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.

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.

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.

Effects of hyperuricemia on incident renal replacement therapy and all-cause mortality among patients with chronic kidney disease stages 3-5: a retrospective cohort study

ABSTRACT BACKGROUND: Findings regarding the effects of hyperuricemia on renal function and mortality have been inconsistent. OBJECTIVES: To investigate the effects of hyperuricemia on incident renal replacement therapy and all-cause mortality among patients with chronic kidney disease (CKD). DESIGN AND SETTING: Retrospective cohort study conducted in a medical center in Taiwan. METHODS: Patients with CKD in stages 3-5, without histories of renal replacement therapy, were consecutively recruited from 2007 to 2013. Their medical history, laboratory and medication data were collected from hospital records. The mean uric acid level in the first year of follow-up was used for analyses. Hyperuricemia was defined as mean uric acid level ≥ 7.0 mg/dl in men or ≥ 6.0 mg/dl in women. The primary outcomes were incident renal replacement therapy and all-cause mortality, and these data were retrospectively collected from hospital records until the end of 2015. RESULTS: A total of 4,381 patients were analyzed (mean age 71.0 ± 14.8 years; males 62.7%), and the median follow-up period was 2.5 years. Patients with hyperuricemia were at increased risk of incident renal replacement therapy and all-cause mortality, especially those with CKD in stages 4 or 5. Compared with patients with CKD in stage 3 and normouricemia, patients with CKD in stages 4 or 5 presented significantly higher risk of all-cause mortality only if they had hyperuricemia. CONCLUSIONS: In patients with CKD in stages 3-5, hyperuricemia was associated with higher risk of incident renal replacement therapy and all-cause mortality. Whether treatment with uric acid-lowering drugs in these patients would improve their outcomes merits further investigation.

The specific impact of uremic toxins upon cognitive domains: a review / O impacto específico de toxinas urêmicas em domínios cognitivos: uma revisão

ABSTRACT One of the mechanisms proposed for chronic kidney disease (CKD)-related cognitive impairment is the accumulation of uremic toxins due to the deterioration of the renal clearance function. Cognition can be categorized into five major domains according to its information processing functions: memory, attention, language, visual-spatial, and executive. We performed a review using the terms 'uric acid', 'indoxyl sulfate', 'p-cresyl sulfate', 'homocysteine', 'interleukins' and 'parathyroid hormone'. These are the compounds that were found to be strongly associated with cognitive impairment in CKD in the literature. The 26 selected articles point towards an association between higher levels of uric acid, homocysteine, and interleukin 6 with lower cognitive performance in executive, attentional, and memory domains. We also reviewed the hemodialysis effects on cognition. Hemodialysis seems to contribute to an amelioration of CKD-related encephalopathic dysfunction, although this improvement occurs more in some cognitive domains than in others.

RESUMO Um dos mecanismos propostos para explicar o comprometimento cognitivo relacionado à doença renal crônica (DRC) é o acúmulo de toxinas urêmicas devido à deterioração da função de depuração renal. A cognição pode ser categorizada em cinco domínios principais de acordo com suas funções de processamento de informações: memória, atenção, linguagem, visual-espacial e executiva. Realizamos uma revisão usando os termos "ácido úrico", "indoxil sulfato", "p-cresil sulfato", "homocisteína", "interleucinas" e "paratormônio". Estes são os compostos que se mostraram fortemente associados ao comprometimento cognitivo na DRC na literatura. Os 26 artigos selecionados apontam para uma associação entre níveis mais elevados de ácido úrico, homocisteína e interleucina-6 com menor desempenho cognitivo nos domínios executivo, atenção e de memória. Também revisamos os efeitos da hemodiálise na cognição. A hemodiálise parece contribuir para uma melhoria da disfunção encefalopática relacionada à DRC, embora essa melhora ocorra mais em alguns domínios cognitivos do que em outros.

Abdominal obesity and reduction of glomerular filtration

SUMMARY The objective was to evaluate the association between nutritional status and the glomerular filtration rate (GFR) in remaining quilombolas. Cross-sectional study carried out on 32 remaining quilombola communities in the municipality of Alcântara-MA. The nutritional indicators (IN) used were: body mass index (BMI); Waist circumference (WC); Waist-to-hip ratio (WHR); Waist-to-height ratio (WHtR); conicity index (CI) and estimated visceral adipose tissue (VAT). GFR was estimated from the CKD-EPI creatinine-cystatin C formula. The Shapiro Wilk test was used to evaluate the normality of the quantitative variables. In order to compare the second IN sex, the chi-square test was applied. The Anova or Kruskal-Wallis tests were used to verify the association between IN and GFR. Of the 1,526 remaining quilombolas studied, 89.5% were black or brown, 51.2% were women, 88.6% belonged to economic classes D and E and 61.2% were farmers or fishermen. Clinical investigation revealed 29.2% of hypertensive patients, 8.5% of diabetics and 3.1% with reduced GFR. The BMI revealed 45.6% of the remaining quilombolas with excess weight. When compared to men, women presented a higher prevalence of overweight by BMI (56.6% vs 33.8%, p <0.001) and abdominal obesity CC (52.3% vs 4.3%), WHR (76,5% vs 5.8%), WHtR (82.3% vs 48.9%) and VAT (27.1% vs 14.5%) (p <0.001). Comparing the means of IN according to the GFR, it was observed that the higher the mean value of the IN lower the GFR (p <0.05). The GFR reduced with increasing mean values of nutritional indicators of abdominal obesity, regardless of sex.

