A prospective study of hepatitis B virus markers in patients with chronic HBV infection from Brazilian families of Western and Asian origin

The purpose of the present study was to determine the frequency of hepatitis B virus (HBV) markers in families of HBsAg-positive patients with chronic liver disease. Serum anti-HBc, HBsAg and anti-HBs were determined by enzyme immunoassay and four subpopulations were considered: genetically related (consanguineous) and non-genetically related (non-consanguineous) Asian subjects and genetically related and non-genetically related Western subjects. A total of 165 and 186 relatives of Asian and Western origin were enrolled, respectively. The occurrence of HBsAg and anti-HBs antibodies was significantly higher (P < 0.0001) in family members of Asian origin (81.8%) than in family members of Western origin (36.5%). HBsAg was also more frequent among brothers (79.6 vs 8.5%; P < 0.0001), children (37.9 vs 3.3%; P < 0.0001) and other family members (33.9 vs 16.7%; P < 0.0007) of Asian than Western origin, respectivelly. No difference between groups was found for anti-HBs, which was more frequently observed in fathers, spouses and other non-genetic relatives. HBV infection was significantly higher in children of Asian than Western mothers (P < 0.0004). In both ethnic groups, the mothers contributed more to their children's infection than the fathers (P < 0.0001). Furthermore, HBsAg was more frequent among consanguineous members and anti-HBs among non-consanguineous members. These results suggest the occurrence of vertical transmission of HBV among consanguineous members and probably horizontal sexual transmission among non-consanguineous members of a family cluster. Thus, the high occurrence of dissemination of HBV infection characterizes family members as a high-risk group that calls for immunoprophylaxis. Finally, the study showed a high familial aggregation rate for both ethnic groups, 18/19 (94.7%) and 23/26 (88.5%) of the Asian and Western origin, respectively.

Proteomic inventory of myocardial proteins from patients with chronic Chagas' cardiomyopathy

Chronic Chagas' disease cardiomyopathy (CCC) is an often fatal outcome of Trypanosoma cruzi infection, with a poorer prognosis than other cardiomyopathies. CCC is refractory to heart failure treatments, and is the major indication of heart transplantation in Latin America. A diffuse myocarditis, plus intense myocardial hypertrophy, damage and fibrosis, in the presence of very few T. cruzi forms, are the histopathological hallmarks of CCC. To gain a better understanding of the pathophysiology of CCC, we analyzed the protein profile in the affected CCC myocardium. Homogenates from left ventricular myocardial samples of end-stage CCC hearts explanted during heart transplantation were subjected to two-dimensional electrophoresis with Coomassie blue staining; protein identification was performed by MALDI-ToF mass spectrometry and peptide mass fingerprinting. The identification of selected proteins was confirmed by immunoblotting. We demonstrated that 246 proteins matched in gels from two CCC patients. They corresponded to 112 distinct proteins. Along with structural/contractile and metabolism proteins, we also identified proteins involved in apoptosis (caspase 8, caspase 2), immune system (T cell receptor ß chain, granzyme A, HLA class I) and stress processes (heat shock proteins, superoxide dismutases, and other oxidative stress proteins). Proteins involved in cell signaling and transcriptional factors were also identified. The identification of caspases and oxidative stress proteins suggests the occurrence of active apoptosis and significant oxidative stress in CCC myocardium. These results generated an inventory of myocardial proteins in CCC that should contribute to the generation of hypothesis-driven experiments designed on the basis of the classes of proteins identified here.

