Relationship between hyperuricemia, HSP70 and NLRP3 inflammasome in arterial hypertension / La relación hiperuricemia-HSP70-NLRP3 inflamosoma en la hipertensión arterial

Abstract Arterial hypertension is the most important cardiovascular risk factor in chronic non-communicable diseases and is estimated to be responsible for 10.4 million deaths annually. The global prevalence of hypertension is 30% and the majority of people with hypertension do not have a clear identifiable cause and are considered to have primary hypertension. Experimental and clinical investigations from several research groups, including ours, have established that inflammation and autoimmune reactivity play a role in the sodium retention and hemodynamic responses that drive primary hypertension. Hyperuricemia and heat stress proteins (HSP), particularly HSP70, are both associated with the activation of innate immunity that plays a role in the development of inflammatory reactivity in the hypertensive patient. Clinical studies have shown an association between the expression of HSP70 and anti-HSP70 antibodies and primary hypertension. This brief review aims to examine the interrelation between hyperuricemia and extracellular overexpression of HSP70 in the activation of the inflammasome that may have a central role in the pathophysiology of primary hypertension.

Resumen La hipertensión arterial es el factor de riesgo cardiovascular más importante de las enfermedades crónicas no transmisibles y se estima que es responsable de 10.4 millones de muertes al año. La prevalencia mundial de la hipertensión es del 30%; la mayoría de las personas con hipertensión no tienen una causa claramente identificable y se considera que tienen hipertensión primaria. Las investigaciones experimentales y clínicas de varios grupos de investigación, incluido el nuestro, han establecido que la inflamación y la reactividad autoinmune desempeñan un papel en la retención de sodio y las respuestas hemodinámicas que provocan la hipertensión primaria. La hiperuricemia y las proteínas del estrés por calor (HSP), particularmente HSP70, están asociadas con la activación de la inmunidad innata que juega un papel en el desarrollo de la reactividad inflamatoria en pacientes hipertensos. Estudios clínicos han demostrado asociación entre la expresión de HSP70 y anticuerpos anti-HSP70 y la hipertensión arterial primaria Esta breve revisión tiene como objetivo examinar la interrelación entre la hiperuricemia y la sobreexpresión extracelular de HSP70 en la activación del inflamasoma, así como su probable papel central en la fisiopatología de la hipertensión primaria.

Asociación entre uricemia y síndrome metabólico en un centro hospitalario de Corrientes / Association between uricemia and metabolic syndrome in a hospital center in Corrientes

Resumen Introducción: en los últimos años numerosa evidencia científica sugiere que la hiperuricemia puede jugar un papel en el desarrollo del síndrome metabólico (SM). En algunos estudios se ha explorado la asociación entre la uricemia y la presencia de SM. Sin embargo, aún no está del todo esclarecido si altos niveles del ácido úrico se relacionan de una manera causal con el desarrollo del SM. Más aún, existen pocos estudios acerca de la presencia del SM y su relación con los niveles de AU en la ciudad de Corrientes. Objetivos: determinar la relación de los niveles séricos de AU y los parámetros que definen el SM en pacientes que concurren al consultorio externo de Clínica Médica y Medicina General del Hospital Ángela I. de Llano, Corrientes, Argentina. Resultados: se incluyó un total de 435 pacientes mayores de 18 años: 312 mujeres (72%) y 123 hombres (28%). El 58% de la población cumplía con el criterio de SM del NCEP-ATP III (60% mujeres y 52% hombres). El 75% presentó hiperuricemia y SM. En este estudio la presencia de SM se asoció significativamente con los valores de uricemia OR: 1.5 (IC 95%: 1,3-1,8). La asociación fue estadísticamente significativa. Conclusiones: los resultados demostraron que el aumento de la frecuencia de los componentes del SM está en relación directa con el incremento de los niveles séricos de AU, y que el valor de corte para esta asociación fue de 4 mg/dl; de ahí la importancia de considerar la determinación de los niveles séricos de AU como posible predictor de SM.

Abstract Introduction: in recent years, numerous scientific evidence suggest that hyperuricemia may play a role in the development of metabolic syndrome (MS). Some studies have explored the association between uricemia and the presence of MS. However, it remains unclear whether high uric acid levels are causally related to the development of MS. Moreover, there are few studies on the presence of metabolic syndrome and its relationship with uric acid (UA) levels in the city of Corrientes, Argentina. Objectives: to determine the relationship between serum UA levels and the parameters that define MS in patients attending the outpatient clinic of Medical Clinic and General Medicine of the Ángela I. de Llano Hospital, Corrientes. Results: a total of 435 patients over 18 years of age were included: 312 (72%) women and 123 (28) men. Fifty-eight percent of the population met the NCEP-ATP III criteria for MS (60% females and 52% males). Seventy-five percent of the population had hyperuricemia and MS. In this study the presence of MS was significantly associated with uricemia values OR:1.5 (95%CI:1.3-1.8). The association is statistically significant. Conclusions: the results show that the increase in the frequency of the components of MS, goes in direct relation with the increase in serum UA levels and that the cut-off value for this association is 4 mg/dl. Hence the importance of considering the determination of serum UA levels as a possible predictor of MS.

