Factores de riesgo asociados al desarrollo de bacteriemia en pacientes adultos cirróticos hospitalizados

Introducción: La Bacteriemia en pacientes cirróticos es una causa importante de morbimortalidad, en gran parte favorecida por la especial vulnerabilidad de esta población ante procesos infecciosos. El objetivo fue determinar los factores asociados al desarrollo de bacteriemia primaria y secundaria en pacientes con Cirrosis, hospitalizados en la Fundación Cardioinfantil – Instituto de Cardiología entre 01 enero de 2010 y 31 enero de 2016. Materiales y Métodos: Estudio de casos y controles en pacientes mayores de 18 años con cirrosis hepática conocida o confirmada durante la hospitalización. Se realizó un análisis descriptivo, un análisis bivariado para determinar las diferencias entre los casos y los controles con respecto a las variables independientes un análisis de asociación mediante un modelo de regresión logística no condicional con variable dependiente bacteriemia. Los resultados se expresan en odds ratios con intervalos de confianza al 95%. Resultados: Las condiciones asociadas a bacteriemia como factores de riesgo fueron: Enfermedad renal crónica OR 9,1 (IC 95% 2,4-34), Escala Meld > 10 puntos OR 4,0 (IC 95% 2,-34), Infección previa OR 7,2 (IC 95% 2,1-24), presencia de catéter central OR 12,0 (IC 95% 1,8-80), presencia de sonda vesical OR 21,1 (IC 95% 1,6-276), estudio endoscópico OR 3,9 (IC 95% 1,1-14). Discusión: Factores relacionados con las condiciones clínicas del paciente evaluadas por las escalas Meld y Child-Pugh, el antecedente de infección previa y la presencia de dispositivos para monitorear el estado del paciente aumentan el riesgo de bacteriemia en pacientes hospitalizados con cirrosis.

Impacto de la implementación de un modelo de gestión integral de atención de la enfermedad y cuidado coordinado en la población en diálisis en Colombia

La atención hospitalaria en el costo global de la atención de los pacientes en diálisis es muy importante. Este estudio se realizó con el fin de evaluar resultados posteriores a la implementación de un modelo de gestión de la enfermedad y cuidado coordinado en una red de diálisis en Colombia, evaluando los cambios específicos en las tasas de hospitalización de una cohorte de pacientes renales con dos años de seguimiento. El modelo se enfoca básicamente en mejorar la atención de los pacientes en diálisis protocolizando en el manejo de comorbilidades (diabetes, riesgo cardiovascular, patologías infecciosas) y en el cuidado coordinado entre el tratamiento ambulatorio y hospitalario de los pacientes en diálisis asegurando la continuidad en el proceso de atención de los pacientes. El Estudio observacional analítico de cohortes compuesto por 2 fases una primera cohorte histórica retrospectiva y una segunda con dos cohortes prospectivas, incluyó pacientes mayores de 18 años, con más de 90 días en diálisis, con al menos tres meses de intervención con el modelo de gestión de enfermedad en la red Renal Therapy Services (RTS®). En conclusión, la realización de este estudio, se pudo asociar a la reducción en la atención hospitalaria de pacientes en diálisis y a una menor mortalidad, modelos como este y otras soluciones para mejorar los desenlaces en salud en los pacientes en diálisis deben seguir siendo implementados para aliviar la carga de la enfermedad y reducir los costos de la atención en salud de esta población.

Impacto de los Niveles de Tacrolimus en el Rechazo al Injerto y la Tasa de Filtración Glomerular en Pacientes con Trasplante Hepático realizado en la FCI-IC entre 2009 y 2014

