculino , Errores de Medicación/estadística & datos numéricos , Persona de Mediana Edad , Alta del Paciente , Farmacéuticos/estadística & datos numéricos , Insuficiencia Renal Crónica/cirugíaRESUMEN
We report a case of a 43 years old man who was intoxicated by a 25g vancomycin overload. An anuric acute renal failure rapidly occured. The vancomycinemia was measured as high as 360mg/L (normal range: 15-35mg/L). We started an intermittent hemodialysis program to clear out the vancomycin. The vancomycinemia decreased below the treshold of our laboratory after the eighth session. Three supplementary sessions were needed because of a persistant oliguria. The kidney function slowly improved and was back to normal (seric creatinin: 80micromol/L) 3 weeks after the patient had gone home. To our knowledge, it is the first success of this technic concerning vancomycin poisoning in adults with anuric kidney failure.
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Lesión Renal Aguda/inducido químicamente , Antibacterianos/envenenamiento , Diálisis Renal/métodos , Vancomicina/envenenamiento , Lesión Renal Aguda/terapia , Adulto , Antibacterianos/sangre , Humanos , Masculino , Vancomicina/sangreRESUMEN
The study of calcineurin inhibitor (CNI) blood level variability to evaluate adherence in transplantation has improved over the years. The aim of our study was to assess factors associated with this variability using the coefficient of variation (CV). A cross-sectional sample of kidney recipients grafted for more than 1 year was recruited. We recorded clinical data, data from a clinical pharmacist interview and from six questionnaires measuring adherence, satisfaction, behaviours, beliefs, perception of the illness and social vulnerability. A total of 408 recipients were enrolled (61.2% male, mean age 54) and divided into two groups: low variability CV < 30% (n = 302), high variability CV ≥ 30% (n = 106). In univariate analysis, hospital-home distance, cyclosporine, time since transplantation and presence of discrepancies in drug regimen were associated with a greater risk of CV ≥ 30%. In contrast, tacrolimus QD conferred a lower risk of CV ≥ 30%. In multivariate analysis, only the presence of discrepancies remained significant: (OR 3.2 [1.21-9.01]; P = 0.022). Discrepancies in drug regimen appear as the main risk factor associated with CNI blood variability. The clinical pharmacist's input is an accurate and simple way of detecting non-adherence which is not revealed in self-report questionnaires.
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Inhibidores de la Calcineurina/sangre , Ciclosporina/sangre , Inmunosupresores/sangre , Trasplante de Riñón , Cumplimiento de la Medicación , Tacrolimus/sangre , Adulto , Inhibidores de la Calcineurina/administración & dosificación , Distribución de Chi-Cuadrado , Estudios Transversales , Ciclosporina/administración & dosificación , Esquema de Medicación , Monitoreo de Drogas , Femenino , Humanos , Inmunosupresores/administración & dosificación , Trasplante de Riñón/efectos adversos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Satisfacción del Paciente , Factores de Riesgo , Encuestas y Cuestionarios , Tacrolimus/administración & dosificación , Factores de Tiempo , Resultado del TratamientoRESUMEN
In renal transplant medicine, several scores have been recently developed in order to help decision-making in clinical practice. The aim of this update is to focus on these new scores that allow to better estimate the quality of the renal transplant, to refine the allocation policy, to help registration of old recipients on the waiting list, or to evaluate the risk to develop end-stage renal failure after living donation.
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Selección de Donante , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Donadores Vivos , Cadáver , Toma de Decisiones Clínicas , Selección de Donante/métodos , Francia , Humanos , Trasplante de Riñón/métodos , Donadores Vivos/provisión & distribución , Listas de EsperaRESUMEN
Pneumocystis pneumonia (PCP) incidence was decreased in renal transplant thanks to prophylaxis, recommended during the first months after transplantation. However, many late PCP cases are observed after the first 6 months and recommendations to maintain or reintroduce prophylaxis are lacking. The objective of the study was to identify risk factors to guide the individual prescription of prophylaxis, 6 months after transplantation. Thirty-three late PCP cases were identified between 1995 and 2012 in Lille Hospital, France, and were compared to 72 randomized controls transplant recipients. In univariate analysis, age of donor (>48 years), retransplantation, a decrease glomerular filtration rate (≤45 mL/min), induction therapy mediated by anti-thymocyte globulin (ATG), steroid maintenance, high calcineurin inhibitors (CNI) doses (tacrolimus ≥0.5 mg/kg/day and cyclosporine ≥2.1 mg/kg/day), and cytomegalovirus (CMV) infection were significantly associated with PCP. In multivariate analysis, ATG (hazard ratio [HR]: 2.4 [1.1-5.4]), steroid therapy (HR: 3.1 [1.20-7.84], CNI (HR: 2.9 [1.28-6.38], and CMV (HR: 6.1 [2.74-16.33] remained associated with late PCP. In conclusion, we confirm that intensive immunosuppressive regimen and CMV infection are critical risk factors for late PCP and should be taken into account to decide on maintenance or reintroduction of a prophylactic treatment.
