Uric acid and acute kidney injury in high-risk patients for developing acute kidney injury undergoing cardiac surgery: A prospective multicenter study.

PURPOSE: It is unclear whether preoperative serum uric acid (SUA) elevation may play a role in the development of acute kidney injury (AKI) associated with cardiac surgery (CSA-AKI). We conducted a cohort study to evaluate the influence of preoperative hyperuricemia on AKI in patients at high risk for developing SC-AKI. DESIGN: Multicenter prospective international cohort study. SETTING: Fourteen university hospitals in Spain and the United Kingdom. PARTICIPANTS: We studied 261 consecutive patients at high risk of developing CSA-AKI, according to a Cleveland score ≥ 4 points, from July to December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: AKIN criteria were used for the definition of AKI. Multivariable logistic regression models and propensity score-matched pairwise analysis were used to determine the adjusted association between preoperative hyperuricemia (≥7 mg/dL) and AKI. Elevated preoperative AUS (≥7 mg/dL) was present in 190 patients (72.8%), whereas CSA-AKI occurred in 145 patients (55.5%). In multivariable logistic regression models, hyperuricemia was not associated with a significantly increased risk of AKI (adjusted Odds Ratio [OR]: 1.58; 95% confidence interval [CI]: 0.81-3; P = .17). In propensity score-matched analysis of 140 patients, the hyperuricemia group experienced similar adjusted odds of AKI (OR 1.05, 95%CI 0.93-1.19, P = .37). CONCLUSIONS: Hyperuricemia was not associated with an increased risk of AKI in this cohort of patients undergoing cardiac surgery at high risk of developing CSA-AKI.

Assessing levels of uric acid and other cardiovascular markers in prehypertensive and hypertensive adults.

INTRODUCTION: Although some studies have reported the association between uric acid (UA) and hypertension, evidence on prehypertension is still lacking. Therefore, the objective of this study was to determine the levels of UA and other cardiovascular markers among prehypertensive and hypertensive patients and assess their risk for developing arterial hypertension. METHODS: 157 individuals were recruited: 67 normotensive, 23 pre-hypertensive and 67 hypertensive. Blood samples were collected to measure biochemical parameters and anthropometric measurements and blood pressure were evaluated. We calculated the product of lipid accumulation and the visceral adiposity index to assess cardiovascular risk. RESULTS: Our data showed an increase in UA levels in normotensives (4.9±1.3mg/dL), prehypertensives (5.2±1.3mg/dL) and hypertensives (5.9±1.6mg/dL) (p=0.004). We found a higher frequency of hyperuricemia in the hypertensive group (34.3%) than in the normotensive group (13.4%, p<0.05). Hypertensive volunteers had lower levels of HDL-C (p=0.004 and p=0.003) and higher body mass indexes (p<0.001 and p=0.007), glucose (p<0.001 and p=0.033), triglycerides (p=0.001 and p=0.005), visceral adiposity index (p<0.001 and p=0.002) and lipid accumulation product (p<0.001 and p=0.007) than normotensive and prehypertensive participants. We also observed that individuals with UA≥6.2mg/dL had an increased risk of hypertension of 4.77 (p=0.003) compared to individuals with levels≤4.3mg/dL. CONCLUSION: Our results showed that UA is associated with increased blood pressure and unfavorable changes in anthropometric and biochemical parameters, which represent risk factors for hypertension and cardiovascular diseases.

Tratamiento farmacológico de la litiasis renal: medicamentos actuales y monitorización del pH urinario / Pharmacologic treatment of kidney stones: Current medication and pH monitoring

La nefrolitiasis es una enfermedad urológica de prevalencia mundial asociada a una importante morbilidad y malestar para el paciente. El tratamiento actual de los cálculos renales se basa en intervenciones quirúrgicas y farmacológicas. Aunque la cirugía puede ser necesaria en casos determinados, el tratamiento farmacológico es una opción más asequible, fácilmente disponible y menos invasiva para el paciente. Se realizó una revisión exhaustiva para resumir la bibliografía disponible sobre las estrategias de manejo farmacológico de los principales tipos de litiasis: oxalato cálcico, fosfato cálcico, ácido úrico, estruvita y cistina. La regulación de factores como el pH urinario, la cristalización de los cálculos y los trastornos metabólicos del paciente que precipitan el desarrollo y el crecimiento de los cálculos es fundamental para estos enfoques terapéuticos. Esta revisión hace hincapié en las opciones farmacológicas disponibles para el tratamiento según el tipo de litiasis y destaca la importancia de un tratamiento médico personalizado para cada paciente, aspecto que debe ser tenido en cuenta por todos los médicos. (AU)

Nephrolithiasis is a globally prevalent urologic condition associated with significant morbidity and patient discomfort. Current management of kidney stones includes both surgical and pharmacologic interventions. Though surgery may be necessary under certain circumstances, pharmacologic treatment is a more affordable, readily available, and a less invasive option for patients. A comprehensive scoping review was conducted to summarize the available literature on the pharmacologic strategies for managing the predominant stone types including calcium oxalate, calcium phosphate, uric acid, struvite, and cystine stones. Central to these therapeutic approaches is the regulation of factors such as urine pH, stone crystallization, and patient metabolics that precipitate stone development and growth. This review highlights the pharmacological options available for treating each kidney stone type, emphasizing the importance of patient tailored medical management that should be considered by every physician. (AU)

[Gout, beyond the joint: How should we treat it?] / La gota, más allá de la articulación: ¿cómo debemos tratarla?