Introducción: El tacrolimus es el medicamento de elección para evitar el rechazo al injerto hepático. Su dosis se ajusta a partir de los niveles séricos que se toman periódicamente para asegurar rango terapéutico. Además, niveles elevados se asocian con disfunción renal postrasplante. Sin embargo, no hay consenso frente a los niveles adecuados para pacientes con trasplante hepático. Objetivo: Determinar la relación entre los niveles de tacrolimus y la presencia de rechazo agudo al injerto hepático en pacientes con trasplante hepático realizado en la Fundación Cardioinfantil – Instituto de Cardiología (FCI-IC). Determinar la relación entre los niveles de tacrolimus y la TFG en pacientes con trasplante hepático realizado en la FCI-IC. Métodos: Estudio observacional tipo cohorte histórica en pacientes adultos con trasplante hepático realizado en la FCI-IC entre 2009-2014. Resultados: No se encontró una asociación estadísticamente significativa entre los niveles de tacrolimus y la presencia de rechazo agudo, en sus diferentes definiciones (OR=1,02, p=0,14 y OR=1,01, p=0,29) incluso al ajustar por otras covariables (OR=1,03, p=0,10 y OR=1,02, p=0,25). No fue posible corroborar el diagnóstico con biopsia porque no todos la tenían. Si bien la relación entre los niveles de tacrolimus y la TFG fue estadísticamente significativa (p≤0,001), tiene bajo impacto clínico, pues la TFG disminuyó menos de un punto por cada incremento en 1 ng/ml en los niveles de tacrolimus. Conclusiones: Se necesitan más estudios para establecer la relación entre la exposición a tacrolimus y estos desenlaces para definir si es seguro disminuir su dosis con el fin de reducir los eventos adversos.

Tratamiento del rechazo mediado por anticuerpos en pacientes trasplantados renales revisión sistemática

Antecedentes: El trasplante renal es la mejor alternativa terapéutica para la enfermedad renal crónica terminal. Los medicamentos inmunosupresores previenen el rechazo. El rechazo mediado por anticuerpos es frecuente y disminuye la función y duración del injerto. Objetivo: Evaluar sistemáticamente la evidencia disponible relacionada con la eficacia y seguridad del tratamiento para el rechazo mediado por anticuerpos en pacientes trasplantados renales. Metodologia: Revisión sistemática en bases de datos MEDLINE, EMBASE, Scopus y Biblioteca virtual de la salud. Literatura gris google scholar, google academico, www.clinicaltrialsregister.eu, and https://clinicaltrials.gov/. Búsqueda manual referencias artículos pre-seleccionados así como de revisiones previamente publicadas. Se siguieron las recomendacioes guia PRISMA para la identificacion de artículos potenciales, tamizaje y selección teniendo en cuenta los criterios de inclusion. Extracción datos de acuerdo a las variables, revisión calidad de los artículos elegidos utilizando evaluación riesgo de segos de Cochrane. Resultados: Se seleccionaron 9 ensayos clínicos publicados entre 1980 y 2016, incluyeron 222 pacientes (113 brazo de intervención y 109 en el control), seguimiento promedio 16 meses. Intervenciones evaluadas plasmaféresis, inmunoadsorción y rituximab. Hubo una amplia heterogeneidad en la definición de criterios de inclusión, criterios diagnósticos de rechazo y medidas de evaluación de eficacia de las intervenciones. Tres estudios encontraron diferencias estadísticamente significativas entre los grupos de tratamiento. Conclusiones: La evidencia sobre la eficacia de los tratamientos del rechazo mediado por anticuerpos en injertos renales es de baja calidad. Son necesarios ensayos clínicos controlados para poder definir el tratamiento óptimo de estos pacientes.