Tofo gotoso gigante en presentación inusual / Giant gouty tophi in unusual presentation

La gota es una enfermedad reumática inflamatoria que se debe al depósito de cristales de urato monosódico en las articulaciones. En su evolución clínica se distingues dos formas: la fase aguda caracterizada por un proceso inflamatorio monoarticular agudo de gran sensibilidad, y la fase crónica o de mantenimiento, cuyo elemento fundamental es la acumulación de cristales de urato monosódico llamados tofos gotosos. Estos se presentan con mayor frecuencia en el dorso de los dedos, a nivel articular y en el pabellón auricular. Se presenta el caso de un paciente masculino, de 47 años, con diagnóstico de gota de 5 años de evolución y con tratamiento irregular. Este paciente presentó tofos gotosos en localizaciones infrecuentes que limitaron su capacidad funcional. Este caso demuestra la necesidad de un diagnóstico oportuno y una adecuada adherencia al tratamiento, por lo que se considera importante para la comunidad médica, especialmente los profesionales de la salud que atienden a pacientes con artropatía gotosa(AU)´

Gout is a rheumatic, inflammatory disease that is generated by the deposition of monosodium urate crystals at the joint level. Two forms can be distinguished in its clinical evolution: the acute phase characterized by an acute monoarticular inflammatory process of great sensitivity, and the chronic or maintenance phase where the fundamental element is the presence of accumulations of monosodium urate crystals called gouty tophi. These occur more frequently on the back of the fingers, at the joint level and in the auricle. This paper presents the case of a 47-year-old male patient, diagnosed with gout for 5 years and with irregular treatment, who presented gouty tophi in infrequent locations that limit the patient's functional capacity. The case is presented considering it important for the medical community; especially health professionals caring for patients with gouty arthropathy(AU)´

Hyperuricemia and chronic kidney disease: to treat or not to treat / Hiperuricemia e doença renal crônica: tratar ou não tratar

Abstract Hyperuricemia is common in chronic kidney disease (CKD) and may be present in 50% of patients presenting for dialysis. Hyperuricemia can be secondary to impaired glomerular filtration rate (GFR) that occurs in CKD. However, hyperuricemia can also precede the development of kidney disease and predict incident CKD. Experimental studies of hyperuricemic models have found that both soluble and crystalline uric acid can cause significant kidney damage, characterized by ischemia, tubulointerstitial fibrosis, and inflammation. However, most Mendelian randomization studies failed to demonstrate a causal relationship between uric acid and CKD, and clinical trials have had variable results. Here we suggest potential explanations for the negative clinical and genetic findings, including the role of crystalline uric acid, intracellular uric acid, and xanthine oxidase activity in uric acid-mediated kidney injury. We propose future clinical trials as well as an algorithm for treatment of hyperuricemia in patients with CKD.

Resumo A hiperuricemia é comum na doença renal crônica (DRC) e pode estar presente em até 50% dos pacientes que se apresentam para diálise. A hiperuricemia pode ser secundária ao comprometimento da taxa de filtração glomerular (TFG) que ocorre na DRC. No entanto, ela também pode preceder o desenvolvimento da doença renal e mesmo prever uma DRC incidente. Estudos experimentais de modelos hiperuricêmicos descobriram que tanto o ácido úrico solúvel quanto o cristalino podem causar danos renais significativos, caracterizados por isquemia, fibrose tubulointersticial e inflamação. Entretanto, a maioria dos estudos de randomização Mendeliana falhou em demonstrar uma relação causal entre o ácido úrico e a DRC, e os ensaios clínicos têm apresentado resultados variáveis. Aqui sugerimos explicações potenciais para os achados clínicos e genéticos negativos, incluindo o papel do ácido úrico cristalino, do ácido úrico intracelular e da atividade da xantina oxidase na lesão renal mediada por ácido úrico. Propomos ensaios clínicos futuros, bem como um algoritmo para o tratamento de hiperuricemia em pacientes com DRC.

Impacto da Concentração de Ácido Úrico Sérico no Risco de Doença Cardiovascular: Um Estudo Coorte Realizado no Norte da China / Impact of Serum Uric Acid Concentration on the Risk of Cardiovascular Disease: A Cohort Study Conducted in Northern China

Resumo Fundamento Os resultados de estudos anteriores sobre a relação entre ácido úrico sérico (AUS) e o risco de doença cardiovascular (DCV) até agora são inconsistentes devido aos fatores de confusão causados por outros fatores de risco cardiovascular conhecidos. Objetivos Este estudo tem o objetivo de avaliar a relação entre o AUS e as DCV incidentes em chineses de meia-idade e idosos, que foram estratificados de acordo com o índice de massa corporal (IMC). Métodos Recrutamos 5.721 participantes com idades entre 40 e 75 anos que não tinham diagnóstico de DCV na linha de base, e que foram monitorados de 2008 a 2017. Os participantes foram categorizados em quintis de AUS. A regressão de Cox e a análise de sobrevivência de Kaplan-Meier foram utilizadas para comparar a incidência de DCV entre os grupos de AUS. As correlações entre AUS e a incidência de DCV em grupos com IMC e circunferência de cintura (CC) variados também foram analisadas. Um P valor <0,05 foi considerado estatisticamente significativo. Resultados Durante um período médio de monitoramento de 7,6 anos, a incidência de DCV aumentou com o AUS (teste de Log-rank p<0,001). Em comparação com o primeiro quintil, as razões de risco padronizadas (intervalos de confiança de 95%) para p desenvolvimento de DCV foram 1,08 (0,78-1,65), 1,17 (0,88-1,77), 1,47 (1,12-2,21), e 1,68 (1,28-2,44) para o segundo, terceiro, quarto e quinto quintis, respectivamente. Essa relação ficou mais clara em participantes com IMC e CC normais. A razão de risco ajustada para cada aumento de 100 μmol/L de AUS foi de 1,13 (intervalo de confiança de 95%: 1,02-1,39) para eventos de DCV. Conclusões O AUS alto é um fator de risco de DCV independente em pessoas de meia-idade e idosas do norte da China. Esse efeito é mantido mesmo depois da estratificação de acordo com medidas de magreza/obesidade.