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Trasplante de Riñón/efectos adversos , Neumonía por Pneumocystis/etiología , Adulto , Anciano , Estudios de Casos y Controles , Infecciones por Citomegalovirus , Femenino , Francia/epidemiología , Rechazo de Injerto , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Neumonía por Pneumocystis/epidemiología , Factores de RiesgoRESUMEN
RATIONALE: BRAF and MEK inhibitors have significantly improved the prognosis of metastatic melanoma, by inhibiting both the mitogen-activated protein kinase (MAP-kinase) pathway. They are associated with infrequent adverse kidney events. Most of these are related to the use of BRAF inhibitors and involve interstitial nephritis with acute tubular necrosis. PATIENT CONCERNS: We report a unique case of glomerulonephritis with renal granulomatous vasculitis in a patient diagnosed with metastatic melanoma treated with BRAF and MEK inhibitors. The patient was a 55-year old woman, who presented a melanoma of the right thigh with pulmonary metastasis. Treatment started in November 2015, with Encorafenib and Binimetinib, new BRAF and MEK inhibitors, respectively. Two months after the beginning of the treatment, there was a worsening of her renal function with significant proteinuria. DIAGNOSES: Kidney biopsy showed extracapillary proliferation in the glomeruli with a granulomatous reaction. INTERVENTIONS AND OUTCOMES: Renal function recovered completely after withdrawal of the chemotherapy. LESSONS: All the reported kidney adverse events secondary to BRAF and MEK inhibitors in the literature are related to the use of BRAF inhibitors. Some previous reported mechanistic investigations also provide insight between BRAF inhibitors and podocytes injuries. Therefore, encorafenib most likely is the main responsible of the disease. However, evidence has emerged that inhibition of the MAP kinase pathway could also enhance autoimmunity. Thus, binimetinib may also have played a role and the combination of BRAF and MEK inhibitors may have facilitated this autoimmune kidney disease.
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Antineoplásicos/efectos adversos , Glomerulonefritis/inducido químicamente , Neoplasias Pulmonares/tratamiento farmacológico , Quinasas Quinasa Quinasa PAM/antagonistas & inhibidores , Melanoma/tratamiento farmacológico , Vasculitis/inducido químicamente , Antineoplásicos/uso terapéutico , Bencimidazoles/efectos adversos , Bencimidazoles/uso terapéutico , Carbamatos/efectos adversos , Carbamatos/uso terapéutico , Femenino , Glomerulonefritis/sangre , Glomerulonefritis/patología , Humanos , Riñón/irrigación sanguínea , Riñón/efectos de los fármacos , Riñón/patología , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/secundario , Melanoma/sangre , Melanoma/patología , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Vasculitis/sangre , Vasculitis/patologíaRESUMEN
Background Medication non-adherence is a major issue after transplant that can lead to misdiagnosis, rejection, poor health affecting quality of life, graft loss or death. Several estimations of adherence and related factors have previously been described but conclusions leave doubt as to the most accurate assessment method. Aim of the review To identify the factors most relevant to medication non-adherence in kidney transplant in current clinical practice. Method This systematic review is registered in the PROSPERO data base and follows the Prisma checklist. Articles in English in three databases from January 2009 to December 2014 were analysed. A synthesis was made to target adherence assessment methods, their prevalence and significance. Results Thirty-seven studies were analysed rates of non-adherence fluctuating from 1.6 to 96%. Assessment methods varied from one study to another, although self-reports were mainly used. It appears that youth (≤50 years old), male, low social support, unemployment, low education, ≥3 months post graft, living donor, ≥6 comorbidities, ≥5 drugs/d, ≥2 intakes/d, negative beliefs, negative behavior, depression and anxiety were the factors significantly related to non-adherence. Conclusion As there are no established guidelines, consideration should be given to more than one approach to identify medication non-adherence although self-reports should remain the cornerstone of adherence assessment.