Clínica de animais de companhia

O presente relatório pretende descrever as atividades desenvolvidas durante o estágio curricular, realizado no Hospital Veterinário do Restelo, no período de 4 de agosto a 31 de janeiro. A hipertensão sistémica é uma doença insidiosa e progressiva, que se não controlada pode provocar lesões irreversíveis em órgãos alvo. Nos animais o seu desenvolvimento é normalmente secundário a processos de doença ou à administração exógena de alguns fármacos. Nos cães as causas mais comuns compreendem a doença renal crónica, a doença renal aguda e o hiperadrenocorticismo, enquanto nos gatos o seu desenvolvimento está, normalmente, associado à doença renal crónica, ao hipertiroidismo e ao hiperaldosteronismo primário. O diagnóstico da hipertensão e da causa primária responsável pelo seu desenvolvimento constituem um desafio clínico, criado por um conjunto diversificado de fatores associados aos animais, aos métodos de medição indiretos, processos de doença concorrentes e financeiros; Abstract: Small animal clinics The present report aims to describe the activities developed during the traineeship realized at Hospital Veterinário do Restelo, from August 4 to January 31. Systemic hypertension is an insidious and progressive disease, which uncontrolled is responsible for irreversible damage in target organs. In animals, their development is usually secondary to disease processes or exogenous administration of some drugs. In dogs, the most common causes include chronic kidney disease, acute renal disease and hyperadrenocorticism, while in cats their development is usually associated with chronic kidney disease, hyperthyroidism and primary aldosteronism. The diagnosis of hypertension and the primary cause responsible for its development are a clinical challenge created by a diverse set of factors associated with the animals, the indirect measurement methods, concurrent disease processes and financial.

Clínica de animais de companhia

A clínica veterinária de pequenos animais é um mundo vasto e complexo que necessita de um estudo contínuo. Este relatório de estágio está dividido em duas partes. A primeira parte contém a descrição das atividades realizadas durante o estágio curricular realizado na clínica AlcabidecheVet. A segunda parte corresponde a uma monografia cujo tema é doença renal crónica em animais de companhia. A doença renal crónica acomete tanto cães como gatos em idade avançada, tendo uma progressão irreversível. Vários estudos científicos têm sido realizados para melhorar a sua prevenção e diagnóstico, como o estudo de biomarcadores da função renal. A utitilização de biomarcadores no diagnóstico e controlo da doença renal é essencial para o seu estadiamento e para demarcar o avanço dos danos renais. É também necessário conhecer os mecanismos patológicos em ação nesta doença para que o seu tratamento e monitorização providenciem o máximo bem-estar e o prolongamento da vida do animal; Abstract: (Small Animal Practice and Surgery – Kidney Chronic Disease) The world of small animal veterinary practice is vast and complex and needs a continuous study. This report is divided in two parts. The first describes the activities performed during the curricular internship at the clinic AlcabidecheVet. The second consists of a monograph which theme is chronic kidney disease. Chronic kidney disease affects both dogs and cats of declining age, and has an irreversible progression. There’s been scientific advances in its prevention and diagnosis with the study of biomarkers of kidney function. It’s also necessary to understand the pathological mechanisms in action in this disease, so its treatment and control can aim towards the welfare and the life extension of pets.

Valutazione della concordanza e della capacità predittiva degli score prognostici per la definizione di rapida progressione della malattia renale conica nei pazienti con malattia policistica epato renale. Analisi di una coorte multicentrica.

Introduzione: La malattia policistica autosomica dominante (ADPKD) è una causa comune di malattia renale terminale (ESKD). È caratterizzata dallo sviluppo di cisti renali bilaterali che aumentano progressivamente di volume. Il Tolvaptan viene prescritto in base a 3 criteri: volume renale totale (HtTKV) e Mayo Clinic Imaging Class (MCIC), tasso di declino dell'eGFR e al Predicting Renal Outcome in Polycystic Kidney Disease (PROPKD), che combina variabili cliniche e genetiche. In questa coorte multicentrica retrospettiva, l'obiettivo era di valutare e migliorare la concordanza di sensibilità e specificità predittive di MCIC e PROPKD. Metodi: I dati di pazienti adulti affetti da ADPKD sono stati ottenuti da 2 centri di Bologna (B) e Dublino (D). Abbiamo definito RP un calo dell'eGFR ≥3 mL/min/1,73m2/anno su 4 anni (Clinical Score), o classi MCIC 1C-D-E, o punteggio PROPKD da 7 a 9. Per i parametri clinici sono state utilizzate statistiche descrittive. La concordanza tra i punteggi è stata valutata tramite la statistica Kappa. Nelle varianti missenso di PKD1, il punteggio REVEL è stato trattato come una variabile continua; (>0,65 patogeno'). Risultati: Abbiamo valutato 201 pazienti con ADPKD. Il Propkd e il MCIC erano rispettivamente: 90% specifico e 31,3% sensibile; 89,6% sensibile e 28,6% specifico per identificare il calo dell'eGFR. Kappa di Cohen era di 0,025. Il 47,9% (n=143) è risultato concorde. Il punteggio Revel applicato alle mutazioni PKD1NT identifica da 15 a 19 pazienti che potrebbero avere una RP. L'analisi multivariata mostra dati statisticamente significativi per HB (p:0,016), eventi urologici (p: 0,005) e MCIC (p: 0,074). Conclusioni: La concordanza tra i punteggi risulta bassa. Il PROPKD è più selettivo rispetto al Mayo. Tuttavia, il PROPKD permette di identificare alcune RP escluse dall'uso del solo MCIC. L'uso combinato dei punteggi può aumentare la capacità di identificare le RP. Il punteggio REVEL potrebbe migliorare questa concordanza