Abstract Background The results of previous studies of the relationship between serum uric acid (SUA) and the risk of cardiovascular disease (CVD) have been inconsistent due to confounding factors caused by other known cardiovascular risk factors. Objectives This study aimed to evaluate the relationship between SUA and incident CVD in middle-aged and elderly Chinese people, who were stratified according to body mass index (BMI). Methods This study recruited 5,721 participants of 40-75 years of age, who were free of CVD at baseline and who underwent follow-up from 2008 to 2017. Participants were categorized in SUA quintiles. Cox proportional hazard and Kaplan-Meier survival analysis were used to compare CVD incidence among the SUA groups. The correlations between SUA and CVD incidence in groups with differing BMI and waist circumference (WC) were also analyzed. A P value <0.05 was considered statistically significant. Results During a mean follow-up period of 7.6 years, CVD incidence increased with SUA (log-rank test p<0. 001). Compared with the first quintile, the adjusted hazard ratios (95% confidence interval (CI)) for the development of CVD were 1.08 (0.78-1.65), 1.17 (0.88-1.77), 1.47 (1.12-2.21), and 1.68 (1.28-2.44) for the second to fifth quintiles, respectively. This relationship was clearer in participants with normal BMI and WC. The adjusted hazard ratio for each 100 μmol/L increase in SUA was 1.13 (95% CI: 1.02-1.39) for CVD events. Conclusions High SUA is an independent risk factor for CVD in middle-aged and elderly northern Chinese people. This effect is maintained even after stratification according to measures of leanness/obesity.

Hipertensão arterial e ácido úrico sérico em idosos - estudo SEPHAR III / Arterial hypertension and serum uric acid in elderly- SEPHAR III study

Resumo Fundamento: A hiperuricemia é um achado frequente em pacientes com hipertensão arterial e há evidências cada vez maiores de que essa entidade seja também um fator de risco para doença cardiovascular. Objetivos: No contexto da população em processo de envelhecimento, este estudo tem o objetivo de avaliar níveis de ácido úrico sérico e a prevalência e o controle da hipertensão arterial em um subgrupo da população de adultos romenos (>65 anos), em relação à influência da idade nesses parâmetros. Métodos: A amostra do estudo consiste em 1920 adultos incluídos na pesquisa SEPHAR III, dos quais 447 eram pacientes idosos (>65 anos de idade). Durante as duas visitas do estudo, três aferições de pressão arterial (PA) foram realizadas em intervalos de 1 minuto, e foram realizadas medições de níveis de ácido úrico sérico, função renal por taxa de filtração glomerular, pressão arterial e espessura íntima-média. A hipertensão e os controles foram definidos de acordo com as diretrizes atuais. A avaliação da espessura íntima-média foi determinada pela avaliação por ultrassom Doppler modo B. Um nível de significância p < 0,05 foi adotado para a análise estatística. Resultados: Pacientes adultos tinham níveis de ácido úrico sérico significativamente mais baixos, se comparados a pacientes idosos, independentemente dos níveis de taxa de filtração glomerular. Pacientes adultos tinham níveis de espessura íntima-média, comparados a pacientes idosos. Conclusão: De forma semelhante às pesquisas anteriores, neste estudo, a idade representou um dos fatores contribuintes ao nível aumentado de ácido úrico sérico. Também foi obtido um aumento da prevalência da hipertensão arterial com a idade, com um mau controle da pressão arterial.

Abstract Background: Hyperuricemia is a frequent finding in patients with arterial hypertension, and there is increasing evidence that this entity is also a risk factor for cardiovascular disease. Objective: In the context of an aging population, this study aims to evaluate serum uric acid levels and arterial hypertension prevalence and control in a subgroup of Romanian adults (>65 years), concerning the influence of age on these parameters. Method: The study sample consists of 1,920 adults included in SEPHAR III survey, of whom 447 were elderly patients (>65 years of age). During the two study visits, three blood pressure (BP) measurements were performed at 1-min intervals and serum uric acid levels, kidney function by estimated glomerular filtration rate, blood pressure, and intima media thickness measurements were conducted. Hypertension and controls were defined according to the current guidelines. Intima-media thickness evaluation was assessed by B-mode Doppler ultrasound evaluation. A significance level p < 0.05 was adopted for the statistical analysis. Results: Adult patients had a significant lower serum uric acid levels, compared to elderly patients, regardless of glomerular filtration rate levels. Adult patients showed a significantly lower intima-media thickness levels, when compared to elderly patients. Conclusion: Similar to previous studies, in the present study, age represented one of the factors contributing to the increased level of serum uric acid. An increasing prevalence of arterial hypertension with age, together with a poor control of blood pressure, was also obtained.

Associação entre Ácido Úrico Sérico e Pré-Hipertensão e Hipertensão entre Adultos Chineses / Association between Serum Uric Acid and Pre-hypertension and Hypertension among Chinese Adults