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Inmunosupresores/administración & dosificación , Trasplante de Riñón/métodos , Cumplimiento de la Medicación , Rechazo de Injerto/prevención & control , Humanos , Calidad de Vida , Factores de Riesgo , Autoinforme , Apoyo SocialRESUMEN
BACKGROUND: Home telemonitoring has developed considerably over recent years in chronic diseases in order to improve communication between healthcare professionals and patients and to promote early detection of deteriorating health status. In the nephrology setting, home telemonitoring has been evaluated in home dialysis patients but data are scarce concerning chronic kidney disease (CKD) patients before and after renal replacement therapy. The eNephro study is designed to assess the cost effectiveness, clinical/biological impact, and patient perception of a home telemonitoring for CKD patients. Our purpose is to present the rationale, design and organisational aspects of this study. METHODS: eNephro is a pragmatic randomised controlled trial, comparing home telemonitoring versus usual care in three populations of CKD patients: stage 3B/4 (n = 320); stage 5D CKD on dialysis (n = 260); stage 5 T CKD treated with transplantation (n= 260). Five hospitals and three not-for-profit providers managing self-care dialysis situated in three administrative regions in France are participating. The trial began in December 2015, with a scheduled 12-month inclusion period and 12 months follow-up. Outcomes include clinical and biological data (e.g. blood pressure, haemoglobin) collected from patient records, perceived health status (e.g. health related quality of life) collected from self-administered questionnaires, and health expenditure data retrieved from the French health insurance database (SNIIRAM) using a probabilistic matching procedure. DISCUSSION: The hypothesis is that home telemonitoring enables better control of clinical and biological parameters as well as improved perceived health status. This better control should limit emergency consultations and hospitalisations leading to decreased healthcare expenditure, compensating for the financial investment due to the telemedicine system. TRIAL REGISTRATION: This study has been registered at ClinicalTrials.gov under NCT02082093 (date of registration: February 14, 2014).
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Atención a la Salud/métodos , Medicina General , Nefrología , Insuficiencia Renal Crónica/terapia , Telemedicina/métodos , Determinación de la Presión Sanguínea , Peso Corporal , Servicios de Laboratorio Clínico , Comunicación , Análisis Costo-Beneficio , Atención a la Salud/economía , Manejo de la Enfermedad , Registros Electrónicos de Salud , Francia , Humanos , Internet , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/terapia , Trasplante de Riñón , Relaciones Médico-Paciente , Diálisis Renal , Insuficiencia Renal Crónica/economía , Insuficiencia Renal Crónica/fisiopatología , Índice de Severidad de la Enfermedad , Evaluación de Síntomas , Telemedicina/economíaRESUMEN
PURPOSE: This study examines the effect of Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) on renal function for at least 5 years post-operatively in a tertiary referral center for bariatric surgery. MATERIALS AND METHODS: This prospective cohort study of patients undergoing RYGB and LAGB measured renal function, blood pressure, and diabetes status pre-operatively and then 1 and 5 years post-operatively. Renal function was assessed using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockcroft-Gault formulae. Hypertension and diabetes were defined by the European Society of Hypertension and European Society of Cardiology joint guidelines and American Diabetes Association guidelines, respectively. A sub-group who had completed 10 years post-operative follow-up was also included. RESULTS: Estimated glomerular filtration rate (eGFR) increased over 5 years after RYGB (N = 190; 94 ± 2 mL/min/1.73 m2 to 102 ± 22 mL/min/1.73 m2, p = 0.01) and LAGB (N = 271; 88 ± 1 to 93 ± 22 mL/min/1.73 m2, p = 0.02). In a sub-group with up to 10 years post-operative date, this trend was maintained. In patients with renal impairment, eGFR improved over 5 years (52 ± 2 to 68 ± 7 mL/min/1.73 m2, p = 0.01). Remission of hypertension was greater after RYGB than LAGB at 1 year (32 vs. 16 %, p = 0.008) and at 5 years post-operatively (23 vs. 11 %, p = 0.02). CONCLUSIONS: Bariatric surgery stabilizes eGFR post-operatively for at least 5 years. In a sub-group with renal impairment, eGFR is increased in the first post-operative year and this is maintained for up to 5 years. RYGB is an effective procedure in achieving blood pressure control.