Hypertensive disorders of pregnancy and long-term cardiovascular health and outcomes

Introduction The maternal vasculature undergoes significant adaptations during pregnancy to meet the increased metabolic demands of the developing fetus. These adaptations include increased cardiac output and blood volume, as well as reduced systemic vascular resistance. In Hypertensive disorders of pregnancy (HDP) there is an impaired cardiovascular adaptation to pregnancy with effects extending beyond pregnancy. In the present study we aimed to characterize long-term cardiovascular status of women who suffered from HDP. Methods Fifty-eight women who attended at least one post-partum visit and a follow-up visit after at least 5 years from delivery were enrolled in the study. Exclusion criteria included multiple pregnancy, fetal genetic or congenital abnormalities, maternal history of organ transplantation, or chronic renal failure (eGFR≤45ml/min/1.73m2). In the follow-up visit participants underwent a complete cardiovascular assessment including echocardiography and multiparametric vascular function assessment. Results and Discussion Two major cardiovascular events, one stroke and one myocardial infarction, occurred both in women with index-pregnancy complicated by preeclampsia (PE). While not statistically significant, women with HDP-non-PE and PE displayed a trend towards an increased risk of developing composite cardiovascular outcome, and women with PE tended to experience it sooner. Nearly half of the women with a history of HDP, whether PE or HDP-non-PE, developed chronic hypertension. Some women also developed hyperuricemia, chronic kidney disease (CKD), and type 2 diabetes at follow- up, most of them had a previous history of PE. Structural and functional cardiac changes were observed in a few cases, especially among women with PE, and vascular dysfunction was more common in women with a history of HDP compared to those with normotensive pregnancies. Results of the present study adds on literature on long-term cardiovascular impact of HDP and further emphasize the importance of a timely follow-up of women who suffered from HDP and particularly PE.

Mesenchymal Stem Cells Delivered at the Subcapsule of the Kidney Ameliorate Renal Disease in the Rat Remnant Kidney Model

Stem cells (SC) are potential therapeutic tools in the treatment of chronic renal diseases. Number and engraftment of SC in the injured sites are important for possible differentiation into renal cells and paracrine effect. The aim of this study was to analyze the effect of subcapsular injection of mesenchymal stem cells (MSC) in the 5/6 nephrectomy model (5/6 Nx). MSC obtained from Wistar rats were isolated by their capacity to adhere to plastic surfaces, characterized by flow cytometry, and analyzed by their differentiation potential into osteoblasts. MSC (2 X 105) were injected into the subcapsule of the remnant kidney of male Wistar rats, and were followed for 15 or 30 days. 5/6 Nx rats showed significant hypertension at 15 and 30 days, which was reduced by MSC at 30 days. Increased albuminuria and serum creatinine at 15 and 30 days in 5/6 Nx rats were also reduced by subcapsular injection of MSC. We also observed a significant reduction of glomerulosclerosis index 30 days after injection of MSC. 4-6 diamidino-2-phenylindole dihydrochloride (DAPI)-stained MSC showed a migration of these cells into renal parenchyma 5, 15, and 30 days after subcapsular injection. In conclusion, our data demonstrated that subcapsular injection of MSC in 5/6 Nx rats is associated with renoprotective effects. These results suggest that locally implanted MSC in the kidney allow a large number of cells to migrate into the injured sites and demonstrate that subcapsular injection represent an effective route for MSC delivery.