Resumo Fundamento O ácido úrico , produto final do metabolismo dos nucleotídeos das purinas, participa dos processos de doenças metabólicas e cardiovasculares. Evidências experimentais sugerem que o ácido úrico é um mediador importante na resposta fisiológica ao aumento da pressão arterial. Objetivo Avaliar a associação entre os níveis séricos de AU e pré-hipertensão e hipertensão em uma população chinesa. Métodos Conduziu-se um estudo transversal entre março e setembro de 2017, e 1.138 participantes com idades entre 35 e 75 anos foram incluídos neste estudo, onde 223 normotensos, 316 pré-hipertensos e 599 hipertensos foram selecionados para avaliar a associação entre níveis séricos de AU e hipertensão. Considerou-se um valor de p<0,05 estatisticamente significativo. Resultados Os níveis séricos de AU foram significativamente maiores no grupo pré-hipertensão e hipertensão em comparação com o grupo controle em toda a população (p<0,05 para todos). A análise quantitativa das características indicou níveis séricos de AU (2,92±0,81, 3,06±0,85, 3,22±0,98 mg/d) linearmente aumentados em mulheres normotensas, pré-hipertensas e hipertensas, com um valor de p de 0,008. Os níveis séricos de AU nos quartis correlacionaram-se positivamente com a PAD (p<0,05), principalmente em mulheres. Após o ajuste para idade, sexo, índice de massa corporal (IMC), glicose (GLI), colesterol total (CT), triglicerídeos (TG), colesterol HDL (lipoproteína de alta densidade), as razões de chances ( odds ratios — ORs) e intervalos de confiança (IC) de 95% da pré-hipertensão, dos níveis séricos de AU mais baixos (referentes) aos mais altos foram 1,718 (1,028-2,872), 1,018 (0,627-1,654) e 1,738 (1,003-3,010). Além disso, o segundo quartil dos níveis séricos de AU esteve significativamente associado à hipertensão, com uma OR (IC 95%) de 2,036 (1,256-3,298). Conclusões O presente estudo sugere que níveis séricos mais elevados de AU estão positivamente associados à pré-hipertensão e hipertensão entre adultos chineses.

Abstract Background Uric acid (UA), the end product of purine nucleotide metabolism, participates in the processes of metabolic and cardiovascular diseases. Experimental evidence suggests it is an important mediator in the physiological response to blood pressure increase. Objective To evaluate the association between serum UA levels and pre-hypertension and hypertension in a Chinese population. Methods A cross-sectional study was conducted from March to September 2017, and 1,138 participants aged 35 to 75 were enrolled in this study, where 223 normotensive, 316 pre-hypertensive, and 599 hypertensive subjects were selected to evaluate the association between serum UA levels and hypertension. A p-value <0.05 was considered statistically significant. Results Serum UA levels were significantly higher in the pre-hypertension and hypertension group compared to the control group in the entire population (p<0.05 for all). Quantitative trait analysis indicated that serum UA levels were (2.92±0.81, 3.06±0.85, 3.22±0.98 mg/d) linearly increased in normotensive, pre-hypertensive and hypertensive females, with a p value of 0.008. Serum UA levels in the quartiles were positively correlated with DBP (p<0.05), particularly in females. After adjusting for age, gender, body mass index (BMI), glucose (GLU), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), the odds ratios (ORs) and 95% confidence intervals (CIs) of pre-hypertension from the lowest (referent) to the highest levels of serum UA were 1.718 (1.028-2.872), 1.018 (0.627-1.654) and 1.738 (1.003-3.010). Additionally, the second quartile of serum UA levels were significantly associated with hypertension, with an OR (95% CI) of 2.036 (1.256-3.298). Conclusions This study suggests that higher serum UA levels are positively associated with pre-hypertension and hypertension among Chinese adults.

Hiperuricemia em psoriase e artrite psoriática / Hyperuricemia in psoriasis and psoriatic arthritis

Introdução: A psoríase é uma doença inflamatória crônica, imunomediada, de base genética, com grande polimorfismo de expressão clínica. É caracterizada pelo envolvimento de pele, unhas e, eventualmente, articulações. De ocorrência mundial, possui prevalência entre 2 a 3% na população geral. Entre 20-30% dos pacientes com psoríase desenvolvem a artrite psoriática (AP) a qual pode preceder, estar associada ou suceder o aparecimento da psoríase. A hiperuricemia é uma condição frequentemente associada a pacientes psoriásicos. Objetivos: Estudar a prevalência de hiperuricemia em pacientes com psoríase e sua possível associação com o fenótipo da doença, atividade articular e cutânea. Metodologia: Trata-se de um estudo transversal e analítico realizado através da avaliação de ácido úrico de 58 pacientes diagnosticados com psoríase (com e sem AP) acompanhados pelos ambulatórios de dermatologia e reumatologia do Hospital Universitário Evangélico Mackenzie de Curitiba, PR. Resultados: Cerca de 58 indivíduos foram analisados; dentre eles 24 mulheres e 34 homens, com mediana da idade é de 57 anos. Dos pacientes acometidos pela psoriase, a hiperuricemia esteve presente em 13,7%, sendo mais prevalente no sexo masculino (p=0.01)., nos com artrite psoriásica (p=0.04) e naqueles com envolvimento ungueal (p=0.006) e mais rara naqueles com a forma vulgar da psoríase (p<0.0001). Nenhum paciente apresentou artrite gotosa. A atividade da doença de pele e da doença articular não interferiram nos níveis de ácido úrico (p=ns). Conclusão: Pacientes com artrite psoriásica têm maior incidência de hiperuricemia do que aqueles com psoríase só de pele. Hiperuricemia é mais comum nos pacientes masculinos, com envolvimento ungueal e menos comum naqueles com psoríase vulgar