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Cirugía Bariátrica , Hipertensión/cirugía , Riñón/fisiología , Obesidad Mórbida/cirugía , Adulto , Cirugía Bariátrica/métodos , Femenino , Estudios de Seguimiento , Derivación Gástrica/métodos , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Pruebas de Función Renal/efectos adversos , Masculino , Persona de Mediana Edad , Obesidad Mórbida/complicaciones , Obesidad Mórbida/fisiopatología , Periodo Posoperatorio , Estudios Prospectivos , Inducción de Remisión , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/cirugía , Pérdida de Peso/fisiologíaRESUMEN
Chronic kidney disease (CKD) is a major concern of public health. The pharmacist is known as a health practitioner involved in prevention and therapeutic education. Our study aimed at defining the impact of community pharmacists' interventions for preventing and screening CKD. In our observational prospective study of 5 months conducted in 109 community pharmacy, we included 2 groups of patients: A (therapeutic optimization): CKD patients and B (CKD screening): population at risk. In group A, we included 354 patients, mainly women (51.2%), in stage 3 of CKD, mean age 73 years old, with hypertension alone (40.6%) or associated with diabetes (44%). About 70% of the patients had a follow up by a nephrologist and 45% of them were good adherent according to the Morisky-Green self-report. However, approximately 20% of patients did not have nephroprotective treatments in their regimen although they were on stage 3 or 4 CKD patients, and about half of them were not aware of medical situations at risk. Concerning group B, 532 patients were included. The pharmaceutical interventions screened 10% of patients with a GFR<60mL/min/1.73m2. The community pharmacists' interventions helped to optimize the therapeutic management of CKD patients and in the early screening of patients at risk. More studies are needed to extrapolate our observations to a larger population.
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Farmacéuticos , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/prevención & control , Anciano , Femenino , Francia , Tasa de Filtración Glomerular , Humanos , Masculino , Tamizaje Masivo , Estudios ProspectivosRESUMEN
BACKGROUND: Despite long-term side effects, calcineurin inhibitors (CNI) remain a cornerstone of immunosuppression in renal transplantation. Few trials assessed the long-term outcome after early CNI withdrawal. METHODS: This intention-to-treat study assessed the 10-year outcome of 108 patients randomly converted from a cyclosporine (CsA)-mycophenolate mofetil (MMF)-prednisone regimen to a dual therapy (CsA-prednisone or MMF-prednisone) at 3 months postgraft. RESULTS: At 10 years, 3.7% in the CsA group and 35.2% in the MMF group remained on the protocol regimen (P<.001). eGFR was higher in the MMF group (64.4±21 vs 49.7±14.7 mL/min/1.73 m², P<.001), although acute rejection (12 vs 4 in the CsA group, P=.03) and Class II DSA incidences were increased. CNI-related toxicity (P=.019) and moderate-to-severe IF/TA (P=.004) were higher in the CsA group. Ten-year graft and patient survivals were not different. In multivariate analysis, acute rejection remained the strongest predictor of graft loss (HR=11.64, 95% CI [5.05-26.79], P<.0001). CONCLUSIONS: MMF withdrawal largely failed due to CNI toxicity, while CsA withdrawal led to increased graft failure due to uncontrolled acute rejection without increasing graft survival. From this study, it remains unclear which patients could benefit from limiting CNI exposure.