Mild chronic kidney dysfunction and treatment strategies for stable coronary artery disease

Objective: Our objective was to evaluate the association of chronic kidney dysfunction in patients with multi-vessel chronic coronary artery disease, preserved left ventricular function, and the possible interaction between received treatment and cardiovascular events. Methods: The glomerular filtration rate was determined at baseline on 611 patients who were randomized into three treatment groups: medical treatment, percutaneous coronary intervention, and coronary artery bypass surgery. Incidence of myocardial infarction, angina requiring a new revascularization procedure, and death were analyzed during 5 years in each group. Results: Of 611 patients, 112 (18%) were classified as having normal renal function, 349 (57%) were classified as having mild dysfunction, and 150 (25%) were classified as having moderate dysfunction. There were significant differences among the cumulative overall mortality curves among the three renal function groups. Death was observed more frequently in the moderate dysfunction group than the other two groups (P < .001). Interestingly, in patients with mild chronic kidney dysfunction, we observed that coronary artery bypass treatment presented a statistically higher percentage of event-free survival and lower percentage of mortality than did percutaneous coronary intervention or medical treatment Conclusions: Our results confirm that coronary artery disease accompanied by chronic kidney dysfunction has a worse prognosis, regardless of the therapeutic strategy for coronary artery disease, when renal function is at least mildly impaired. Additionally, our data suggest that the different treatment strategies available for stable coronary artery disease may have differential beneficial effects according to the range of glomerular filtration rate strata.

HLA polymorphisms as incidence factor in the progression to end-stage renal disease in Brazilian patients awaiting kidney transplant

Chronic renal failure (CRF) leads in the majority of instances to end-stage renal disease (ESRD) requiring renal replacement therapy. Age, gender, genetics, race, hypertension, and smoking among others are factors associated with ESRD. Our interest was to evaluate the possible associations of class I and II HLA antigens with ESRD renal disease independent of other factors, among patients with CRF, having various diagnoses in the Brazilian population of the Sao Paulo state. So 21 HLA-A, 31 HLA-B, and 13 HLA-DR were detected in 105 patients who were compared with 160 healthy controls of both sexes who were not related to the patients evaluated until 2005. We calculated allelic frequencies, haplotypes frequencies, etiological fractions (EF), preventive fractions, and relative risks (RR). We compared demographic data of patients and controls. The antigens positively associated with ESRD were: HLA-A78 (RR = 30.31 and EF = 0.96) and HLA-DR11 (RR = 18.87 and EF = 0.65). The antigens HLAB14 (RR = 29.90 and EF = 0.75) was present at a significantly lower frequency among patients compared with controls. In contrast, no haplotype frequency showed statically significant associations. Further molecular studies may clarify types and subtypes of alleles involved with ESRD progression.

Mineral and Bone Disease (MBD) on a Kidney Transplant Patient

A 50-year-old post-menopausal recipient of a kidney allograft with bone pain, osteoporosis, persistent hypercalcaemia and elevated parathormone (PTH) levels, despite a satisfactory graft function, was treated with bisphosphonates and cinacalcet starting, respectively, 5 and 6 months after renal transplantation (RT). Sixteen months after treatment, there was improvement of bone mineral density (BMD) measured by dualenergy X-ray absorptiometry (DEXA). A bone biopsy was taken, unveiling a surprising and worrisome result. Post-RT bone disease is different from classic CKD-MBD and should be managed distinctly, including, in some difficult cases, an invasive evaluation through the performance of a bone biopsy, as suggested in the KDIGO guidelines.

Ganciclovir Exposure under a 450 mg Daily Dosage of Valganciclovir for the Prevention of Cytomegalovirus Disease in Kidney Transplant Recipients.