Introduction: Psoriasis is a chronic, immunomodulated, genetic-based inflammatory disease with great polymorphism of clinical expression. It is characterized by the involvement of skin, nails and eventually joints. It has a worldwide occurrence, with prevalence between 2 and 3% in the general population. Between 20-30% of patients with psoriasis develop psoriatic arthritis (PA), which may precede, be associated with, or succeed psoriasis. Hyperuricemia is a condition often associated with psoriatic patients. Objectives: To study the prevalence of hyperuricemia in patients with psoriasis and its possible association with the phenotype of the disease, joint and skin activity. Methodology: This is a cross-sectional and analytical study conducted through the evaluation of uric acid in patients diagnosed with psoriasis (with and without PA) followed by dermatology and rheumatology outpatient clinics of the Mackenzie Evangelical University Hospital of Curitiba, PR. Results: About 58 individuals were analyzed; among them 24 women and 34 men, with a median age of 57 years. Of the patients affected by psoriasis, hyperuricemia was present in 13.7%, being more prevalent in males (p=0.01), in those with psoriatic arthritis (p=0.04) and in those with nail involvement (p=0.006) and less common in those with the vulgar form of psoriasis (p<0.0001). No patient had gouty arthritis. Skin disease and joint disease activities did not interfere with uric acid levels (p=ns). Conclusion: Patients with psoriatic arthritis have a higher incidence of hyperuricemia than those with skin-only psoriasis. Hyperuricemia is more common in male patients, with nail involvement and less common in those with psoriasis vulgaris

Effect of febuxostat on renal function in patients from South China with CKD3 diabetic nephropathy / Efeito do febuxostat na função renal em pacientes do sul da China com nefropatia diabética com DRC3

ABSTRACT Objective: To investigate the efficacy and safety of febuxostat on renal function in CKD stage 3 diabetic nephropathy patients. Methods: Patients in our hospital with chronic kidney disease (CKD) stage 3 diabetic nephropathy (DN) complicated by high serum uric acid (360 µmol/L) were recruited. Patients were then divided into treatment group and control group according to the random number table method. All the patients received low purine diet, renin-angiotensin-aldosterone system (RAAS) inhibitors, and adequate routine hypoglycemic treatment. Febuxostat was employed only in the treatment group. The levels of blood uric acid (sUA), serum creatinine (Scr), cystatin C (cys-c), eGFR, 24-hour urine protein quantification, albuminuria, and creatinine ratio (ACR) were evaluated in all patients before and after treatment at 4, 8, 12, and 24 week. Results: No difference was found before treatment between the two groups. After treatment at 4, 8, 12, and 24 week, the levels of sUA, SCr, cys-c, and eGFR between the two groups were significant different (P<0.05). There was no difference in 24-hour urine protein quantification, albuminuria, and creatinine ratio between two groups before treatment, and significant differences were observed after treatment. Fifty percent of patients from the treatment group achieved the treatment goal with 20 mg febuxostat at 4 weeks. Tubular markers were also decreased with the treatment. Conclusions: Febuxostat can reduce uric acid and improve renal function effectively in patients with CKD stage 3 diabetic nephropathy, while being well tolerated. However, the conclusion is still uncertain due to the short term of the study.

RESUMO Objetivo: Investigar a eficácia e segurança do febuxostat na função renal em pacientes com DRC estágio 3, com nefropatia diabética. Métodos: Foram recrutados pacientes em nosso hospital com nefropatia diabética (DN) estágio 3 de doença renal crônica (DRC) complicada por ácido úrico sérico alto (360 µmol/L). Os pacientes foram então divididos em grupo de tratamento e grupo controle, de acordo com o método da tabela de números aleatórios. Todos os pacientes receberam dieta pobre em purinas, inibidores do sistema renina-angiotensina-aldosterona (RAAS) e tratamento hipoglicêmico de rotina. O Febuxostat foi empregado apenas no grupo de tratamento. Os níveis de ácido úrico no sangue (AIU), creatinina sérica (Scr), cistatina C (cys-c), TFGe, quantificação de proteínas na urina em 24 horas, razão albumina e creatinina (ACR) foram avaliados em todos os pacientes antes e após o tratamento às 4, 8, 12 e 24 semanas. Resultados: Nenhuma diferença foi encontrada antes do tratamento entre os dois grupos. Após o tratamento nas 4, 8, 12 e 24 semanas, os níveis de sUA, SCr, cys-c e TFGe entre os dois grupos foram significativamente diferentes (P <0,05). Não houve diferença na quantificação de proteínas na urina em 24 horas, albuminúria e razão de creatinina entre dois grupos antes do tratamento, e diferenças significativas foram observadas após o tratamento. Cinquenta por cento dos pacientes do grupo de tratamento atingiram a meta de tratamento com 20 mg de febuxostat em 4 semanas. Marcadores tubulares também foram reduzidos com o tratamento. Conclusões: O Febuxostat pode reduzir o ácido úrico e melhorar a função renal efetivamente em pacientes com nefropatia diabética estágio com DRC no estágio 3, sendo bem tolerado. No entanto, a conclusão ainda é incerta devido ao curto prazo do estudo.

Recomendaciones para el manejo de la lisis tumoral / Recommendations for tumor lysis syndrome management

El síndrome de lisis tumoral representa una complicación potencialmente letal provocada por la liberación masiva de ácidos nucleicos, potasio y fosfato hacia la circulación como resultado de la lisis de células neoplásicas, las cuales se caracterizan por una rápida capacidad de proliferación y alta sensibilidad a fármacos. Esto puede ocurrir de forma espontánea antes del inicio del tratamiento y agravarse luego de haberse iniciado la quimioterapia. Presenta una alta mortalidad. Su prevención continúa siendo la medida terapéutica más importante. El cuadro clínico se caracteriza por la existencia de trastornos del metabolismo hidroelectrolítico, en particular, hipercalemia, hiperfosfatemia e hiperuricemia y por la aparición de una lesión renal aguda. Una adecuada intervención terapéutica implica hidratación intravenosa y medidas para prevenir o corregir las alteraciones metabólicas. En este artículo, se proponen lineamientos para seguir tanto en la etapa diagnóstica como en el tratamiento de esta complicación.