Adherence to drug therapy in kidney disease

Non-adherence to drug therapy has not been extensively studied in patients with chronic kidney disease (CKD). The objective of the present study was to identify determinants of non-adherence to drug therapy in patients with CKD, not on dialysis. A prospective cohort study involving 149 patients was conducted over a period of 12 months. Adherence to drug therapy was evaluated by the self-report method at baseline and at 12 months. Patients who knew the type of drug(s) and the respective number of prescribed pills in use at the visit preceding the interview were considered to be adherent. Patients with cognitive decline were assessed by interviewing their caregivers. Mean patient age was 51 ± 16.7 years. Male patients predominated (60.4%). Univariate analysis performed at baseline showed that non-adherence was associated with older age, more pills taken per day, worse renal function, presence of coronary artery disease, and reliance on caregivers for the administration of their medications. In multivariate analysis, the factors that were significantly associated with non-adherence were daily use of more than 5 pills and drug administration by a caregiver. Longitudinal evaluation showed an increase in non-adherence over time. Medication non-adherence was lower (17.4%) at the baseline period of the study than after 1 year of the study (26.8%). Compared to the baseline period, the percentage of adherent patients who became non-adherent (22%) was lower than the percentage of non-adherent patients who became adherent (50%). In CKD patients not on dialysis, non-adherence was significantly associated with the number of pills taken per day and drug administration by third parties. Adherence is more frequent than non-adherence over time.

Evaluation of renal function in sickle cell disease patients in Brazil

The objective of this study was to investigate renal function in a cohort of 98 patients with sickle cell disease (SCD) followed up at a tertiary hospital in Brazil. Clinical and laboratory characteristics at the time of the most recent medical examination were analyzed. Renal function was evaluated by the estimation of glomerular filtration rate (GFR) by the criteria of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). We compared patients with normal GFR to patients with decreased GFR (<60 mL·min-1·(1.73 m²)-1) and hyperfiltration (>120 mL·min-1·(1.73 m²)-1). Comparison between patients according to the use of hydroxyurea and comparison of clinical and laboratory parameters according to GFR were also carried out. Average patient age was 33.8 ± 13.3 years (range 19-67 years), and 57 (58.1%) patients were females. The comparison of patients according to GFR showed that patients with decreased GFR (<60 mL·min-1·(1.73 m²)-1) were older, had lower levels of hematocrit, hemoglobin and platelets and higher levels of urea and creatinine. Independent risk factors for decreased GFR were advanced age (OR = 21.6, P < 0.0001) and anemia (OR = 39.6, P < 0.0001). Patients with glomerular hyperfiltration tended to be younger, had higher levels of hematocrit, hemoglobin and platelets and lower levels of urea and creatinine, with less frequent urinary abnormalities. Hydroxyurea, at the dosage of 500-1000 mg/day, was being administered to 28.5% of the patients, and there was no significant difference regarding renal function between the two groups. Further studies are required to establish the best therapeutic approach to renal abnormalities in SCD.

Assessment of indicators of vitamin A status in non-cirrhotic chronic hepatitis C patients

Subjects with chronic liver disease are susceptible to hypovitaminosis A due to several factors. Therefore, identifying patients with vitamin deficiency and a requirement for vitamin supplementation is important. Most studies assessing vitamin A in the context of hepatic disorders are conducted using cirrhotic patients. A cross-sectional study was conducted in 43 non-cirrhotic patients with chronic hepatitis C to evaluate markers of vitamin A status represented by serum retinol, liver retinol, and serum retinol-binding protein levels. We also performed the relative dose-response test, which provides an indirect estimate of hepatic vitamin A reserves. These vitamin A indicators were assessed according to the stage of liver fibrosis using the METAVIR score and the body mass index. The sample study was predominantly composed of male subjects (63%) with mild liver fibrosis (F1). The relative dose-response test was <20% in all subjects, indicating vitamin A sufficiency. Overweight or obese patients had higher serum retinol levels than those with a normal body mass index (2.6 and 1.9 µmol/L, respectively; P<0.01). Subjects with moderate liver fibrosis (F2) showed lower levels of serum retinol (1.9 vs 2.5 µmol/L, P=0.01) and retinol-binding protein levels compared with those with mild fibrosis (F1) (46.3 vs 67.7 µg/mL, P<0.01). These results suggested an effect of being overweight on serum retinol levels. Furthermore, more advanced stages of liver fibrosis were related to a decrease in serum vitamin A levels.