Gout is a disease caused by the chronic deposition of monosodium urate crystals. Its clinical presentation as an acute, self-limiting arthritis and the belief that it is a banal, self-inflicted disease have led to its poor management. Despite advances in the knowledge of the disease and the simplicity of its management, no more than 30% of patients are well treated. In Spain, the prevalence of gout is 2.5% and its incidence is increasing. In the following article we will review the pathogenesis of gout and hyperuricaemia, highlighting the greater weight of genetics and renal function over diet. We will look at the consequences of crystal deposition. Gout, in addition to its joint presentation and renal involvement, has been shown to be an independent cardiovascular risk factor. Hypouricemic therapy is the most important treatment, as it is the one that dissolves the crystals and cures the disease. This requires the sustained achievement of uricemia levels below 6mg/dl. We will also review preventive and flares treatment, as well as the role of patient education in terms of both lifestyle and dietary habits and adherence to pharmacological treatment.

Pharmacologic treatment of kidney stones: Current medication and pH monitoring.

Nephrolithiasis is a globally prevalent urologic condition associated with significant morbidity and patient discomfort. Current management of kidney stones includes both surgical and pharmacologic interventions. Though surgery may be necessary under certain circumstances, pharmacologic treatment is a more affordable, readily available, and a less invasive option for patients. A comprehensive scoping review was conducted to summarize the available literature on the pharmacologic strategies for managing the predominant stone types including calcium oxalate, calcium phosphate, uric acid, struvite, and cystine stones. Central to these therapeutic approaches is the regulation of factors such as urine pH, stone crystallization, and patient metabolics that precipitate stone development and growth. This review highlights the pharmacological options available for treating each kidney stone type, emphasizing the importance of patient tailored medical management that should be considered by every physician.

Asociación del nivel de ácido úrico en suero con los beneficios del control intensivo de la presión arterial / Association of serum uric acid with benefits of intensive blood pressure control

Introducción y objetivos: El control intensivo de la presión arterial sistólica (PAS) mejora los resultados de la estrategia de control de la presión arterial en el ensayo STEP con pacientes ancianos hipertensos. Sin embargo, se desconoce si los niveles de ácido úrico pueden afectar los beneficios del control intensivo de la PAS. Métodos: El ensayo STEP fue un estudio controlado y aleatorizado que comparó el efecto del control intensivo (PAS objetivo de 110 o <130mm Hg) frente al tratamiento estándar (PAS objetivo de 130 o <150mm Hg) de la PAS en pacientes chinos hipertensos de entre 60 y 80 años. El objetivo primario incluyó un conjunto de eventos asociados a la enfermedad cardiovascular. Se utilizaron los modelos de curvas spline cúbicas restringidas y análisis de subgrupos para estudiar si los efectos del control intensivo de la PAS difieren en función las concentraciones basales de ácido úrico. Ambos modelos se basaron en la subdistribución de riesgos de Fine-Gray para el análisis del objetivo primario y los objetivos secundarios. El modelo de regresión de Cox se utilizó para el análisis de muerte por cualquier causa. También se analizaron las concentraciones de ácido úrico durante el seguimiento. Resultados: El riesgo del objetivo primario se incrementó con el incremento de la concentración de ácido úrico tanto en el grupo de tratamiento intensivo como en el de tratamiento estándar. Los pacientes bajo tratamiento intensivo mostraron menor subdistribución (ajustada de forma multivariable) del cociente de riesgo para el objetivo primario, aunque con un amplio solapamiento del IC 95%. La estratificación de pacientes por terciles de concentración de ácido úrico mostró un CR de 0,55 (IC95%, 0,36-0,86; p=0,008) para el tercil 1 (ácido úrico <303,0μmol/l), de 0,80 (IC95%, 0.56-1.14; p=0,22) para el tercil 2 (AcU 303,0 a <375,8μmol/l) y de 0,86 (IC95%, 0,60–1,21; p=0,39) para el tercil 3 (AcU ≥ 375,8μmol/l); p=0,29 para la interacción...(AU)

Introduction and objectives: Intensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether the serum uric acid concentration at baseline alters the benefits of intensive SBP control is unknown. Methods: The STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to<130mmHg) and standard (SBP target of 130 to <150mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. This post hoc analysis was performed to examine whether the effects of intensive SBP intervention differed by the baseline uric acid concentration using 2 models: restricted cubic spline curves and subgroup analyses, both based on the Fine-Gray subdistribution hazard model in the analysis of the primary outcome and secondary outcomes (excluding all-cause death). In the analysis of all-cause death, the Cox regression model was used. We also examined the change in the follow-up uric acid concentrations. Results: Overall, the risk of the primary outcome rose as the cumulative uric acid concentration increased in both the intensive and standard treatment groups. Patients with intensive treatment had a lower multivariable-adjusted subdistribution hazard ratio for the primary outcome, but with a wide overlap of 95%CI. Next, we stratified patients according to their baseline uric acid concentration (tertile 1 [T1], <303.0μmol/L; tertile 2 [T2], 303.0 to <375.8μmol/L; and tertile 3 [T3], ≥375.8μmol/L). Subgroup analyses using tertiles provided HRs and 95%CI in T1 (HR, 0.55; 95%CI, 0.36–0.86; P=.008), T2 (HR, 0.80; 95%CI, 0.56–1.14; P=.22) and T3 (HR, 0.86; 95%CI, 0.60–1.21; P=.39), with an interaction P value of .29. The results for most of the secondary outcomes followed the same trends...(AU)

Correlación del ácido úrico con el grosor de la íntima media de la carótida en adolescentes con obesidad / Correlation of uric acid with carotid intima media thickness in obese adolescents