The tumor lysis syndrome represents a potentially lethal complication caused by the massive release of nucleic acids, potassium and phosphate into the circulation as a result of the lysis of neoplastic cells, which are characterized by a rapid proliferation capacity and high sensitivity to drugs. This may occur spontaneously prior to the start of treatment, becoming worse after the initiation of chemotherapy. It presents a high mortality; its prevention continues being the most important therapeutic measure. The clinical picture is characterized by the existence of hydroelectrolytic metabolism disorders, in particular hyperkalemia, hyperphosphatemia and hyperuricemia and by the appearance of an acute renal lesion. Adequate therapeutic intervention involves intravenous hydration and measures to prevent or correct metabolic alterations. This article proposes guidelines to follow both in the diagnostic stage and in the treatment of this complication.

Artritis Gotosa. 10 años de Seguimiento / Artritis Gotosa. 10 años de Seguimiento

Introduction: gouty arthritis is a persistent metabolic disease that produces an increase of the circulating uric acid, with the resulting deposit of monosodic urate crystals in the tissues. Objective: to characterize patients with gouty arthritis clinically and epidemiologically. Methods: a descriptive investigation of 72 patients with a diagnosis of gouty arthritis, assisted at Arnaldo Milián Castro Clinical Surgical University Hospital was carried out from January 2008 to December 2017. Results: patients between 40 and 49 years of age were the most representative group with a highest incidence in not white patients and the male sex. Obesity and hypertension prevailed as previous personal antecedents. Alcohol intake was the most represented toxic habit. A crisis of inflammation of the big toe was the more frequent starting manifestation. Swelling of soft tissues was the main radiologic alteration. Conclusion: gouty arthritis is present with a highest frequency in the male sex with a peak of incidence in the fourth decade of life. It is associated to bad diet habits and alcohol intake that could cause joint damage(AU)

Introducción: la artritis gotosa es una enfermedad metabólica persistente, que produce un aumento del ácido úrico circulante, con el consiguiente depósito de cristales de uratos monosódicos en los tejidos. Objetivo: caracterizar clínica y epidemiológicamente a los pacientes con artritis gotosa. Método: se realizó una investigación descriptiva de 72 pacientes con diagnóstico de artritis gotosa, atendidos en el Hospital Universitario Clínico Quirúrgico Arnaldo Milián Castro, entre enero del 2008 y diciembre del 2017. Resultados: los pacientes entre 40 y 49 años de edad fueron los más representativos, con mayor incidencia en no blancos y del sexo masculino. Predominó la obesidad y la hipertensión arterial como antecedentes patológicos personales. El alcohol fue el hábito tóxico mayoritariamente representado. La crisis de podagra resulto ser la manifestación inicial más usual. El aumento de partes blandas fue la principal alteración radiológica. Conclusiones: La gota se presenta con mayor frecuencia en el sexo masculino con un pico de incidencia en la cuarta década de la vida. Está asociada a malos hábitos dietéticos y al consumo de bebidas alcohólicas pudiendo ocasionar daño articular(AU)

Manejo de la Hiperuricemia en Pacientes en Argentina. Una Encuesta Mediante Cuestionario / Hyperuricemia Management in Patients from Argentina. A Questionnaire Survey

Resumen Introducción: Durante muchos años el ácido úrico se ha considerado como un producto metabólico inerte del metabolismo de las purinas, sin embargo, ha sido recientemente asociado a una serie de estados de enfermedad crónica. No hay hallazgos concluyentes disponibles en la actualidad para tomar una conducta activa clara respecto al tratamiento de ácido úrico sérico, y cuál sería su objetivo terapéutico. Material y métodos: Debido a esta controversia, se decidió llevar a cabo una encuesta para evaluar cuáles son las decisiones que se toman en este contexto, en el ámbito médico de la Argentina. Se consultó en qué pacientes se evaluaba en forma rutinaria el ácido úrico sérico, resultando en un 53.2% de todos los pacientes, sin diferenciar patologías, y un 11.5% refirió que no lo realiza rutinariamente. Con respecto al tratamiento sólo refirieron tratarlo con enfermedad renal un 62.5%; con diabetes 61.7%; con síndrome metabólico 60.4%; con enfermedad cardiovascular un 50.3%; con gota, cálculos renales o dolor articular, un 91.3%, 74% y 36.1% respectivamente. Resultados: Los datos de la encuesta confirman la falta de evidencia en el criterio para la selección de pacientes, a los fines de evaluar los niveles de ácido úrico sérico y su tratamiento. Conclusiones: De esta forma, se concluye que prima la necesidad de realizar estudios prospectivos y randomizados de las patologías con alta incidencia de uricemia elevada, para poder determinar normativas que orienten una conducta a los especialistas según los resultados obtenidos, y que dicha decisión no esté basada solo en la opinión de los expertos.

Abstract Introduction: For many years, uric acid was considered to be an inert product of purine metabolism; however, it has recently been associated with a number of chronic diseases. Nowadays, there are no conclusive findings available regarding a clear action plan to treat serum uric acid or which specific therapeutic goals it would have. Methods: Given this controversy, a survey was conducted in order to evaluate which decisions are taken regarding this situation within the Argentinian medical community. The question was in which cases serum uric acid was routinely assessed and the result was 53.2% no matter the pathology; 11,5% of physicians did not assess it routinely. Regarding its treatment, 62.5% of them reported to have treated it as part of kidney disease; 61.7 % as part of diabetes; 60.4% as part of metabolic syndrome; 50.3% as part of cardiovascular disease; 91.3 % as part of gout; 74% as part of renal stones, and 36.1% as part of joint pain. Results: The data collected by means of the survey show a lack of evidence for establishing the patient selection criteria when evaluating levels of serum uric acid and its treatment. Conclusions: Therefore, it is concluded that it is necessary to conduct prospective and randomized studies of conditions with a high incidence of elevated uricemia in order to develop guidelines for specialists according to results; this decision should not be based on experts' opinion alone.