RESUMO O objetivo foi avaliar a associação entre o estado nutricional e a taxa de filtração glomerular (TFG) em remanescentes quilombolas. Estudo transversal, realizado em 32 comunidades remanescentes de quilombolas, no município de Alcântara - MA. Os indicadores nutricionais (IN) utilizados foram: índice de massa corporal (IMC); circunferência da cintura (CC); relação cintura-quadril (RCQ); relação cintura-estatura (RCEst); índice de conicidade (Índice C) e tecido adiposo visceral estimado (TAVe). A TFG foi estimada a partir da fórmula do CKD-EPI creatinina-cistatina C. O teste Shapiro Wilk foi utilizado para avaliar a normalidade das variáveis quantitativas. Para comparar os IN segundo sexo foi aplicado o teste qui-quadrado. Os testes Anova ou Kruskal-Wallis foram usados para verificar a associação entre os IN e a TFG. Dos 1.526 remanescentes quilombolas estudados, 89,5% eram da cor preta ou parda, 51,2% eram mulheres, 88,6% pertenciam às classes econômicas D e E e 61,2% eram lavradores ou pescadores. A investigação clínica revelou 29,2% de hipertensos, 8,5% de diabéticos e 3,1% com TFG reduzida. O IMC revelou 45,6% dos remanescentes quilombolas com excesso de peso. Quando comparadas aos homens, as mulheres apresentaram maior prevalência de excesso de peso pelo IMC (56,6% vs. 33,8%; p <0,001) e obesidade abdominal CC (52,3% vs. 4,3%), RCQ (76,5% vs. 5,8%), RCEst (82,3% vs. 48,9%) e TAVe (27,1% vs. 14,5%) (p<0,001). Comparando as médias dos IN segundo a TFG observou-se que, quanto maior o valor médio dos IN, menor a TFG (p<0,05). A TFG foi reduzida com o aumento dos valores médios dos indicadores nutricionais de obesidade abdominal, independentemente do sexo.

Levels of uric acid and increased diastolic blood pressure: Risk factors for atrial fibrillation in patients older than 60 years / Niveles de ácido úrico y presión arterial diastólica elevada: factores de riesgo de fibrilación atrial en pacientes mayores de 60 años

Summary Objective: To characterize the maximum P-wave duration (Pmax) and P-wave dispersion (PWD) according to blood pressure (BP) and uric acid (UA) levels in geriatric patients. Method: An analytical study was performed in 83 patients aged over 60 years treated at the Family Medical Office 5 of the Aracelio Rodríguez Castellón Polyclinic, in Cienfuegos, Cuba between January and December 2015. The sample was divided into two groups (patients with hyperuricemia and patients with normal UA levels). Results: We found a linear and significant correlation between diastolic BP and Pmax in patients with hyperuricemia (r=0.695; p=0.026), but not in patients with normal UA (r=0.048; p=0.757). A linear and significant correlation was demonstrated between diastolic BP and PWD in patients with hyperuricemia (r=0.657; p=0.039), but not in patients with normal UA (r=0.054; p=0.730). Conclusion: There is correlation between diastolic BP and Pmax plus PWD in elderly patients with hyperuricemia.

Resumen Objetivo: Caracterizar la máxima duración de la onda P (Pmáx) y la dispersión de la onda P (DP) según las cifras de tensión arterial (TA) y los niveles de ácido úrico en pacientes geriátricos. Método: Se realizó un estudio analítico en 83 pacientes mayores de 60 años pertenecientes al Consultorio Médico de la Familia 5 del Policlínico Aracelio Rodríguez Castellón, Cienfuegos, Cuba entre enero y diciembre de 2015. La muestra se dividió en dos grupos (pacientes con hiperuricemia y pacientes con AU normal). Resultados: Existe correlación lineal y significativa entre la tensión arterial diastólica y la Pmáx en los pacientes con hiperuricemia (r=0,695; p=0,026), mas no en los pacientes con AU normal (r=0,048; p=0,757). Se demuestra correlación lineal y significativa entre la tensión diastólica y la DP en los pacientes con hiperuricemia (r=0,657; p=0,039), aunque no en los pacientes con AU normal (r=0,054; p=0,730), respectivamente. Conclusión: Existe correlación entre la Pmáx y la DP y las cifras de tensión arterial diastólica en pacientes geriátricos con hiperuricemia.