Multiple facets of HIV-associated renal disease

HIV infection has a broad spectrum of renal manifestations. This study examined the clinical and histological manifestations of HIV-associated renal disease, and predictors of renal outcomes. Sixty-one (64% male, mean age 45 years) HIV patients were retrospectively evaluated. Clinical presentation and renal histopathology were assessed, as well as CD4 T-cell count and viral load. The predictive value of histological lesion, baseline CD4 cell count and viral load for end-stage renal disease (ESRD) or death were determined using the Cox regression model. The outcomes of chronic kidney disease (CKD) and ESRD or death were evaluated by baseline CD4 cell count. The percent distribution at initial clinical presentation was non-nephrotic proteinuria (54%), acute kidney injury (28%), nephrotic syndrome (23%), and chronic kidney disease (22%). Focal segmental glomerulosclerosis (28%), mainly the collapsing form (HIVAN), acute interstitial nephritis (AIN) (26%), and immune complex-mediated glomerulonephritis (ICGN) (25%) were the predominant renal histology. Baseline CD4 cell count ≥200 cells/mm3 was a protective factor against CKD (hazard ratio=0.997; 95%CI=0.994-0.999; P=0.012). At last follow-up, 64% of patients with baseline CD4 ≥200 cells/mm3 had eGFR >60 mL·min-1·(1.73 m2)-1 compared to the other 35% of patients who presented with CD4 <200 cells/mm3 (log rank=9.043, P=0.003). In conclusion, the main histological lesion of HIV-associated renal disease was HIVAN, followed by AIN and ICGN. These findings reinforce the need to biopsy HIV patients with kidney impairment and/or proteinuria. Baseline CD4 cell count ≥200 cells/mm3 was associated with better renal function after 2 years of follow-up.

Averting the legacy of kidney disease - focus on childhood

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, in that the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease as a consequence of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, although only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that the World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Steroid-resistant idiopathic nephrotic syndrome in children: long-term follow-up and risk factors for end-stage renal disease

INTRODUTION: Steroid resistant idiopathic nephrotic syndrome (SRINS) in children is one of the leading causes of progression to chronic kidney disease stage V (CKD V)/end stage renal disease (ESRD). OBJECTIVE: The aim of this retrospective study is to evaluate the efficacy of immunosuppressive drugs (IS) and to identify risk factors for progression to ESRD in this population. METHODS: Clinical and biochemical variables at presentation, early or late steroid resistance, histological pattern and response to cyclosporine A (CsA) and cyclophosfamide (CP) were reviewed in 136 children with SRINS. The analyzed outcome was the progression to ESRD. Univariate as well as multivariate Cox-regression analysis were performed. RESULTS: Median age at onset was 5.54 years (0.67-17.22) and median follow up time was 6.1 years (0.25-30.83). Early steroid-resistance was observed in 114 patients and late resistance in 22. Resistance to CP and CsA was 62.9% and 35% respectively. At last follow-up 57 patients reached ESRD. The renal survival rate was 71.5%, 58.4%, 55.3%, 35.6% and 28.5% at 5, 10, 15, 20 and 25 years respectively. Univariate analysis demonstrated that older age at onset, early steroid-resistance, hematuria, hypertension, focal segmental glomerulosclerosis (FSGS), and resistance to IS were risk factors for ESRD. The Cox proportional-hazards regression identified CsAresistance and FSGS as the only predictors for ESRD. CONCLUSION: Our findings showed that CsA-resistance and FSGS were risk factors for ESRD.

Vitamin D and Kidney disease: what we know and what we do not know

Vitamin D deficiency is common in the chronic kidney disease (CKD) population. CKD has been recognized as a significant public health problem and CKD patients are at increased risk of total and cardiovascular morbidity and mortality. There are increasing epidemiological data suggesting that vitamin D deficiency may play a role in overall morbidity and mortality associated with CKD. The vitamin D hormonal system is classically implicated in the regulation of calcium homeostasis and bone metabolism but there is ample evidence to support the claim that extra renal conversion of 25(OH)D to 1.25(OH)2 has significant biological roles beyond those traditionally ascribed to vitamin D. Based on the current state of evidence this review intends to give an update on novel biological and clinical insights with relevance to the steroid hormone vitamin D specifically in patients with kidney disease.