Tres desafortunados enemigos de la salud de la población / Three unfortunate enemies of the health of the population

Resumen Tres enfermedades con alta prevalencia en la población adulta, especialmente en México, son la diabetes mellitus tipo 2, la hipertensión arterial y la hiperuricemia-gota; entre ellas comparten características fisiopatológicas que favorecen su aparición como Aceptado: 11 de junio 2019 un conjunto en los pacientes y cuyos tratamientos van frecuentemente de la mano, lo que ha permitido que en las siguientes líneas puedan describirse tales enfermedades Correspondencia como los tres desafortunados enemigos de la salud de la población. Manuel González Ortiz.

Abstract Three diseases with a high prevalence in the adult population, especially in Mexico, are type 2 diabetes mellitus, arterial hypertension and hyperuricemia-gout; they share among them pathophysiological characteristics that favor their appearance as a group in the patients and whose treatments are frequently in the same way, the above-mentioned has allowed that in the following lines can be described such diseases as the three to;35(4):596-608. unfortunate enemies of the health of the population.

Gota tofácea crónica en un adulto / Chronic tophaceous gout in an adult

Se presenta el caso clínico de un paciente de 57 años de edad, mestizo, con antecedentes de artritis reumatoidea y gota, quien acude a la consulta especializada de Dermatología del Hospital Clinicoquirúrgico Docente Celia Sánchez Manduley de Manzanillo, provincia de Granma, por presentar lesiones nodulares dolorosas diseminadas. Se realizaron estudios complementarios y biopsia de piel, cuyos resultados permitieron diagnosticar una gota tofácea crónica. El paciente llevaba tratamiento medicamentoso con prednisona, colchicina y metrotexate, pero luego de discutir el caso con los especialistas en medicina interna y reumatología se decidió sustituir la colchicina por el alopurinol.

The case report of a 57 year-old mestizo patient, is presented with a history of rheumatoid arthritis and gout who visited the specialized Dermatology department of Celia Sánchez Manduley Teaching Clinical-Surgical Hospital in Manzanillo, Granma province, for presenting disseminated painful nodular lesions. Complementary studies and skin biopsy were carried out which results allowed to diagnose a chronic . The patient was under drugs treatment with prednisona, colchicina and metrotexate, but after discussing the case with the specialists in internal medicine and rheumatology it was decided to sustitute colchicina by alopurinol.

Correlación entre concentraciones de ácido úrico y mortalidad hospitalaria en pacientes con evento vascular cerebral isquémico en un centro académico de alta especialidad / Correlation between uric acid levels and mortality in patients with ischemic cerebrovascular accident in an academic center

Resumen: ANTECEDENTES: El ácido úrico es un factor de riesgo independiente de enfermedades cardiovasculares y cerebrovasculares. OBJETIVO: Analizar el papel del ácido úrico como factor pronóstico en el accidente cerebrovascular isquémico. MATERIAL Y MÉTODO: Estudio de cohortes retrospectivo, efectuado en un hospital privado y académico. Se incluyeron pacientes con diagnóstico confirmado de evento vascular cerebral en el periodo de 2012 a 2016. Se clasificaron dos grupos: pacientes con hiperuricemia y sin hiperuricemia. RESULTADOS: Se analizaron 202 pacientes, 59 (30%) con hiperuricemia y 143 (70%) sin hiperuricemia. En el análisis comparativo la mortalidad fue de 7.3% (n = 10) en pacientes sin hiperuricemia y de 5% (n = 3) en pacientes con hiperuricemia (p = 0.56). Se encontraron diferencias significativas en las concentraciones de glucosa (p = 0.02), creatinina (p = 0.004), colesterol (p = 0.028), ácido úrico (p ≤ 0.0001) y triglicéridos (p = 0.014) entre ambas poblaciones. El análisis con regresión logística con corrección para potenciales de confusión no encontró asociación significativa entre la existencia de hiperuricemia al ingreso y la probabilidad de muerte (OR 2.098, IC95%: 0.47-9.332, p = 0.3304). CONCLUSIÓN: Este estudio demuestra que en los pacientes hospitalizados con diagnóstico de evento cerebrovascular isquémico las concentraciones de ácido úrico o la hiperuricemia no se relacionan con incremento en la mortalidad intrahospitalaria.

Abstract: BACKGROUND: Elevations in serum uric acid levels are considered a risk factor for cardiovascular and cerebrovascular conditions. OBJECTIVE: To analyze the relationship between high uric acid levels and the prognosis of patients with a cerebrovascular accident. MATERIAL AND METHOD: A retrospective cohort study performed at a single academic center. All patients with a confirmed diagnosis of cerebrovascular accident during the period between 2012 and 2016 were included in the analysis. Cohorts were segregated in patients with hyperuricemia and patients with normal serum uric acid levels. RESULTS: Two hundred two patients with cerebrovascular accident were analyzed, 59 patients (30%) were diagnosed with hyperuricemia, 143 (70%) were used as a control group. On a comparative analysis, mortality rates were 7.3% (n = 10) on hyperuricemia group vs 5% (n = 3) in the control group (p = 0.056). Significant differences were found on serum cholesterol levels (p = 0.028), uric acid (p ≤ 0.0001), glucose (p = 0.02), creatinine (p = 0.004) and triglycerides levels (p = 0.01) between cohorts. After controlling for potential confusing factors, there wasn't found an association between the increase in serum uric acid levels and the odds of mortality (OR 2.098, IC95% 0.47-9.332, p = 0.3304). CONCLUSIONS: This study demonstrates that inpatients diagnosed with a cerebrovascular accident mortality rates are not associated with hyperuricemia or increasing levels of serum uric acid.