Gordura Corporal e Ácido Úrico Estão Relacionados com Escores de Risco Cardiovascular? Análise Transversal no Programa de Intervenção PROCADIO-UFV / Are Body Fat and Uric Acid Associated with Cardiovascular Risk Scores? Cross-Sectional Analysis in the PROCARDIO-UFV Trial

Fundamentos: Os escores de risco são ferramentas utilizadas para indicar a probabilidade de ocorrência de certo evento cardiovascular e identificar previamente os indivíduos com baixo, médio e alto risco para desenvolvimento de doenças cardiovasculares. Objetivo: Estabelecer o risco cardiovascular dos usuários de um programa de atenção à saúde cardiovascular de uma universidade, bem como avaliar a relação dos mesmos com estilo de vida, dados clínicos, sociodemográficos e outros marcadores de risco cardiometabólico. Métodos: Estudo transversal com amostra de 197 participantes, dos quais foram coletados dados demográficos, antropométricos, clínico-metabólicos, hábitos alimentares e do estilo de vida por meio do Escore de Risco Global e do Escore de Risco de Framingham. Valor de p < 0,05 foi considerado estatisticamente significante. Resultados: De acordo com o Escore de Risco de Framingham, 84% da população analisada foi considerada baixo risco e 16% de risco intermediário/alto, enquanto que, de acordo com Escore de Risco Global, 18% foram baixo risco, 45% de risco intermediário e 37% de alto risco para infarto ou morte por doença coronária em 10 anos. Conclusão: O excesso de peso corporal e os valores séricos de ácido úrico se demonstraram importantes marcadores de risco cardiovascular, além daqueles dos escores, de modo que deveriam ser considerados na prática clínica

Background: Risk scores are tools used to indicate the probability of occurrence of a certain cardiovascular event and to previously identify individuals at low, medium, and high risk for the development of cardiovascular diseases. Objective: To establish the cardiovascular risk of users of a cardiovascular health attention program of a university, and assess its association with lifestyle, clinical, sociodemographic data, and other cardiometabolic risk markers. Methods: Cross-sectional study with a sample of 197 participants. Demographic, anthropometric, clinical, and metabolic data, eating habits and lifestyle information were collected using the Global Risk Score and the Framingham Risk Score. P-value < 0,05 was considered statistically significant. Results: According to the Framingham Risk Score, 84% of the assessed population was considered low risk and 16% as intermediate/high risk. However, according to the Global Risk Score, 18% of the participants were low risk, 45% were intermediate risk and 37% were high risk for infarction or death from coronary heart disease in 10 years. Conclusion: Excess body weight and uric acid serum levels showed to be significant cardiovascular risk markers in addition to those of the score and, consequently, they should be considered in clinical practice

Insulin resistance and associated factors: a cross-sectional study of bank employees

OBJECTIVE: Insulin resistance is characterized by the failure of target cells to respond to normal levels of circulating insulin, and this condition is related to cardiovascular disease. This study sought to evaluate the prevalence of insulin resistance and its association with markers of metabolic abnormalities and metabolic syndrome in bank employees. METHODS: A cross-sectional study was performed on 498 working men and women aged ≥20 years old. The Homeostasis Model Assessment (HOMA-IR) was used to determine the presence of insulin resistance based on cut-off values of ≤2.71 for normal insulin levels and >2.71 for insulin resistance, as established for the adult Brazilian population. RESULTS: It was observed that the 52 (10.4%) overweight individuals with insulin resistance were 4.97 times (95%CI 1.31-18.83) more likely to have high HOMA-IR values than the normal-weight participants; among those who were obese, the likelihood increased to 17.87 (95%CI 4.36-73.21). Individuals with large waist circumferences were 3.27 times (95%CI 1.03-10.38) more likely to develop insulin resistance than those who were within normal parameters. The HOMA-IR values differed between subjects with and without metabolic syndrome, with values of 2.83±2.5 and 1.10±0.81 (p=0.001), respectively. The levels of insulin, ultrasensitive C-reactive protein and uric acid were also associated with insulin resistance. CONCLUSION: The prevalence of insulin resistance among bank employees is high, and insulin resistance is associated with and serves as a marker of metabolic syndrome. Cardiovascular disease and metabolic syndrome-associated metabolic abnormalities were observed, and insulin resistance may be a risk factor in this group of professionals.

Relationship between uric acid levels and risk of chronic kidney disease in a retrospective cohort of Brazilian workers

Uric acid (UA) levels are increased in patients with kidney dysfunction. We analyzed the association between asymptomatic hyperuricemia and new-onset chronic kidney disease (CKD). A retrospective cohort study was designed to collect data from employees of an energy generation and distribution company in the city of Rio de Janeiro, Brazil, who had undergone the company's annual medical checkup from 2008 to 2014. People with ≤2 years of follow-up, with baseline estimated glomerular filtration rate (eGFR) <60 mL·min-1·(1.73 m2)-1 or with incomplete data were excluded. The endpoint was defined as eGFR <60 mL·min-1·(1.73 m2)-1 estimated through the chronic kidney disease epidemiology collaboration equation (CKD-EPI). The study included 1094 participants. The mean follow-up period was 5.05±1.05 years and 44 participants exhibited new-onset CKD. The prevalence of hyperuricemia was 4.2%. There was a significant inverse correlation between baseline serum levels of UA and baseline eGFR (R=-0.21, P<0.001). Female gender (OR=4.00; 95%CI=1.92-8.29, P<0.001) and age (OR=1.06; 95%CI=1.02-1.11, P=0.004) but not UA levels (OR=1.12; 95%CI=0.83-1.50; P=0.465) were associated with new-onset CKD. Diabetes mellitus and body mass index were independent factors for fast progression (OR=2.17; 95%CI=1.24-3.80, P=0.007 and OR=1.04; 95%CI=1.01-1.07; P=0.020). These results did not support UA as an independent predictor for CKD progression in the studied population.