Clinical and genetic markers in disease progression – a study among subjects with obstructive lung diseases

Asthma, COPD, and asthma and COPD overlap syndrome (ACOS) are chronic pulmonary diseases with an obstructive component. In COPD, the obstruction is irreversible and the disease is progressive. The aim of the study was to define and analyze factors that affected disease progression and patients’ well-being, prognosis and mortality in Chronic Airway Disease (CAD) cohort. The main focus was on COPD and ACOS patients. Retrospective data from medical records was combined with genetic and prospective follow-up data. Smoking is the biggest risk factor for COPD and even after the diagnosis of the disease, smoking plays an important role in disease development and patient’s prognosis. Sixty percent of the COPD patients had succeeded in smoking cessation. Patients who had managed to quit smoking had lower mortality rates and less psychiatric diseases and alcohol abuse although they were older and had more cardiovascular diseases than patients who continued smoking. Genetic polymorphism rs1051730 in the nicotinic acethylcholine receptor gene (CHRNA3/5) associated with heavy smoking, cancer prevalence and mortality in two Finnish independent cohorts consisting of COPD patients and male smokers. Challenges in smoking cessation and higher mortality rates may be partly due to individual patient’s genetic composition. Approximately 50% of COPD patients are physically inactive and the proportion was higher among current smokers. Physically active and inactive patients didn’t differ from each other in regard to age, gender or comorbidities. Bronchial obstruction explained inactivity only in severe disease. Subjective sensation of dyspnea, however, had very strong association to inactivity and was also associated to low health related quality of life (HRQoL). ACOS patients had a significantly lower HRQoL than either the patients with asthma or with COPD even though they were younger than COPD patients, had better lung functions and smaller tobacco exposure.

Genes involved in the metabolism of fatty acids and risk for Crohn's disease in children: a candidate gene study

Contexte - La prévalence de la maladie de Crohn (MC), une maladie inflammatoire chronique du tube digestif, chez les enfants canadiens se situe parmi les plus élevées au monde. Les interactions entre les réponses immunes innées et acquises aux microbes de l'hôte pourraient être à la base de la transition de l’inflammation physiologique à une inflammation pathologique. Le leucotriène B4 (LTB4) est un modulateur clé de l'inflammation et a été associé à la MC. Nous avons postulé que les principaux gènes impliqués dans la voie métabolique du LTB4 pourrait conférer une susceptibilité accrue à l'apparition précoce de la MC. Dans cette étude, nous avons exploré les associations potentielles entre les variantes de l'ADN des gènes ALOX5 et CYP4F2 et la survenue précoce de la MC. Nous avons également examiné si les gènes sélectionnés montraient des effets parent-d'origine, influençaient les phénotypes cliniques de la MC et s'il existait des interactions gène-gène qui modifieraient la susceptibilité à développer la MC chez l’enfant. Méthodes – Dans le cadre d’une étude de cas-parents et de cas-témoins, des cas confirmés, leurs parents et des contrôles ont été recrutés à partir de trois cliniques de gastro-entérologie à travers le Canada. Les associations entre les polymorphismes de remplacement d'un nucléotide simple (SNP) dans les gènes CYP4F2 et ALOX5 ont été examinées. Les associations allélique et génotypiques ont été examinées à partir d’une analyse du génotype conditionnel à la parenté (CPG) pour le résultats cas-parents et à l’aide de table de contingence et de régression logistique pour les données de cas-contrôles. Les interactions gène-gène ont été explorées à l'aide de méthodes de réduction multi-factorielles de dimensionnalité (MDR). Résultats – L’étude de cas-parents a été menée sur 160 trios. L’analyse CPG pour 14 tag-SNP (10 dans la CYP4F2 et 4 dans le gène ALOX5) a révélé la présence d’associations alléliques ou génotypique significatives entre 3 tag-SNP dans le gène CYP4F2 (rs1272, p = 0,04, rs3093158, p = 0.00003, et rs3093145, p = 0,02). Aucune association avec les SNPs de ALOX5 n’a pu être démontrée. L’analyse de l’haplotype de CYP4F2 a montré d'importantes associations avec la MC (test omnibus p = 0,035). Deux haplotypes (GAGTTCGTAA, p = 0,05; GGCCTCGTCG, p = 0,001) montraient des signes d'association avec la MC. Aucun effet parent-d'origine n’a été observé. Les tentatives de réplication pour trois SNPs du gene CYP4F2 dans l'étude cas-témoins comportant 225 cas de MC et 330 contrôles suggèrent l’association dans un de ceux-ci (rs3093158, valeur non-corrigée de p du test unilatéral = 0,03 ; valeur corrigée de p = 0.09). La combinaison des ces deux études a révélé des interactions significatives entre les gènes CYP4F2, ALOX et NOD2. Nous n’avons pu mettre en évidence aucune interaction gène-sexe, de même qu’aucun gène associé aux phénotypes cliniques de la MC n’a pu être identifié. Conclusions - Notre étude suggère que la CYP4F2, un membre clé de la voie métabolique LTB4 est un gène candidat potentiel pour MC. Nous avons également pu mettre en évidence que les interactions entre les gènes de l'immunité adaptative (CYP4F2 et ALOX5) et les gènes de l'immunité innée (NOD2) modifient les risques de MC chez les enfants. D'autres études sur des cohortes plus importantes sont nécessaires pour confirmer ces conclusions.