Introducción: la obesidad en la población pediátrica es un problema de salud pública. Se ha demostrado la correlación del ácido úrico y el grosor de la íntima media de la carótida en adultos. Objetivo: identificar la correlación del ácido úrico y el grosor de la íntima media de la carótida en adolescentes con obesidad. Material y métodos: se realizó un estudio observacional, transversal. Se incluyeron pacientes de diez a 16 años con diagnóstico de obesidad. Se determinó ácido úrico, perfil de lípidos y grosor de la íntima media carotidea. En el análisis estadístico, se correlacionó el grosor de la íntima media carotídea con los niveles de ácido úrico a través del coeficiente de correlación de Spearman. Resultados: se incluyeron 169 adolescentes con una mediana para la edad de 13 años, sin predominio de sexo. Se identificó una correlación positiva del ácido úrico con el grosor de la íntima media carotídea (r = 0,242, p = 0,001). Al estratificarse de acuerdo con el sexo, no hubo correlación en las mujeres (r = -0,187, p = 0,074), mientras que en los hombres aumentó (r = 0,36, p = 0,001) y por estadio puberal, los adolescentes varones púberes tuvieron una correlación positiva (p = 0,384, p = 0,002). Conclusión: se identificó una correlación positiva débil entre el grosor de la íntima de la carótida y el ácido úrico en adolescentes con obesidad. (AU)

Introduction: obesity in the pediatric population is a public health problem. The correlation of uric acid and carotid intima media thickness in adults has been demonstrated.Objective: to identify the correlation of uric acid and carotid intima media thickness in adolescents with obesity.Material and methods: an observational, cross-sectional study was carried out. Patients aged ten to 16 years with a diagnosis of obesity were included. Uric acid, lipid profile and carotid intima media thickness were determined. In relation to the statistical analysis, carotid intima media thickness was correlated with uric acid levels through Spearman's correlation coefficient. Results: one hundred and sixty-nine adolescents were included with a median age of 13 years, without predominance of sex. A positive correlation of uric acid with carotid intima media thickness was identified (r = 0.242, p = 0.001). When stratified according to sex, there was no correlation in women (r = -0.187, p = 0.074), while in men it increased (r = 0.36, p = 0.001) and by pubertal stage, pubertal male adolescents had a positive correlation (p = 0.384, p = 0.002).Conclusion: a weak positive correlation was identified between carotid intimal thickness and uric acid in obese adolescents. (AU)

[Correlation of uric acid with carotid intima media thickness in obese adolescents]. / Correlación del ácido úrico con el grosor de la íntima media de la carótida en adolescentes con obesidad.

Introduction: Introduction: obesity in the pediatric population is a public health problem. The correlation of uric acid and carotid intima media thickness in adults has been demonstrated. Objective: to identify the correlation of uric acid and carotid intima media thickness in adolescents with obesity. Material and methods: an observational, cross-sectional study was carried out. Patients aged ten to 16 years with a diagnosis of obesity were included. Uric acid, lipid profile and carotid intima media thickness were determined. In relation to the statistical analysis, carotid intima media thickness was correlated with uric acid levels through Spearman's correlation coefficient. Results: one hundred and sixty-nine adolescents were included with a median age of 13 years, without predominance of sex. A positive correlation of uric acid with carotid intima media thickness was identified (r = 0.242, p = 0.001). When stratified according to sex, there was no correlation in women (r = -0.187, p = 0.074), while in men it increased (r = 0.36, p = 0.001) and by pubertal stage, pubertal male adolescents had a positive correlation (p = 0.384, p = 0.002). Conclusion: a weak positive correlation was identified between carotid intimal thickness and uric acid in obese adolescents.

Introducción: Introducción: la obesidad en la población pediátrica es un problema de salud pública. Se ha demostrado la correlación del ácido úrico y el grosor de la íntima media de la carótida en adultos. Objetivo: identificar la correlación del ácido úrico y el grosor de la íntima media de la carótida en adolescentes con obesidad. Material y métodos: se realizó un estudio observacional, transversal. Se incluyeron pacientes de diez a 16 años con diagnóstico de obesidad. Se determinó ácido úrico, perfil de lípidos y grosor de la íntima media carotidea. En el análisis estadístico, se correlacionó el grosor de la íntima media carotídea con los niveles de ácido úrico a través del coeficiente de correlación de Spearman. Resultados: se incluyeron 169 adolescentes con una mediana para la edad de 13 años, sin predominio de sexo. Se identificó una correlación positiva del ácido úrico con el grosor de la íntima media carotídea (r = 0,242, p = 0,001). Al estratificarse de acuerdo con el sexo, no hubo correlación en las mujeres (r = -0,187, p = 0,074), mientras que en los hombres aumentó (r = 0,36, p = 0,001) y por estadio puberal, los adolescentes varones púberes tuvieron una correlación positiva (p = 0,384, p = 0,002). Conclusión: se identificó una correlación positiva débil entre el grosor de la íntima de la carótida y el ácido úrico en adolescentes con obesidad.

Does uric acid-lowering treatment slow the progression of chronic kidney disease? A meta-analysis of randomized controlled trials / ¿El tratamiento para reducir el ácido úrico retarda la progresión de la enfermedad renal crónica? Un metaanálisis de ensayos controlados aleatorizados

Introduction: Hyperuricemia has been proposed as an independent factor in the development and progression of chronic kidney disease (CKD). However, the effect of uric acid-lowering therapies on delaying CKD progression is still uncertain. Therefore, this systemic review aims to assess the effect of uric acid-lowering therapies on renal outcomes in pre-dialysis CKD patients. Methods: PubMed, Cochrane Library, and Lilacs databases were searched until April 24, 2021, for randomized clinical trials of CKD patients on uric acid-lowering treatment with xanthine-oxidase (XO) inhibitors. The weighted mean difference (WMD) or standard mean difference (SMD) with confidence interval (CI) were pooled using a random-effects model. Results: Among 567 studies found, eighteen met the inclusion criteria (n=2463 participants). Compared to the patient's control group, the WMD for the glomerular filtration ratio (GFR) and serum creatinine changes of the treated group was 2.02ml/min/1.73m2 (95%CI 0.41 to 3.63, P=0.014) and −0.19mg/dl (95%CI −0.34 to −0.04, I2=86.2%, P=0.011), respectively. Subgroup analyses showed that the difference in follow-up time and CKD population type in the studies may explain the controversy about the role of uric acid-lowering therapies in CKD progression. The GFR and creatinine outcomes analysis by types of XO inhibitors showed no difference between the control and treated groups. Uric acid-lowering therapies were strongly associated with decreased serum uric acid and urinary protein–creatinine ratio and urinary albumin–creatinine ratio. (AU)