Factores de riesgo cardiovascular lipídicos y no lipídicos en una población adulta / Lipid and non-lipid cardiovascular risk factors in an adult population / Fatores de risco cardiovascular lipídicos e não-lipídicos em uma população adulta

Las enfermedades cardiovasculares (EC) constituyen la principal causa de muerte de la población adulta, por lo que es importante conocer y controlar los factores de riesgo. El propósito del estudio fue evaluar el nivel de riesgo cardiovascular asociado a lípidos séricos y otros factores de riesgo no lipídicos, en una población adulta. Se realizó un estudio descriptivo y transversal en 95 adultos de 23-51 años (44 mujeres, 51 hombres). Se determinaron la glucosa, el perfil lipídico, el ácido úrico y la proteína C reactiva en suero. Se midió la presión arterial, el peso, la talla y se calculó el índice de masa corporal. Se obtuvieron datos sobre antecedentes familiares de EC, diabetes o hipertensión, hábitos de tabaco y alcohol y actividad física. Los resultados mostraron que los adultos del sexo masculino y aquellos con más de 30 años de edad presentaron mayor frecuencia de factores de riesgo lipídicos, así como una mayor prevalencia de alteraciones para los índices de riesgo cardiometabólico, respecto al sexo femenino y a los menores de 30 años. Igualmente, los hombres mostraron mayor prevalencia de algunos factores de riesgo no lipídicos (ácido úrico elevado, sobrepeso, presión arterial elevada). Aunque se encontró una baja prevalencia en cuanto a la acumulación de factores de riesgo lipídicos, una proporción importante de la muestra presentó 3 o más factores de riesgo no lipídicos. Adicionalmente, más del 70% de los adultos evaluados, presentó 3 o más factores de riesgo lipídicos o no lipídicos. Estos hallazgos sugieren la necesidad de implementar modelos de promoción de salud y prevención de la enfermedad que integren el conocimiento, la detección y el manejo de los factores de riesgo con base en la modificación de estilos de vida.

Cardiovascular disease (CVD) is the leading cause of death in the adult population, so it is important to know and control the risk factors. The purpose of the study was to assess the level of cardiovascular risk associated with serum lipids and other non-lipid risk factors in an adult population. A descriptive study was made on 95 adults of 23-51 years of age (44 women, 51 men). Glucose, lipid profile, uric acid and C-reactive protein in serum were determined. Blood pressure, weight and height were measured and body mass index was calculated. Data on family history of CVD, diabetes or hypertension, smoking and alcohol habits and physical activity were obtained. The results showed that male adults and those over 30 years of age had a higher frequency of lipid risk factors, as well as a higher prevalence of alterations to cardio metabolic risk indices, compared to women and adults less than 30 years old. Men also showed greater prevalence of some non-lipid risk factors (high uric acid, obesity and high blood pressure). Although a low prevalence was found in terms of the accumulation of lipid risk factors, a significant proportion of the sample presented 3 or more non-lipid risk factors. Additionally, over 70% of adults evaluated showed 3 or more lipid or non-lipid risk factors These findings suggest the need to implement models of health promotion and disease prevention, integrating knowledge, detection and management of risk factors based on lifestyle changes.

As doenças cardiovasculares (DCV) são a principal causa de morte da população adulta, por isso é importante conhecer e controlar os fatores de risco. O objetivo do estudo foi avaliar o nível de risco cardiovascular associado a lipídios séricos e outros fatores de risco não-lipídicos em uma população adulta. Realizou-se um estudo descritivo e transversal em 95 adultos de 23-51 anos (44 mulheres, 51 homens). Foram determinados glicose, perfil lipídico, ácido úrico e proteína C-reativa em soro. Foi medida a pressão arterial, peso, altura e se calculou o índice de massa corporal. Obtiveram-se dados sobre história familiar de doenças cardiovasculares, diabetes ou hipertensão, hábitos de álcool e tabagismo e atividade física. Os resultados mostraram que os homens adultos e as pessoas com mais de 30 anos de idade apresentaram maior frequência de fatores de risco lipídicos, bem como uma maior prevalência de alterações para os índices de risco cardiometabólico, em comparação com as mulheres e os menores de 30 anos. Os homens também apresentaram maior prevalência de alguns fatores de risco não lipídicos (ácido úrico elevado, obesidade, pressão arterial elevada). Embora tenha sido encontrada baixa prevalência em termos de acumulação de fatores de risco de lipídios, uma proporção significativa da amostra apresentou três ou mais fatores de risco não-lipídicos. Além disso, mais de 70% dos adultos avaliados mostrou 3 ou mais fatores de risco lipídico ou não-lipídico. Estes achados sugerem a necessidade da implementação de modelos de promoção da saúde e prevenção de doenças, integrando o conhecimento, detecção e gestão dos fatores de risco com base na mudança de estilos de vida.