Background: It is suggested that a low dose of valganciclovir can be equally effective than a standard dose for cytomegalovirus (CMV) prophylaxis after kidney transplantation. The aim of our study was to determine the ganciclovir exposure observed under a routine daily dosage of 450 mg valganciclovir in kidney transplant recipients with a wide range of renal function. Methods: In this prospective study, kidney transplant recipients with a GFR MDRD above 25 mL/min at risk for CMV (donor or recipient seropositive for CMV) received a dose of valganciclovir (450 mg daily) prophylaxis for 3 months. Ganciclovir levels at trough (Ctrough) and at peak (C3h) were measured monthly. Ganciclovir exposure (AUC0-24) was estimated using Bayesian non-linear mixed-effect modelling (NONMEM) and compared between 3 groups of patients according to their kidney function: GFRMDRD 26-39 mL/min (Group 1), GFRMDRD 40-59 mL/min (Group 2) and GFRMDRD 60-90 mL/min (Group 3). CMV DNAemia was assessed during and after prophylaxis using PCR. Results: Thirty-six patients received 450 mg daily of valganciclovir for 3 months. Median ganciclovir C3h was 3.9 mg/L (range: 1.3-7.1) and Ctrough was 0.4 mg/L (range 0.1-2.7). Median (range) AUC0-24 of ganciclovir was 59.3 mg.h/L (39.0-85.3) in Group 1 patients, 35.8 mg.h/L (24.9-55.8) in Group 2 patients and 29.6 mg.h/L (22.0- 43.2) in Group 3 patients (p<0.001). Anemia was more common in Group 1 patients compared to patients on the other groups (p=0.01). No differences in other adverse events according to ganciclovir exposure were observed. CMV DNAemia was not detected during prophylaxis. After discontinuing prophylaxis, CMV DNAemia was seen in 8/34 patients (23.5%) and 4/36 patients (11%) developed CMV disease. Conclusion: A routine dosage of valganciclovir achieved plasma levels of ganciclovir in patients with GFR>60 mL/min similar to those previously reported using oral ganciclovir. A daily dose of 450 mg valganciclovir appears to be acceptable for CMV prophylaxis in most kidney transplant recipients.

Kidney transplantation in patients with Fabry disease

Introduction and Aims: Fabry disease is an X-linked lysosomal storage disorder caused by absence or deficient activity of the lysosomal enzyme alpha-galactosidase A. Renal manifestations occur early in life in a significant proportion of children, in many women and in almost all men with Fabry disease. These manifestations ultimately progress to end-stage renal disease in nearly all males and in some female patients. Data on kidney transplantation in patients with Fabry disease who are receiving enzyme replacement therapy (ERT), however, are scarce. Methods: We examined the clinical characteristics of kidney transplant recipients (KTRs) in the Fabry Outcome Survey (FOS) - a European database of patients with Fabry disease that was established to monitor the safety and outcome of ERT. Results: Of the 752 patients enrolled in FOS up to October 2005, 34 (4.5%) were reported to be KTRs. The mean age of these 32 male and 2 female patients was 45 ± 9 years, the median time since the transplant was 9 years, the median estimated glomerular filtration rate (eGFR) was 46 mL/min/1.73 m2 and the median level of proteinuria was 180 mg/24 hours. ERT was well tolerated, with mild infusion-related reactions reported in only one patient. Amongst these patients, 53% were reported to have hypertension, 71% left ventricular hypertrophy, 27% cardiac valve disease and 27% arrhythmia. A total of 23 (68%) of the patients (1 female, 22 males) were receiving ERT with agalsidase alfa (Replagal; Shire Human Genetic Therapies, UK), with a median duration of treatment of 2.5 years. There were no differences in age or time since transplantation between treated and untreated patients. The median eGFRs were 46 and 49 mL/min/1.73 m2 and the median levels of proteinuria were 200 and 160 mg/24 hours, respectively. Conclusions: KTRs represent a significant minority of individuals enrolled in a large international registry of patients with Fabry disease (FOS). Approximately two-thirds of KTRs with Fabry disease enrolled in FOS receive ERT with agalsidase alfa, which is well tolerated. Comparison of treated and untreated patients has the potential to examine effects of ERT on the progression of renal and cardiovascular disease.