Calidad de vida en salud en pacientes con insuficiencia venosa mixta luego de varicosafenectomia

INTRODUCCIÓN: Estudios demuestran la mejoría de la insuficiencia venosa profunda luego de realizar varicosafenectomía, la amplia brecha entre resultados positivos (30-70%) deja en cuestionamiento la realización de cirugía para esta condición. Sin embargo, la mejoría en la calidad de vida en el postoperatorio pudiera ser otra razón para realizar varicosafenectomía en pacientes con insuficiencia venosa mixta. METODOLOGÍA: Se realizó un estudio de corte transversal en pacientes con diagnóstico de insuficiencia venosa mixta llevados a varicosafenectomía. En el periodo post operatorio se practicaron encuestas de calidad de vida de tipo genérico y específico realizando un análisis uni y bivariado de dicha información mediante el programa Stata. RESULTADOS: Se obtuvieron 60 pacientes, al practicar las encuestas de calidad de vida se encontraron datos estadísticamente significativos (p 0.04) en la percepción de su salud con respecto al año anterior y escalas de las encuestas referentes a estados generales de salud como función física y vitalidad. Adicionalmente, se encontró mejoría en el estado de la piel y no se evidenciaron complicaciones tales como Tromboembolismo pulmonar o Trombosis venosa profunda. CONCLUSIONES: Los resultados del presente estudio demuestran que la mayor parte de los pacientes luego de varicosafenectomía tienen una buena percepción de calidad de vida en salud, reflejada en las altas puntuaciones en la mayoría de las escalas de la SF-36, y los bajos puntajes en el cuestionario específico de insuficiencia venosa. La mejoría en la piel de la mayoría de los pacientes en el periodo postoperatorio y la mínima presencia de complicaciones como TEP o TVP hacen que la remoción de los troncos safenos incompetentes en este tipo de pacientes pueda establecerse como indicación quirúrgica

Prevalencia de insuficiencia renal crónica en niños con displasia renal multiquística, Fundación Cardioinfantil de Bogotá