Serum uric acid and its association with hypertension, early nephropathy and chronic kidney disease in type 2 diabetic patients / Ácido úrico sérico e sua associação com hipertensão, nefropatia precoce e doença renal crônica em pacientes diabéticos tipo 2

Abstract Introduction: Early detection diabetic nephropathy (DN) is important. Whether serum uric acid (SUA) has a role in the development of DN is not known. Objective: To study the relationship between SUA and hypertension, early nephropathy and progression of chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM). Methods: The total number of the study was 986 participants, according to presence and duration of diabetes were classified into three groups. Group I; including 250 healthy participants. Group II; including 352 with onset of diabetes < 5 years. Group III; including 384, with the onset of diabetes > 5 years. All participants were submitted to complete clinical examination, anthropometric measurements, laboratory investigations, including glycosylated hemoglobin (HbA1C), as well triglycerides to high-density lipoprotein ratios (TG/HDL-C), SUA, urinary albumin/creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). Results: SUA, BP, HbA1c, TG/HDL-C ratio, and ACR levels were significantly higher in group III than group I, II and in II than I. eGFR significantly lower in group III than group I, II and in II than I (p < 0.001). Age, BMI, BP, HbA1c, TG/HDL-C, ACR, were positively correlated with SUA, while GFR negatively correlated. SUA at level of > 6.1 mg/dl, > 6.2 mg/dl and > 6.5 mg/dl had a greater sensitivity and specificity for identifying hypertension, early nephropathy and decline eGFR respectively. Conclusion: Even high normal SUA level, was associated with the risk of hypertension, early nephropathy and decline of eGFR. Moreover SUA level may identify the onset of hypertension, early nephropathy and progression of CKD in T2DM.

Resumo Introdução: A detecção precoce da nefropatia diabética (ND) é importante. O ácido úrico sérico (AUS) tem um papel ainda desconhecido no desenvolvimento de ND. Objetivo: Estudar a relação entre AUS e hipertensão, nefropatia precoce e progressão da doença renal crônica (DRC) no diabetes mellitus tipo 2 (DM2). Métodos: O estudo contou com 986 participantes, de acordo com a presença e a duração do diabetes, os pacientes foram classificados em três grupos. O Grupo I incluiu 250 participantes saudáveis. O Grupo II incluiu 352 pacientes com início de diabetes < 5 anos. O Grupo III incluiu 384 pacientes com o aparecimento de diabetes > 5 anos. Todos os participantes foram submetidos a exame clínico completo, medidas antropométricas, exames laboratoriais - incluindo hemoglobina glicosilada (HbA1C), bem como a razão entre triglicérides e lipoproteína de alta densidade (TG/HDL-C), AUS, razão creatinina/albumina (RCA) urinária, e taxa estimada de filtração glomerular (eTFG). Resultados: A razão AUS, PA, HbA1c, TG/HDL-C e RCA foi significativamente maior no grupo III do que no grupo I, II e em II do que I. A eTFG foi significativamente menor no grupo III do que nos grupos I, II e no II do que no I (p < 0,001). Idade, IMC, PA, HbA1c, razão TG/HDL-C, RCA, foram positivamente correlacionados com AUS, enquanto que a TFG esteve negativamente correlacionada. O AUS a níveis > 6,1 mg/dl, > 6,2 mg/dl e > 6,5 mg/dl apresentou maior sensibilidade e especificidade para identificar hipertensão, nefropatia precoce e declínio da eTFG, respectivamente. Conclusão: Mesmo elevados níveis de AUS, foi associado ao risco de hipertensão, nefropatia precoce e declínio da eTFG. Além disso, o nível de AUS pode identificar o início da hipertensão, nefropatia precoce e progressão da DRC em DM2.

Are patients with lichen planus really prone to urolithiasis? Lichen planus and urolithiasis

ABSTRACT Purpose to investigate whether patients with lichen planus (LP) are really prone to urolithiasis or not. Patients and Methods We performed a prospective analysis of 40 patients diagnosed with lichen planus (LP) (group I), and 40 volunteers did not have LP before (group II). Participants were all checked for urolithiasis by radiological investigations. Blood samples were analyzed for biochemistry parameters including calcium and uric acid. 24-h urine samples were analyzed to investigate oxalate, citrate calcium, uric acid, magnesium, sodium and creatinine. Results Men/women ratio and mean age were similar between group I and II (p>0.05). A presence or history of urolithiasis was detected in 8 (20%) and 2 (%5) patients in group I and II, respectively (p<0.05). Hypocitraturia was the most common anomaly with 35% (n:14) in group I. The rate of hypocitraturia in group II was 12.5% (n:5) and the difference was statistically significantly different (p=0.036). In group I, hyperuricosuria and hyperoxaluria followed with rates of 27.5% (n:11) and 25% (n:10), respectively. The rate of hyperuricosuria and hyperoxaluria were both 5% (n:2) in group II and the differences were significant (p<0.05). Hyperuricemia was another important finding in the patients with LP. It was detected in 13 (32.5%) patients in group I and in 1 (2.5%) participant in group II (p=0.001). Conclusion According to our results, metabolic disorders of urolithiasis were highly detected in the patients with LP. However, similar to the etiology of LP, the exact reasons for these metabolic abnormalities in LP remain a mystery.