Antecedentes: La hiperuricemia se ha propuesto como un factor independiente en el desarrollo y la progresión de la enfermedad renal crónica (ERC). Sin embargo, el efecto de las terapias para reducir el ácido úrico en el retraso de la progresión de la ERC aún es incierto. Por lo tanto, esta revisión sistémica tiene como objetivo evaluar el efecto de los tratamientos para reducir el ácido úrico sobre los resultados renales en pacientes con ERC antes de la diálisis. Métodos: Se realizaron búsquedas en las bases de datos de PubMed, Cochrane Library y Lilacs hasta el 24 de abril de 2021 en busca de ensayos clínicos aleatorizados de pacientes con ERC en tratamiento para reducir el ácido úrico con inhibidores de la xantina-oxidasa (XO). La diferencia de medias ponderada (DMP) o la diferencia de medias estándar (DME) con el intervalo de confianza (IC) se agruparon mediante un modelo de efectos aleatorizados. Resultados: Entre los 567 estudios encontrados, 18 cumplieron los criterios de inclusión (n=2.463 participantes). En comparación con los pacientes del grupo control, la DMP para la tasa de filtración glomerular (TFG) y los cambios en la creatinina sérica del grupo tratado fueron de 2,02ml/min/1,73m2 (IC del 95%: 0,41 a 3,63, P=0,014) y −0,19mg/dl (IC del 95%: −0,34 a −0,04, I2=86,2%, P=0,011), respectivamente. Los análisis de subgrupos mostraron que la diferencia en el tiempo de seguimiento y el tipo de población con ERC en los estudios puede explicar la controversia sobre el papel de las terapias para reducir el ácido úrico en la progresión de la ERC. El análisis de resultados de TFG y de creatinina por tipos de inhibidores de la XO no mostró diferencias entre el grupo control y el grupo tratado. Las terapias para reducir el ácido úrico se asociaron fuertemente con una disminución del ácido úrico sérico y de la relación proteína-creatinina urinaria y la relación albúmina-creatinina urinaria. (AU)

NRBP1 modulates uric acid transporter ABCG2 expression by activating the Wnt/B-catenin pathway in HK-2 cells / NRBP1 regula la expresión del transportador de ácido úrico ABCG2 en las células HK-2 mediante la activación de la vía Wnt/B-catenina

Background: Nuclear receptor binding protein 1 (NRBP1) and ATP-binding cassette subfamily G member 2 (ABCG2) was the gout risk gene and high-capacity urate exporter respectively. However, the relationship between NRBP1 and ABCG2 and the underlying molecular mechanism contributing to these associations are unknown. Methods: Firstly, the efficiency of the overexpression and knockdown of NRBP1 was confirmed by western blot. Next, the effect of NRBP1 overexpression and knockdown on the expression of ABCG2, organic anion transporter 1 (OAT1), glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) was detected by qRT-PCR and western blot. At the same time, the cellular location of ABCG2 and its expression after NRBP1 overexpression and knockdown was tested by immunofluorescence (IF) staining. Then, the mechanism of NRBP1 modulates ABCG2 expression was evaluated by western blot with or without the β-catenin inhibitor (21H7). Results: The lentivirus system was used to generate stable NRBP1 overexpression, while the plasmids carrying a NRBP1 siRNA was generated to knockdown NRBP1 expression in HK-2 cells. Meanwhile, the overexpression of NRBP1 significantly decreased the mRNAs and proteins expression of GLUT9 and URAT1, while the knockdown of NRBP1 increased the mRNAs and proteins expression of ABCG2 significantly. In addition, the NRBP1 modulates the expression of ABCG2 was by ctivating the Wnt/β-catenin pathway in HK-2 cells according to the IF and western blot results. Conclusion: Taken together, our study demonstrated that NRBP1 inhibition played an essential role in attenuating hyperuricemia and gout by upregulation of ABCG2 via Wnt/β-catenin signaling pathway in HK-2 cells. (AU)

Antecedentes: La proteína de unión al receptor nuclear 1 (NRBP1) y el miembro G de la subclase ATP binding Box 2 (ABCG2) son los genes de riesgo de gota y los genes de salida de urato de alto rendimiento, respectivamente. Sin embargo, se desconoce la relación entre NRBP1 y ABCG2, y los posibles mecanismos moleculares que conducen a estas asociaciones. Métodos: En primer lugar, la sobreexpresión y el knockout de NRBP1 fueron confirmados por Western-blot. Los efectos de la sobreexpresión y knockout de NRBP1 en la expresión de ABCG2, transportador de aniones orgánicos 1 (OAT1), transportador de glucosa 9 (GLUT9) y transportador de ácido úrico 1 (URAT1) fueron detectados por qRT-PCR y Western-blot. Mientras tanto, la localización y expresión de ABCG2 después de la sobreexpresión y knockout de NRBP1 fueron detectadas por inmunofluorescencia (IF). Luego, el efecto regulador de NRBP1 sobre la expresión de ABCG2 fue estudiado por Western-blot y comparado con el inhibidor de la β-catenina (21H7). Resultados: El sistema lentiviral indujo una sobreexpresión estable de NRBP1, mientras que el plásmido portador de SiRNA NRBP1 inhibió la expresión de NRBP1 en las células HK-2. Mientras tanto, la sobreexpresión de NRBP1 redujo significativamente la expresión de ARNm y proteínas de GLUT9 y URAT1, mientras que el knockout de NRBP1 aumentó significativamente la expresión de ARNm y proteínas de ABCG2. Además, de acuerdo con los resultados de IF y Western-blot, NRBP1 regula la expresión de ABCG2 activando la vía Wnt/β-catenina en las células HK-2. Conclusión: La inhibición del NRBP1 aumenta la regulación de ABCG2 a través de la vía de señalización Wnt/β-catenina, que desempeña un papel importante en la reducción de la hiperuricemia y la gota. (AU)

¿Debemos manejar la hiperuricemia asintomática para proteger al riñón?