Hidratación: importancia en algunas condiciones patológicas en adultos / Hydration: Importance in some pathological conditions in adults

Resumen Estar bien hidratado se relaciona con un estado adecuado de salud y bienestar; sin embargo ¿qué pasa en los pacientes adultos que tienen algún padecimiento como obesidad, diabetes mellitus tipo 2, hipertensión arterial, cardiopatía isquémica e insuficiencia cardiaca, alteraciones nefrológicas (insuficiencia, poliquistosis y litiasis renal), enfermedad pulmonar obstructiva crónica, dislipidemia, hiperuricemia o, bien, en adultos mayores y en el periodo perioperatorio, en donde hay pérdida del estado de salud o una necesidad diferente de hidratación y que requieren consumir bebidas no alcohólicas para tener un buen estado de hidratación sin alterar la evolución natural de estas condiciones? Algunos puntos y recomendaciones son: la carbonatación de las bebidas ofrece el beneficio de aumentar la saciedad y disminuir la ingesta energética, lo que puede contribuir a la pérdida de peso; el agua simple es la mejor fuente de hidratación en los pacientes diabéticos, sin embargo, otras fuentes de hidratación pueden ser el agua mineralizada, el agua mineral, la leche (de preferencia descremada), café y té sin azúcar o con edulcorantes no calóricos o bajos en calorías, así como cualquier bebida que los contenga; en pacientes con litiasis renal se recomienda ingerir 2.5 a 4 L de agua al día; las bebidas para deportistas pueden ser consumidas por pacientes hipertensos, siempre y cuando no excedan la cantidad de sodio recomendada por la Organización Mundial de la Salud. En conclusión, la hidratación juega un papel importante en la evolución de las enfermedades mencionadas.

Abstract Being well hydrated is related to an adequate state of health and well-being; however, what happens in those adult patients having some pathological conditions such as obesity, type 2 diabetes mellitus, high blood pressure, ischemic heart disease and heart failure, kidney diseases (renal failure, polycystic renal disease and renal lithiasis), chronic obstructive pulmonary disease, dyslipidemia, hyperuricemia, or in the elderly and in the perioperative period, where there is loss of health or a different need for hydration and require the use of non-alcoholic beverages in order to have a good state of hydration without altering the natural evolution of these conditions? Some key points and recommendations are: carbonation of beverages offers the benefit of increasing satiety and decreasing energy intake, which can contribute to weight loss; simple water is the best source of hydration in diabetic patients; however, other sources of hydration may be mineralized water, mineral water, milk (preferably non-fat), coffee and tea without sugar or non-caloric sweeteners or low-calorie, as well as any beverage containing them; in patients with renal lithiasis it is recommended to take 2.5 to 4 L of water per day; sports drinks can be consumed by hypertensive patients as long as they do not exceed the amount of sodium recommended by the World Health Organization. In conclusion, hydration plays an important role in the evolution of the pathologic conditions mentioned above.

Hiperuricemia e hipertensión arterial sistémica: ¿cuál es la relación? / Hyperuricemia and systemic arterial hypertension: what is the relationship?

Resumen El ácido úrico es producto final del metabolismo de las purinas, transformadas finalmente a ácido úrico. No existe definición universal de hiperuricemia, en la práctica, el punto de corte es a partir de 6.8 mg/dL en plasma. Estudios experimentales han demostrado una correlación positiva lineal entre la presión arterial y las concentraciones de ácido úrico, así como disminución de las cifras tensionales al administrar tratamiento hipouricemiante con alopurinol. Se han identificado numerosos mecanismos a través de los cuales la hiperuricemia puede causar hipertensión: reducción de las concentraciones de óxido nítrico endotelial, estimulación de estrés oxidativo, expresión en las células de músculo liso del endotelio vascular de receptor URAT-1, activación del eje renina angiotensina, estimulación de la proliferación de músculo liso vascular, además, favorece la enfermedad microvascular renal. La evidencia reciente ha aportado nuevo conocimiento acerca de los múltiples mecanismos a través de los cuales el ácido úrico tendría un papel preponderante en la hipertensión arterial sistémica y en múltiples alteraciones metabólicas; sin embargo, hace falta desarrollar estudios clínicos a gran escala, bien diseñados, que comprueben de manera más contundente estas teorías, antes de considerar tratamientos enfocados en el manejo de la hiperuricemia asintomática en la práctica clínica diaria.

Abstract Uric acid is the end product of purine metabolism, ultimately converted to uric acid. There is no universal definition of hyperuricemia, in practice, the cutoff point is from 6.8mg/dL in plasma. The relationship between hyperuricemia and hypertension has been demonstrated in many experimental studies. Experimental studies have shown a linear positive correlation between blood pressure and uric acid levels, as well as a decrease in blood pressure figures with therapy with allopurinol. Numerous mechanisms have been identified through which hyperuricemia can cause hypertension: reduction of endothelial nitric oxide levels, stimulation of oxidative stress, expression in smooth muscle cells of the vascular endothelium of URAT-1 receptor, activation of the renin-angiotensin axis, stimulation of vascular smooth muscle proliferation also favors the development of renal microvascular disease. Recent evidence has provided new insight into the multiple mechanisms through which UA would play a major role both in systemic arterial hypertension and in multiple metabolic alterations; however, large-scale, well-designed clinical studies are needed, which prove more conclusively these theories, before considering therapies focused on the management of asymptomatic hyperuricemia in daily clinical practice