Hiperuricemia, enfermedad renal crónica y trasplante renal (parte I) / Hyperuricemia, chronic kidney disease and kidney transplant (part I)

La hiperuricemia post trasplante ha sido definida con valores iguales a la población general, en su prevalencia pueden alcanzar un 80% en los que han recibido un trasplante renal, un 5-25% desarrolla crisis gotosas. La edad avanzada al momento del implante, la historia de hiperuricemia o gota, la obesidad, el tratamiento con anticalcineurínicos, el uso de diuréticos y el bajo filtrado glomerular son algunos de los factores implicados en su desarrollo. La hiperuricemia se han relacionado con disminución de la vasodilatación mediada por óxido nítrico y la proliferación del músculo liso vascular a través de efectos proinflamatorios y profibróticos (mediados por células T, macrófagos, PDGF, TGF ß, entre otros). Estos efectos se han asociado a su vez con hipertensión arterial, afecciones cardiovasculares y progresión del daño renal (relacionado con fibrosis túbulo intersticial, arterioloesclerosis de la aferente, atrofia tubular), factores que conllevan a una reducción en la sobrevida del injerto como del paciente. La indicación de tratamiento de la hiperuricemia asintomática en esta población es aún objeto de debate, tanto respecto de la indicación en sí como del tipo de fármaco a utilizar, a diferencia de lo que ocurre en litiasis, tofos o artritis donde se debe encarar el tratamiento, jerarquizando la interacción con las drogas propias del trasplante. Se debe considerar que la mayoría de la información disponible se desprende del análisis sobre población general por lo que se requieren estudios de este grupo poblacional en particular.

Post-transplant hyperuricemia has been defined with equal values to the ones of general population, its prevalence can reach 80% in those who have received a kidney transplant, and 5 to 25% can develop gout crisis. Advanced age at implant, history of hyperuricemia or gout, obesity, treatment with calcineurin inhibitors, use of diuretics and low glomerular filtration rate are some of the factors involved in its development. Hyperuricemia has been linked to decreased nitric oxide mediated vasodilation and proliferation of vascular smooth muscle through proinflammatory and profibrotic effects (mediated by T cells, macrophages, PDGF, TGF ß among others). These effects have been associated, in turn, with hypertension, cardiovascular disease and renal damage progression (related tubulointerstitial fibrosis, arteriosclerosis of afferent tubular atrophy) factors that lead to a reduction in graft and patient survival. Indication for asymptomatic hyperuricemia treatment in this population is still under debate, both in terms of the indication in itself and the type of drug used, unlike what happens in stones, arthritis, or tophi where they must face treatment must be addressed, prioritizing the interaction with the drugs used in transplantation. It must be considered that most of the available information comes from the analysis of general population, therefore studies on this population group are particularly required

Marcadores de estrés oxidativo y su relación con el estado nutricional en adultos, Ecuador / Relationships between biomarkers of oxidative stress and nutritional status in adults, Ecuador

Se evaluó la relación entre biomarcadores de estrés oxidativo (ácido úrico, bilirrubina y proteína C-reactiva) con el estado nutricional en 321 adultos de Ecuador, pertenecientes al personal administrativo de la Universidad Técnica del Norte, con edades de 43 ± 10 años, (46,30% femenino y 53,61% masculino). Se obtuvo información sociodemográfica, de estilo de vida y epidemiológica; se calculó el índice de Masa Corporal (IMC), porcentaje de grasa y agua corporal, se midió la circunferencia de la cintura (CC) y la presión arterial y se determinó las concentraciones de ácido úrico, bilirrubina y Proteína C reactiva (PCR). Se encontró que 17,9% de la población presentó obesidad y 51,72% sobrepeso. Los valores más elevados de ácido úrico se encontraron en obesos, hipertensos y en quienes realizan actividad física. La bilirrubina total, directa e indirecta se encontró en límites superiores en los grupos con obesidad abdominal, y con actividad física. Las variables % de grasa y de agua influyen en la PCR en el grupo con baja grasa corporal y en las mujeres. En hombres, la PCR se asocia con IMC y CC. En los grupos sobrepeso, alta grasa corporal y PHT, el ácido úrico mostró relación con el % de grasa y la CC En los obesos con el % de agua e IMC y en los grupos obesidad abdominal e HT se asoció con % de agua y CC Se concluye que el porcentaje de agua corporal es un importante indicador nutricional para el desarrollo de estrés oxidativo en esta población.