Contexto: el ácido úrico es el producto final de la degradación de las purinas en los primates, en condiciones normales es un agente antioxidante endógeno y participa en varias vías fisiológicas, sin embargo, cuando los niveles séricos de urato se incrementan, estos participan en el desarrollo de diversas enfermedades. Desde el siglo XIX se conoce de la asociación entre hiperuricemia y daño renal, aunque ninguna guía de manejo recomienda el uso de fármacos hipouricemiantes en pacientes asintomáticos, en algunos casos especiales, el manejo farmacológico beneficiará a pacientes con hiperuricemia, brindando protección al riñón y disminuyendo el riesgo de desarrollar enfermedad renal terminal. Objetivo: describir la relación entre hiperuricemia y daño renal, y analizar los casos en los que el manejo de esta condición con medicamentos resultará en un beneficio para el riñón de los pacientes. Metodología: revisión de la literatura sobre la participación de la hiperuricemia en el daño renal y análisis de los artículos revisados. Resultados: el manejo de la hiperuricemia asintomática puede proteger el riñón en algunas situaciones específicas. Conclusiones: hay situaciones específicas para la disminución de los niveles séricos de ácido úrico.

Background: Uric acid is the end product of purine degradation in primates, under normal conditions it is an endogenous antioxidant agent and participates in several physiological pathways. However, when serum urate levels are increased, they participate in the development of various diseases. Since the nineteenth century, the association between hyperuricemia and kidney damage has been known. Although no management guideline recommends the use of hypouricemic drugs in asymptomatic patients, in some special cases pharmacological management will benefit patients with hyperuricemia, providing protection to the kidney and decreasing the risk of developing end-stage renal disease. Purpose: To describe the relationship between hyperuricemia and kidney damage, and to analyze the cases in which the management of this condition with medications will result in a benefit for the kidney of patients. Methodology: Review of the literature on the involvement of hyperuricemia in kidney damage, analysis of the reviewed articles. Results: Management of asymptomatic hyperuricemia may protect the kidney in some specific situations. Conclusions: There are specific situations for the decrease of serum uric acid levels.

The relationship between uric acid levels and graft function in renal transplant patients who discontinued steroid therapy / Relación entre niveles de ácido úrico y función del injerto en pacientes de trasplante renal que interrumpieron la terapia con esteroides

ABSTRACT Introduction: High uric acid levels are commonly encountered in kidney transplant recipients, and can be associated with allograft dysfunction. Our study aims to examine the relationship between UA levels and graft function in patients discontinuing steroids. Methods: In this single-center-retrospective study, 56 patients discontinued steroid therapy from among 678 RT patients transplanted from living donors between 1999-2020 were included. The mean age of the study group was 45.8±8.8 years. Causes of steroid discontinuation, creatinine levels concurrent with uric acid levels before and after steroid discontinuation (mean 3.9 ± 2.1 years), acute rejection numbers, demographics, durations of dialysis and transplantation, medications, laboratory data, human leukocyte antigen (HLA) mismatch numbers, blood-pressure (BP), body mass index, delayed acute rejection (DAR) numbers (3 months post-transplantation) were all recorded. Results: Creatinine and uric acid levels were seen to have increased after steroid discontinuation, there was a significant relationship between them (p<0.001). Statistically significant correlation was found between increased creatinine levels after steroid discontinuation and graft survival with higher HLA mismatch; 39 (69.6%) patients with mismatch ≥2, and 17 patients with mismatch <2 (30.4%) (p=0.049) . No significant relationship was found between DAR numbers before and after steroid discontinuation, and creatinine levels after steroid discontinuation. Conclusion: Per model obtained as a result of multivariate linear analysis, hyperuricemia and HLA mismatch numbers (p= 0.048 and p= 0.044, respectively) are independent predictive factors for graft dysfunction in patients discontinuing steroids. Accordingly, negative effects of modeling should be kept in mind for long-term graft survival in patients who plan to continue with steroid-sparing regimens.

RESUMEN Introducción: Con frecuencia se registran niveles elevados de ácido úrico en receptores de trasplantes renales que pueden estar asociados a disfunción de aloinjerto. El presente estudio tiene por objeto examinar la relación entre los niveles de AU y la función del injerto en pacientes que interrumpieron la terapia con esteroides. Métodos: En este estudio retrospectivo en un solo centro participaron 56 pacientes con interrupción de la terapia con esteroides de un total de 678 pacientes con TR receptores de trasplante de donantes vivos en el período 1999-2020. La edad promedio de la población de estudio fue de 45,8 ± 8,8 años. En el estudio se registraron causas de la interrupción de la terapia con esteroides, niveles de creatinina concurrentes con niveles de ácido úrico antes y después de la interrupción de la terapia con esteroides (promedio de 3,9 ± 2,1 años), números de rechazo agudo, datos demográficos, duraciones del período de diálisis y trasplante, medicación (uso de inmunosupresores, antihipertensivos), datos de laboratorio, números de desajuste del antígeno leucocitario humano (HLA), presión arterial (PA), índice de masa corporal, números de rechazo agudo retardado (DAR) (3 meses después del trasplante). Resultados: Se observó que los niveles de creatinina y ácido úrico aumentaron tras interrumpir la administración de esteroides, con una relación significativa entre ambos (p<0,001). Se identificó una correlación estadísticamente significativa entre el aumento en los niveles de creatinina tras la interrupción de la terapia de esteroides y la supervivencia del injerto con un mayor desajuste de HLA: 39 pacientes (el 69,6%) con desajuste ≥2 y 17 (el 30,4%) pacientes con desajuste <2 (p=0,049). No se encontró una relación significativa entre el número de DAR antes y después de la interrupción del tratamiento con esteroides, así como en los niveles de creatinina tras la interrupción de la terapia con esteroides. Conclusión: De acuerdo con el modelo obtenido como resultado del análisis lineal multivariable, la hiperuricemia y los números de desajuste de HLA (p=0,048 y p=0,044, respectivamente) constituyen factores predictivos independientes para la disfunción del injerto en pacientes que interrumpen la terapia con esteroides. En consecuencia, se deben tener en cuenta los efectos negativos del modelado para la supervivencia del injerto a largo plazo en pacientes que planean proseguir con regímenes con reducción de la administración esteroides.