Introducción: La displasia renal multiquistica es una variante de displasia renal, anomalía congénita frecuente del tracto urinario, con una prevalencia del 2.9 - 50 % de insuficiencia renal crónica; frecuentemente asociada a otras malformaciones urinarias, sin datos en bogotá sobre prevalencia y comportamiento clínico. Objetivo: Evaluar la prevalencia de insuficiencia renal crónica en niños con displasia renal multiquistica valorados en consulta de nefrología en Fundación Cardioinfantil, instituto de cardiología de Bogotá. Metodología: Estudio de corte transversal, en niños con displasia renal multiquistica, confirmado por ecografía, valorados en consulta de Nefrología Pediátrica en los últimos diez años. Se realizó un análisis descriptivo de las variables, cálculos de prevalencia de Insuficiencia renal crónica. Resultados: Se revisó información de 70 pacientes, encontrando una prevalencia de IRC de 22.85% (IC 95 % 13.0 %-35.1 %); mayor frecuencia mujeres 12.85 %; 14.28% con otras malformaciones renales; 5.71 % en involución parcial, 4.28% en pacientes con involución completa del tamaño del riñón displásico. Se encontró 31.4% proteinuria; 22.8 % hiperfiltración; 4.28% hipertrofia compensadora del riñón sano; 24.2% involución parcial, 31.4 % involución completa del tamaño renal; frecuencia de HTA de 7,1% (IC95% 1%-9%). El 87.14% tuvo diagnóstico prenatal (IC 95% 81.0%-96.0%). Discusión: La prevalencia se encuentra dentro de los rangos de la literatura mundial, mayor a la colombiana y suramericana, predominando en pacientes con otras malformaciones renales asociadas, con mayor prevalencia de hipertensión arterial, que requiere estudios multicéntricos para determinar causalidad o presencia de otros factores.

Factores de riesgo para el desarrollo de complicaciones: infecciones en varicosafenectomia

La enfermedad venosa periférica de miembros inferiores se considera una de las afecciones más prevalentes, con morbilidad considerable, deterioro de la calidad de vida, e importante demanda de recursos de salud, que en la mayoría de casos requiere manejo quirúrgico como parte del tratamiento. Este estudio busca analizar si la técnica quirúrgica es un factor de riesgo, que incrementa la aparición de infección de sitio quirúrgico en 257 pacientes a quienes se les realizó varicosafenectomia. Metodología: Se realizó un estudio de cohorte retrospectiva; se recolectaron los datos a partir de los registros clínicos y quirúrgicos de pacientes que cumplieron con los criterios de inclusión, registrando factores de riesgo, descripción quirúrgica, complicaciones, y evolución post operatoria hasta 8 semanas. El análisis estadístico se realizó mediante el cálculo de riesgo relativo y regresión logística binomial. Resultados: Se demostró asociación entre la presencia de infección de sitio quirúrgico y tipo de cirugía con un RR = 3,05 (P= 0,01), clasificación CEAP con 29% menos riesgo en varicosafenectomia total (P= 0,008). Conclusiones: Existen variables clínicas y quirúrgicas que influyen en la probabilidad de desarrollar infección del sitio quirúrgico.

Accesos vasculares para hemodiálisis, cuál es el más costo efectivo?

Marco conceptual: La enfermedad renal crónica es un serio problema de salud pública en nuestro país por la gran cantidad de recursos económicos que requiere su atención. La hemodiálisis es el tratamiento más usado en nuestro medio; el acceso vascular y sus complicaciones derivadas son el principal aspecto que incrementa los costos de atención en éstos pacientes. Materiales y métodos: Se realizó un estudio económico de los accesos vasculares en pacientes incidentes de hemodiálisis en el año 2012 en la agencia RTS-Fundación Cardio Infantil. Se estableció el costo de creación y mantenimiento del acceso con catéter central, fístula arteriovenosa nativa, fístula arteriovenosa con injerto; y el costo de atención de las complicaciones para cada acceso. Se determinó la probabilidad de ocurrencia de complicaciones. Mediante un árbol de decisiones se trazó el comportamiento de cada acceso en un período de 5 años. Se establecieron los años de vida ajustados por calidad (QALY) en cada acceso y el costo para cada uno de éstos QALY. Resultados: de 36 pacientes incidentes de hemodiálisis en 2012 el 100% inició con catéter central, 16 pacientes cambiaron a fístula arteriovenosa nativa, 1 a fístula arteriovenosa con injerto que posteriormente pasó a CAPD, 15 continuaron su acceso con catéter y 4 pacientes fallecieron. En 5 años se obtuvieron 2,36 QALY para los pacientes con catéter central que costarían $ 24.813.036,39/QALY y 2,535 QALY para los pacientes con fístula nativa que costarían $ 6.634.870,64/QALY. Conclusiones: el presente estudio muestra que el acceso vascular mediante fístula arteriovenosa nativa es el más costo-efectivo que mediante catéter