In this work it was evaluated the relationship between oxidative stress biomarkers (uric acid, bilirubin and C-reactive protein) with nutritional status in 321 adults of Ecuador, belonging to administrative staff of of the Universidad Tècnica del Norte , aged 43 ± 10 years old (46 30% female and 53.61% male). Socio demographic and epidemiological information and lifestyle were obtained through a survey; The Body Mass Index (BMI) and body fat and body water percentages were calculated; waist circumference (WC) and blood pressure was measured. Determinations of uric acid, bilirubin, and serum C-reactive protein (PCR) were performed. 17.9% of the populations were obese and 51.72% overweight. The highest values of uric acid were found in obese, hypertensive and physical activity groups. The total direct and indirect bilirubin were found in upper limits in abdominal obesity and physical activity groups. The CRP level was influenced by % fat and % water in the low body fat group and in females. In male, BMI and WC were associated with CRP. Uric acid showed relationship with % fat and WC in overweight, high body fat and PHT groups, uric acid was associated with the % water and BMI in obese. Finally, uric acid was associated with % water and the WC in the abdominal obesity, and HT groups' .The body water percentage is an important indicator to development of oxidative stress in this population.

Hiperuricemia y progresión del compromiso cardiorrenal crónico / Hyperuricemia and progression of chronic cardiorenal compromise

Con el objetivo de determinar si la hiperuricemia está asociada con la progresión del compromiso cardiorrenal crónico (CCC) se realizó un estudio de cohorte retrospectiva que incluyó a 103 pacientes en quienes se definió CCC como presencia simultánea de enfermedad renal crónica (ERC) y enfermedad cardiaca crónica (ECC). Se definió progresión de la ERC como la reducción del 50% de la tasa de filtración glomerular estimada por la ecuación MDRD-4. Se definió hiperuricemia como niveles de ácido úrico basal mayor que 7 mg/dL. Ninguna de las variables estudiadas demostró asociación con la progresión del CCC o la ECC. Las variables que mostraron ser factores independientes de progresión de la ERC fueron hiperuricemia basal (HR 4,41; IC 95%: 1,02û18,94) y PAS en el seguimiento (HR 1,05; IC 95%: 1,01û1,09). Se concluye que la hiperuricemia mostró ser un factor de riesgo independiente de progresión de ERC en pacientes con CCC...

In order to determine whether hyperuricemia is associated with the progression of chronic cardiorenal compromise (CCC), a retrospective cohort study was performed which included 103 patients in whom CCC was defined as the simultaneous presence of chronic kidney disease (CKD) and chronic heart disease (CHD). CKD progression was defined as a 50% reduction of glomerular filtration rate estimated by the MDRD-4 equation. Hyperuricemia was defined as basal levels of uric acid mayor que 7 mg/dL. None of the studied variables showed association with the progression of CCC or CHD. Independent predictors of CKD progression were basal hyperuricemia (HR 4.41, 95% CI: 1.02-18.94) and SAP in follow-up (HR 1.05, 95% CI: 1.01-1.09). We conclude that hyperuricemia is an independent risk factor for the progression of CKD in patients with CCC...

Use of the probability of stone formation (PSF) score to assess stone forming risk and treatment response in a cohort of Brazilian stone formers

Introduction The aim was to confirm that PSF (probability of stone formation) changed appropriately following medical therapy on recurrent stone formers. Materials and Methods Data were collected on 26 Brazilian stone-formers. A baseline 24-hour urine collection was performed prior to treatment. Details of the medical treatment initiated for stone-disease were recorded. A PSF calculation was performed on the 24 hour urine sample using the 7 urinary parameters required: voided volume, oxalate, calcium, urate, pH, citrate and magnesium. A repeat 24-hour urine sample was performed for PSF calculation after treatment. Comparison was made between the PSF scores before and during treatment. Results At baseline, 20 of the 26 patients (77%) had a high PSF score (> 0.5). Of the 26 patients, 17 (65%) showed an overall reduction in their PSF profiles with a medical treatment regimen. Eleven patients (42%) changed from a high risk (PSF > 0.5) to a low risk (PSF < 0.5) and 6 patients reduced their risk score but did not change risk category. Six (23%) patients remained in a high risk category (> 0.5) during both assessments. Conclusions The PSF score reduced following medical treatment in the majority of patients in this cohort. .

The quest for a better understanding of chronic kidney disease complications: an update on uremic toxins / Em busca de uma melhor compreensão da doença renal crônica: uma atualização em toxinas urêmicas

Chronic kidney disease is characterized by a progressive reduction of glomerular filtration rate and/or the appearance of proteinuria, and subsequently the progressive retention of organic waste compounds called uremic toxins (UT). Over the last decades, a large number of such compounds have been identified and their effects on organs and tissues, especially the cardiovascular system, has been demonstrated. In this review, we present the current classification of UT, as proposed by the EUTox Group, and the effects of some of the probably most important UTs, such as phosphate, FGF-23, PTH, AGEs, indoxyl sulfate and para-cresyl sulfate. We provide an overview on therapeutic approaches aimed to increase their extracorporeal removal via convective and/or adsorptive strategies and to lower their intestinal production/ absorption via dietetic and pharmacological interventions. The recognition that multiple toxins contribute to the uremia supports the need for new therapeutic targets, with a potentially positive impact on CKD progression and survival.