Association of serum uric acid with benefits of intensive blood pressure control.

INTRODUCTION AND OBJECTIVES: Intensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether the serum uric acid concentration at baseline alters the benefits of intensive SBP control is unknown. METHODS: The STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to<130mmHg) and standard (SBP target of 130 to <150mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. This post hoc analysis was performed to examine whether the effects of intensive SBP intervention differed by the baseline uric acid concentration using 2 models: restricted cubic spline curves and subgroup analyses, both based on the Fine-Gray subdistribution hazard model in the analysis of the primary outcome and secondary outcomes (excluding all-cause death). In the analysis of all-cause death, the Cox regression model was used. We also examined the change in the follow-up uric acid concentrations. RESULTS: Overall, the risk of the primary outcome rose as the cumulative uric acid concentration increased in both the intensive and standard treatment groups. Patients with intensive treatment had a lower multivariable-adjusted subdistribution hazard ratio for the primary outcome, but with a wide overlap of 95%CI. Next, we stratified patients according to their baseline uric acid concentration (tertile 1 [T1], <303.0µmol/L; tertile 2 [T2], 303.0 to <375.8µmol/L; and tertile 3 [T3], ≥375.8µmol/L). Subgroup analyses using tertiles provided HRs and 95%CI in T1 (HR, 0.55; 95%CI, 0.36-0.86; P=.008), T2 (HR, 0.80; 95%CI, 0.56-1.14; P=.22) and T3 (HR, 0.86; 95%CI, 0.60-1.21; P=.39), with an interaction P value of .29. The results for most of the secondary outcomes followed the same trends. CONCLUSIONS: There was no evidence that the benefit of the intensive SBP control differed by baseline uric acid concentrations. This trial was registered at ClinicalTrial.gov (Identifier: NCT03015311).

Low serum uric acid levels and levodopa-induced dyskinesia in Parkinson's disease / Níveis séricos baixos de ácido úrico e discinesia induzida por levodopa na doença de Parkinson

Abstract Background Levodopa is the most used and effective medication for motor symptoms of Parkinson disease (PD), its long-term use is associated with the appearance of levodopa-induced dyskinesia (LID). Uric acid (UA) is believed to play an important neuroprotective role in PD. Objective To investigate if serum UA levels are related with the presence of LIDs in PD patients. Also, we investigated the associations among UA levels and clinical features of PD. Methods We enrolled 81 PD patients (dyskinesia = 48; no dyskinesia = 33) in the present study. A blood sample was collected to evaluate serum UA levels, clinical evaluation included the following instruments: Montreal Cognitive Assessment (MoCA), Beck Depression Inventory II (BDI-II), MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr (HY), and the sub-item 4.1 of MDS-UPDRS IV (score ≥ 1). Additional relevant clinical information was obtained by a clinical questionnaire. Results Serum UA levels were lower in the dyskinesia group when compared with the no dyskinesia group. The same result was found in the UA levels of both men and women. The multivariate analysis showed lower uric acid levels were significantly associated with having dyskinesia (odds ratio [OR] = 0.424; 95% confidence interval [CI]: 0.221-0.746; p= 0.005). Additional analysis verified that serum UA levels are inversely correlated with depressive symptoms, disease duration, MDS-UPDRS IV and time spent with dyskinesia. A positive correlation was found with age at onset of PD symptoms. Conclusions The present study provides a possible role of serum UA levels in LID present in PD patients.

Resumo Antecedentes A levodopa é a medicação mais utilizada e eficaz para os sintomas motores da doença de Parkinson (DP); seu uso a longo prazo está associado ao aparecimento de discinesia induzida por levodopa (LID). Acredita-se que o ácido úrico desempenhe um importante papel neuroprotetor na DP. Objetivo Investigar se os níveis séricos de AU estão relacionados com a presença de LID em pacientes com DP. Além disso, investigamos as associações entre os níveis de AU e as características clínicas da DP. Métodos Foram incluídos 81 pacientes com DP (discinesia = 48; sem discinesia = 33) no presente estudo. Uma amostra de sangue foi coletada para avaliar os níveis séricos de AU, a avaliação clínica incluiu os seguintes instrumentos: Avaliação Cognitiva de Montreal (MoCA), Inventário de Depressão de Beck (BDI-II), MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr (HY) e o subitem 4.1 da MDS-UPDRS IV (escore ≥ 1). Informações clínicas relevantes adicionais foram obtidas por meio de um questionário clínico. Resultados Os níveis séricos de AU foram menores no grupo com discinesia quando comparados ao grupo sem discinesia. O mesmo resultado foi encontrado nos níveis de AU de homens e mulheres. A análise multivariada mostrou que níveis mais baixos de ácido úrico foram significativamente associados a ter discinesia (odds ratio [OR] = 0,424; intervalo de confiança (IC) de 95%: 0,221-0,746; p= 0,005). Análises adicionais verificaram que os níveis séricos de AU estão inversamente correlacionados com sintomas depressivos, duração da doença, MDS-UPDRS IV e tempo gasto com discinesia. Uma correlação positiva foi encontrada com a idade de início dos sintomas da DP. Conclusões O presente estudo fornece um possível papel dos níveis séricos de AU na LID presente em pacientes com DP.