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Inhibidores de la Calcineurina/administración & dosificación , Ciclosporina/administración & dosificación , Rechazo de Injerto/prevención & control , Inmunosupresores/administración & dosificación , Trasplante de Riñón , Inhibidores de la Calcineurina/uso terapéutico , Ciclosporina/uso terapéutico , Esquema de Medicación , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Análisis de Intención de Tratar , Trasplante de Riñón/mortalidad , Masculino , Ácido Micofenólico/uso terapéutico , Prednisona/uso terapéutico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Thrombotic microangiopathy (TMA) is a poorly recognized cause of collapsing glomerulopathy. The frequency and significance of collapsing glomerulopathy associated with renal TMA have not been specifically studied in native kidney biopsy specimens. Here we retrospectively documented clinicopathologic features of 53 patients with histologically proven TMA in the native kidney, with special emphasis on changes due to focal segmental glomerulosclerosis (FSGS). Histological TMA was related to hypertensive nephropathy in 21 patients, genetic complement abnormalities in 9, drugs in 7, and to other causes in 16 patients. Almost half (26 patients) presented with arteriolar, 6 with glomerular, and 21 with mixed TMA. Using the Columbia classification system for the 53 patients with histological TMA, 33 had concurrent FSGS lesions with collapsing glomerulopathy the dominant variant in 19 patients (58% of the FSGS cases), not otherwise specified in 9 patients, cellular in 3, and perihilar or tip lesions in 1 patient each. The presence of FSGS was associated with a poor renal prognosis, with no prognostic difference between collapsing glomerulopathy and other FSGS variants. Thus, collapsing glomerulopathy is frequently found in native kidney biopsies with TMA, suggesting that endothelial injury may play an important role in the pathophysiology of FSGS.
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Glomeruloesclerosis Focal y Segmentaria/etiología , Riñón/patología , Microangiopatías Trombóticas/complicaciones , Adulto , Anciano , Femenino , Francia/epidemiología , Glomeruloesclerosis Focal y Segmentaria/epidemiología , Glomeruloesclerosis Focal y Segmentaria/patología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Adulto JovenRESUMEN
IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis, whose prognosis is highly variable. Interstitial fibrosis is a strong independent prognosis factor. Among microRNA involved in renal fibrogenesis, only few have been investigated in IgAN. In the context of IgAN, we aimed to analyze the role of miR-21-5p, miR-214-3p and miR-199a-5p, three established "fibromiRs" involved in renal fibrosis. Fifty-six IgAN biopsy specimens were retrospectively scored according to Oxford classification. Renal expression of miR-21-5p, miR-214-3p and miR-199a-5p were significantly associated with T score (miR-21-5p T0 RQ median = 1.23, T1 RQ = 3.01, T2 RQ = 3.90; miR-214-5p T0 RQ = 1.39, T1 RQ = 2.20, T2 RQ = 2.48; miR-199a-5p T0 RQ = 0.76, T1 RQ = 1.41, T2 RQ = 1.87). miR-21-5p expression was associated with S score (S0 RQ median = 1.31, S1 RQ = 2.65), but not miR-214-3p nor miR-199a-5p. In our cohort, poor renal survival was associated with high blood pressure, proteinuria and elevated creatininemia, as well as T and S scores. Moreover, renal expression of miR-21-5p, miR-214-3p were associated with renal survival. In conclusion, miR-21-5p, miR-214-3p and miR-199a-5p are three "fibromiRs" involved in renal fibrosis in the course of IgAN and miR-21-5p and miR-214-3p are associated with renal survival.
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Glomerulonefritis por IGA/genética , Glomerulonefritis por IGA/patología , Riñón/patología , MicroARNs/genética , Adulto , Femenino , Fibrosis , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Regulación hacia Arriba , Adulto JovenRESUMEN
BACKGROUND: Pregnancy-related renal cortical necrosis may lead to end-stage renal disease. Although this obstetric complication had virtually disappeared in high-income countries, we have noted new cases in France over the past few years, all following postpartum hemorrhage. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We retrospectively identified 18 patients from 5 French nephrology departments who developed renal cortical necrosis following postpartum hemorrhage in 2009 to 2013. OUTCOMES: Obstetric and renal features, therapeutic measures, and kidney disease outcome were studied. RESULTS: All patients had a severe postpartum hemorrhage (mean blood loss, 2.6±1.1 [SD] L). Hemodynamic instability and disseminated intravascular coagulation were reported in 5 and 11 patients, respectively. All developed rapid onset of acute kidney injury and required hemodialysis. Diagnosis of renal cortical necrosis was performed 4 to 33 days following delivery. At 6 months postpartum, 8 patients remained dialysis dependent and none recovered normal kidney function. The length of exposure to tranexamic acid treatment was significantly more prolonged in women whose estimated glomerular filtration rate remained <15mL/min/1.73m(2) (7.1±4.8 vs 2.9±2.4 hours; P=0.03). LIMITATIONS: Retrospective study; small sample size. CONCLUSIONS: In the setting of gravid endothelium, the conjunction of disseminated intravascular coagulation with the life-saving use of procoagulant and antifibrinolytic agents (recently implemented in France in a postpartum hemorrhage treatment algorithm) may give rise to a risk for uncontrolled clotting in the renal cortex and hence irreversible partial or diffuse cortical necrosis.