A doença renal crônica (DRC) caracteriza-se pela redução progressiva da filtração glomerular e/ou presença de proteinúria, e subsequente retenção progressiva de compostos orgânicos, denominados toxinas urêmicas. Nas últimas décadas, um grande número destes compostos foi identificado, assim como seus efeitos adversos no organismo, sobretudo no sistema cardiovascular. Nesta revisão, apresentamos a classificação das toxinas urêmicas, proposta pelo grupo europeu de estudo em toxinas urêmicas (EUTox), e discutiremos os efeitos de algumas das principais toxinas, como ADMA, fosfato, FGF-23, PTH, AGEs, indoxil sulfato e para-cresil sulfato. Além disso, abordaremos as principais estratégias terapêuticas para aumentar a remoção das toxinas urêmicas por métodos convectivos e/ou adsortivos; e para diminuir a produção e absorção intestinal dessas toxinas por meio de intervenções dietéticas e farmacológicas, respectivamente. A compreensão de que múltiplas toxinas contribuem para a uremia expõe a necessidade de novos alvos-terapêuticos, com potencial impacto positivo na progressão da DRC e na sobrevida dos pacientes.

Transición epitelio-mesenquimática renal en un modelo experimental de Heperuricemia: participación de Nalp-3 y sus funciones canónicas y no-canónicas / Renal epithelial-mesenchymal transition in an experimental model of Hyperuricemia: participation Nalp-3 and its canonical and non-canonical functions

La fibrosis renal y la consecuente pérdida de las funciones del riñón son elementos comunes en la enfermedad renal crónica. La transición epitelio mesenquimatica (TEM) representa estadios tempranos del proceso de fibrosis. Recientemente se ha vinculado a la inmunidad innata en los procesos de injuria y fibrosis renal. Los pacientes con hiperuricemia presentan una mayor progresión a la enfermedad renal crónica, y mayor prevalencia de hipertensión arterial, induciendo fibrosis renal en modelos animales. No se conoce la participación de la inmunidad innata en la injuria renal inducida por ácido úrico. Para conocer la participación de la inmunidad innata en los procesos de TEM y fibrosis renal inducidos por ácido úrico se recurrió a un modelo desarrollado en rata Wistar macho con elevados niveles de ácido úrico (AOX+U). Para esto se suplementó la dieta con ácido oxónico al 2% (inhibidor de uricasa) y ácido úrico 2% durante 7 semanas. Dos grupos controles fueron considerados para comparar los hallazgos, un grupo con dieta estándar sin los agregados (C) y un segundo grupo control con suplemento de ácido oxónico y úrico, y además allopurinol en agua de bebida (ALL). Los niveles de ácido úrico y urea fueron testeados durante el tratamiento. A las 7 semanas los animales fueron sometidos a eutanasia y tejido renal fue obtenido para análisis de expresión proteica, análisis histológicos (fotónico y electrónico de transmisión) y para estudio mitocondrial: actividad de complejos de cadena respiratoria y respirometria de alta resolución mitocondrial.

SUMMARY: Chronic kidney disease (CKD) is associated with renal fibrosis and loss of kidney functions. Epithelial to mesenchimal transition (EMT) represents early stages of fibrosis. Currently the innate immunity has been associated with kidney injury and fibrosis. Hyperuricemic patients have more progression to CKD and higher prevalence of hypertension. Animals models have shown renal fibrosis induced by uric acid. It is not known the role of innate immunity in the uric acid induced damage in kidney. To describe the participation of the innate immunity in EMT and kidney fibrosis induced by uric acid we used a rat model with higher plasma levels of uric acid uric (AOX-U). These rats were feeding with oxonic acid 2% and uric acid 2% in regular chow during 7 weeks. Two control groups were included, “control group” (C) receiving regular chow without the supplements and the “ALL” group receiving not only the oxonic and uric acid supplement but also allopurinol in drinking water. The plasmatic uric acid and urea levels were checked during the follow-up. At 7 weeks the animals were euthanized and kidney tissue was harvested to protein expression analysis, histology and mitochondrial physiologic studies.

The effects of a diet formulation with oats, soybeans, and flax on lipid profiles and uricemia in patients with AIDS and dyslipidemia

Introduction Although the initiation of highly active antiretroviral therapy (HAART) is accompanied by an attenuation of viral load, metabolic disorders characterized by hyperglycemia, dyslipidemia, and lipodystrophy are often observed in patients under this treatment. Certain foods, such as oat bran, soy protein, and flaxseed, have been shown to improve a patient's lipid profile despite possible increases in uricemia. Thus, a bioactive compound was formulated using these foods to help patients with HIV/AIDS control metabolic disorders resulting from HAART. Methods An uncontrolled before and after study was performed. The total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and uric acid before and after 3 months of consuming the formulation were compared in patients. The compound was formulated such that 40g (the recommended daily intake) contained approximately 10g of flaxseed, 20g of oat bran, and 10g of textured soy protein. Results The study population consisted of 139 patients, 31 of whom were included in the final analysis. There were no significant variations between the laboratory results obtained before and after consumption of the compound. Conclusions The regular consumption of the formulation together with individualized dietary guidance did not reduce lipid levels and did not contribute to an increase in uricemia in the study group. However, new studies with higher doses of the foods that compose the formulation should be encouraged to investigate whether these foods can positively influence the lipid profiles of these patients. .