NRBP1 modulates uric acid transporter ABCG2 expression by activating the Wnt/ß-catenin pathway in HK-2 cells.

BACKGROUND: Nuclear receptor binding protein 1 (NRBP1) and ATP-binding cassette subfamily G member 2 (ABCG2) was the gout risk gene and high-capacity urate exporter respectively. However, the relationship between NRBP1 and ABCG2 and the underlying molecular mechanism contributing to these associations are unknown. METHODS: Firstly, the efficiency of the overexpression and knockdown of NRBP1 was confirmed by western blot. Next, the effect of NRBP1 overexpression and knockdown on the expression of ABCG2, organic anion transporter 1 (OAT1), glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) was detected by qRT-PCR and western blot. At the same time, the cellular location of ABCG2 and its expression after NRBP1 overexpression and knockdown was tested by immunofluorescence (IF) staining. Then, the mechanism of NRBP1 modulates ABCG2 expression was evaluated by western blot with or without the ß-catenin inhibitor (21H7). RESULTS: The lentivirus system was used to generate stable NRBP1 overexpression, while the plasmids carrying a NRBP1 siRNA was generated to knockdown NRBP1 expression in HK-2 cells. Meanwhile, the overexpression of NRBP1 significantly decreased the mRNAs and proteins expression of GLUT9 and URAT1, while the knockdown of NRBP1 increased the mRNAs and proteins expression of ABCG2 significantly. In addition, the NRBP1 modulates the expression of ABCG2 was by ctivating the Wnt/ß-catenin pathway in HK-2 cells according to the IF and western blot results. CONCLUSION: Taken together, our study demonstrated that NRBP1 inhibition played an essential role in attenuating hyperuricemia and gout by upregulation of ABCG2 via Wnt/ß-catenin signaling pathway in HK-2 cells.

Does uric acid-lowering treatment slow the progression of chronic kidney disease? A meta-analysis of randomized controlled trials.

INTRODUCTION: Hyperuricemia has been proposed as an independent factor in the development and progression of chronic kidney disease (CKD). However, the effect of uric acid-lowering therapies on delaying CKD progression is still uncertain. Therefore, this systemic review aims to assess the effect of uric acid-lowering therapies on renal outcomes in pre-dialysis CKD patients. METHODS: PubMed, Cochrane Library, and Lilacs databases were searched until April 24, 2021, for randomized clinical trials of CKD patients on uric acid-lowering treatment with xanthine-oxidase (XO) inhibitors. The weighted mean difference (WMD) or standard mean difference (SMD) with confidence interval (CI) were pooled using a random-effects model. RESULTS: Among 567 studies found, eighteen met the inclusion criteria (n=2463 participants). Compared to the patient's control group, the WMD for the glomerular filtration ratio (GFR) and serum creatinine changes of the treated group was 2.02ml/min/1.73m2 (95%CI 0.41 to 3.63, P=0.014) and -0.19mg/dl (95%CI -0.34 to -0.04, I2=86.2%, P=0.011), respectively. Subgroup analyses showed that the difference in follow-up time and CKD population type in the studies may explain the controversy about the role of uric acid-lowering therapies in CKD progression. The GFR and creatinine outcomes analysis by types of XO inhibitors showed no difference between the control and treated groups. Uric acid-lowering therapies were strongly associated with decreased serum uric acid and urinary protein-creatinine ratio and urinary albumin-creatinine ratio. CONCLUSIONS: These findings suggest that uric acid-lowering treatment may slow CKD progress and reduce protein and albumin excretion. However, larger and properly powered randomized clinical trials with specific CKD populations are needed to confirm these findings.

Effects of liquid extract from Plinia cauliflora fruits residues on Chinese hamsters biochemical parameters / Efeitos do extrato líquido de resíduos de frutos de Plinia cauliflora sobre os parâmetros bioquímicos de hamsters chineses

Plinia cauliflora (Mart.) Kausel, popularly known as jabuticaba, is rich in polyphenols. Phenolic compounds exhibit several biological properties, which reflect on biomarkers such as biochemical parameters. In the present study, we evaluated the plasmatic levels of glucose, total cholesterol, HDL-cholesterol, triglycerides, and uric acid of Chinese hamsters fed for 45 days with a regular diet or cholesterol-enriched diet supplemented with a liquid extract obtained from P. cauliflora fruits residues standardized in ellagic acid and total phenolic compounds. The results showed that the concentrated extract obtained from jabuticaba residues increased the glycemia of animals fed with a regular diet and reduced the plasmatic uric acid levels of animals fed with a cholesterol-enriched diet. Since hyperuricemia is considered to be a significant risk factor of metabolic disorders and the principal pathological basis of gout, the liquid extract from P. cauliflora fruits residues would be a promising candidate as a novel hypouricaemic agent for further investigation.

Plinia cauliflora (Mart.) Kausel, popularmente conhecida como jabuticaba, é rica em polifenois. Os compostos fenólicos apresentam diversas propriedades biológicas, que refletem em biomarcadores, como os parâmetros bioquímicos. No presente estudo, avaliamos os níveis plasmáticos de glicose, colesterol total, HDL-colesterol, triglicerídeos e ácido úrico em hamsters chineses alimentados por 45 dias com dieta regular ou dieta enriquecida com colesterol suplementada com extrato líquido obtido de resíduos de frutos de P. cauliflora padronizado em ácido elágico e compostos fenólicos totais. Os resultados mostraram que o extrato concentrado obtido dos resíduos de jabuticaba aumentou a glicemia dos animais alimentados com dieta regular e reduziu os níveis plasmáticos de ácido úrico dos animais alimentados com dieta rica em colesterol. Uma vez que a hiperuricemia é considerada um fator de risco significativo de distúrbios metabólicos e a principal base patológica da gota, o extrato líquido dos resíduos de frutas de P. cauliflora seria um candidato promissor como um novo agente hipouricêmico para investigação posterior.