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Necrosis de la Corteza Renal/etiología , Hemorragia Posparto , Adulto , Femenino , Francia , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: Use of a hospital pneumatic tube system may be associated with measurement errors. METHODS: A venous blood sample was collected from 79 patients into a pair of lithium heparin tubes; one tube was sent to the laboratory by porter and the other was sent via the pneumatic tube system. Plasma lactate dehydrogenase concentrations were then assayed. RESULTS: Lactate dehydrogenase concentrations were overestimated (median bias: 18.8%) when evacuated vacuum lithium heparin tubes were sent by pneumatic tube system. This bias was reduced by bubble-wrapping the standard lithium heparin tube or using Monovette lithium heparin tubes in aspiration mode (median bias: +8.7% and -0.3%, respectively). CONCLUSIONS: Cushioning and aspiration-mode sampling may limit pneumatic tube system-associated overestimation of lactate dehydrogenase concentrations.
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L-Lactato Deshidrogenasa/sangre , Flebotomía/métodos , Humanos , Flebotomía/instrumentación , Flebotomía/normas , Manejo de EspecímenesRESUMEN
After detection of small cell lung cancer in a 67-year-old patient who had donated a kidney 7 months earlier, the graft recipient underwent FDG-PET/CT to determine the presence/absence of tumor cell transmission. It showed abnormal increased uptake of the renal graft, associated with hypermetabolic lymph nodes and hepatic, pulmonary and bone lesions. Emergency graft resection was performed 5 days after PET/CT, permitting immunosuppressive therapy withdrawal. Pathologic examination of the kidney showed parenchymal infiltration by tumor cells compatible with small cell lung cancer. Thereafter, pathologists proved that the recipient's and donor's tumor cells matched using microsatellite markers. FDG-PET/CT was performed in the follow-up and showed progression in the donor despite chemotherapy and radiotherapy. He died a few months later. However, FDG-PET/CT showed a complete metabolic response after only 3 courses of chemotherapy in the recipient.
Asunto(s)
Trasplante de Células , Fluorodesoxiglucosa F18 , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/terapia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Carcinoma Pulmonar de Células Pequeñas/diagnóstico por imagen , Carcinoma Pulmonar de Células Pequeñas/terapia , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Immunosuppressive drugs are used in the treatment of inflammatory and autoimmune diseases, as well as in transplantation. Frequently prescribed in young people, these treatments may have deleterious effects on fertility, pregnancy outcomes and the unborn child. This review aims to summarize the main gonadal side effects of immunosuppressants, to detail the effects on fertility and pregnancy of each class of drug, and to provide recommendations on the management of patients who are seen prior to starting or who are already receiving immunosuppressive treatment, allowing them in due course to bear children. The recommendations for use are established with a rather low level of proof, which needs to be taken into account in the patient management. Methotrexate, mycophenolate, and le- and teri-flunomide, cyclophosphamide, mitoxanthrone are contraindicated if pregnancy is desired due to their teratogenic effects, as well as gonadotoxic effects in the case of cyclophosphamide. Anti-TNF-alpha and mTOR-inhibitors are to be used cautiously if pregnancy is desired, since experience using these drugs is still relatively scarce. Azathioprine, glucocorticoids, mesalazine, anticalcineurins such as cyclosporine and tacrolimus, ß-interferon, glatiramer-acetate and chloroquine can be used during pregnancy, bearing in mind however that side effects may still occur. Experience is limited concerning natalizumab, fingolimod, dimethyl-fumarate and induction treatments. Conclusion: At the time of prescription, patients must be informed of the possible consequences of immunosuppressants on fertility and of the need for contraception. Pregnancy must be planned and the treatment modified if necessary in a pre-conception time period adapted to the half-life of the drug, imperatively in relation with the prescriber of the immunosuppressive drugs.