Effects of liquid extract from Plinia cauliflora fruits residues on Chinese hamsters biochemical parameters

Abstract Plinia cauliflora (Mart.) Kausel, popularly known as jabuticaba, is rich in polyphenols. Phenolic compounds exhibit several biological properties, which reflect on biomarkers such as biochemical parameters. In the present study, we evaluated the plasmatic levels of glucose, total cholesterol, HDL-cholesterol, triglycerides, and uric acid of Chinese hamsters fed for 45 days with a regular diet or cholesterol-enriched diet supplemented with a liquid extract obtained from P. cauliflora fruits residues standardized in ellagic acid and total phenolic compounds. The results showed that the concentrated extract obtained from jabuticaba residues increased the glycemia of animals fed with a regular diet and reduced the plasmatic uric acid levels of animals fed with a cholesterol-enriched diet. Since hyperuricemia is considered to be a significant risk factor of metabolic disorders and the principal pathological basis of gout, the liquid extract from P. cauliflora fruits residues would be a promising candidate as a novel hypouricaemic agent for further investigation.

Resumo Plinia cauliflora (Mart.) Kausel, popularmente conhecida como jabuticaba, é rica em polifenois. Os compostos fenólicos apresentam diversas propriedades biológicas, que refletem em biomarcadores, como os parâmetros bioquímicos. No presente estudo, avaliamos os níveis plasmáticos de glicose, colesterol total, HDL-colesterol, triglicerídeos e ácido úrico em hamsters chineses alimentados por 45 dias com dieta regular ou dieta enriquecida com colesterol suplementada com extrato líquido obtido de resíduos de frutos de P. cauliflora padronizado em ácido elágico e compostos fenólicos totais. Os resultados mostraram que o extrato concentrado obtido dos resíduos de jabuticaba aumentou a glicemia dos animais alimentados com dieta regular e reduziu os níveis plasmáticos de ácido úrico dos animais alimentados com dieta rica em colesterol. Uma vez que a hiperuricemia é considerada um fator de risco significativo de distúrbios metabólicos e a principal base patológica da gota, o extrato líquido dos resíduos de frutas de P. cauliflora seria um candidato promissor como um novo agente hipouricêmico para investigação posterior.

A Relação entre a Relação Ácido Úrico/Albumina e a Espessura Média-Intimal da Carótida em Pacientes com Hipertensão / The Relationship between Uric Acid/Albumin Ratio and Carotid Intima-Media Thickness in Patients with Hypertension

Resumo Fundamento A hipertensão causa inflamação subendotelial e disfunção na aterosclerose resultante. A espessura média-intimal da carótida (EMIC) é um marcador útil de disfunção endotelial e aterosclerose. A razão ácido úrico/albumina (RUA) emergiu como um novo marcador para prever eventos cardiovasculares. Objetivo Nosso objetivo foi investigar a associação da RUA com a EIMC em pacientes hipertensos. Método Duzentos e dezesseis pacientes hipertensos consecutivos foram incluídos neste estudo prospectivo. Todos os pacientes foram submetidos a ultrassonografia de carótida para classificar baixos (EMIC < 0,9 mm) e altos (EMIC≥0,9 mm) grupos de EMIC. A capacidade preditiva da RUA para EMIC alta foi comparada com o índice de inflamação imune sistêmica (IIS), razão neutrófilo/linfócito (RNL), razão plaqueta/linfócito (RPL) e razão proteína C reativa/albumina (RCA). Um valor de p bilateral <0,05 foi aceito como estatisticamente significativo. Resultados Os pacientes com EMIC alta eram mais velhos e tinham maior RUA, IIS, RNL e RCA do que baixo EMIC. Idade, RUA, IIS, RNL e RCA, mas não RPL, foram associados a EMIC alta. Na análise multivariada, idade, PCR, IIS e RUA foram preditores independentes de EMIC alta. A capacidade de discriminação de RUA foi maior do que ácido úrico, albumina, IIS, RNL e RCA, e RUA teve um ajuste de modelo maior do que essas variáveis. RUA teve maior melhoria aditiva na detecção de EMIC alta do que outras variáveis, conforme avaliado com melhoria de reclassificação líquida, MDI e estatísticas C. RUA também foi significativamente correlacionada com EMIC. Conclusão RUA pode ser usado para prever EMIC alta e pode ser útil para estratificação de risco em pacientes hipertensos.

Abstract Background Hypertension causes subendothelial inflammation and dysfunction in resulting atherosclerosis. Carotid intima-media thickness (CIMT) is a useful marker of endothelial dysfunction and atherosclerosis. The uric acid to albumin ratio (UAR) has emerged as a novel marker for predicting cardiovascular events. Objective We aimed to investigate the association of UAR with CIMT in hypertensive patients. Methods Two hundred sixteen consecutive hypertensive patients were enrolled in this prospective study. All patients underwent carotid ultrasonography to classify low (CIMT < 0.9 mm) and high (CIMT ≥ 0.9 mm) CIMT groups. The predictive ability of UAR for high CIMT was compared with systemic immune inflammation index (SII), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and C-reactive protein/albumin ratio (CAR). A two-sided p-value <0.05 was accepted as statistically significant. Results Patients with high CIMT were older and had higher UAR, SII, NLR, and CAR than low CIMT. Age, UAR, SII, NLR, and CAR, but not PLR, were associated with high CIMT. In multivariable analysis, age, CRP, SII, and UAR were independent predictors of high CIMT. The discrimination ability of UAR was higher than uric acid, albumin, SII, NLR, and CAR, and UAR had a higher model fit than those variables. UAR had higher additive improvement in detecting high CIMT than other variables, as assessed with net-reclassification improvement, IDI, and C-statistics. UAR was also significantly correlated with CIMT. Conclusion UAR might be used to predict high CIMT and might be useful for risk stratification in hypertensive patients.