Lower Serum Uric Acid Levels Research Articles

Antioxidant Effect of Taurine on Chronic Heat-Stressed Broilers.

The purpose of this study was to investigate the effects of taurine on blood indices of broilers with chronic heat stress and to provide theoretical basis for the application of taurine in the anti-chronic heat stress of broilers. In the test, 240 AA + broilers at 7days of age were randomly divided into five groups: the normal temperature control group (24±2°C) in group C, the heat stress control group (34±2°C) in HS group, and the LTau, MTau, and HTau groups in heat under stress conditions, 0.5g/L, 2g/L, and 8g/L taurine, were added to the drinking water, and each group was repeated three times. After 2weeks of feeding at normal temperature, heat stress began. The test period was 4weeks. Blood was collected at 6 h, 12 h, 7 d, 14 d, 21 d, and 28 d after heat stress, and serum was separated. The results showed that compared with the HS group, MTau significantly increased the total serum protein content (P<0.05), but the other groups were not significantly different (P>0.05). The MTau and HTau groups contained significantly lowered serum uric acid levels than the HS group (P<0.05). At 7d and 14d, the LTau, MTau, and HTau groups all exhibited significantly increased T3 and T4 concentrations (P<0.05). There was no significant difference between the groups at other times (P>0.05). Compared with the HS group, the MTau group contained significantly reduced serum CK activity, LDH activity, AST activity, and ALT activity (P<0.05). Compared with the LTau, MTau, and HTau groups, serum MDA content was significantly increased in the heat-stressed broilers (P<0.05). MTau group contained significantly increased T-AOC, SOD, CAT, and GSH-PX levels (P<0.05). The other groups were not significantly different (P>0.05). Compared with group C, serum HSP60 and HSP70 levels were significantly elevated in the HS group (P<0.05). Compared with the HS group, the LTau and MTau groups contained significantly increased serum HSP60 and HSP70 concentrations (P<0.05), but the other groups were not significantly different (P>0.05). In conclusion, taurine can alleviate the symptoms of chronic heat stress of broilers, regulate the metabolism of the body, and improve the antioxidant activity of the body.

Effects of Taurine on Serum Indexes of Broilers with Chronic Heat Stress.

The aim of this study was to investigate the effects of taurine on tissue injury, protein metabolism, and basal metabolism of broilers after chronic heat stress by detecting serum physiological and biochemical indices. In the test, 240 AA + broilers at 7days of age were randomly divided into five groups: the normal temperature control group (24±2°C) in group C, the heat stress control group (34±2°C) in HS group, and the LTau, MTau, and HTau groups in heat under stress conditions, 0.5, 2, and 8g/L taurine were added to the drinking water, and each group was repeated three times. After 2weeks of feeding at normal temperature, heat stress began. The test period was 4weeks. Blood was collected at 6h, 12h, 7d, 14d, 21d, and 28d after heat stress, and serum was separated. The results showed that compared with the HS group, the MTau group had significantly higher total serum protein content (P<0.05), while the other groups were not significantly different (P>0.05). The MTau and HTau groups had significantly lower serum uric acid levels than the HS group (P<0.05). At 7d and 14d, the LTau, MTau, and HTau groups all showed significantly increased T3 and T4 concentrations (P<0.05). There was no significant difference between the groups thereafter (P>0.05). Compared with HS group, the MTau group contained significantly reduced serum CK activity, LDH activity, AST activity, and ALT activity (P<0.05). In conclusion, the effects of taurine on tissue damage, protein metabolism, and basal metabolism of broilers after chronic heat stress were studied by measuring serum physiological and biochemical indices. To provide a theoretical basis for the application of taurine in acute heat-stressed broilers.

To Treat or Not to Treat? Effect of Urate-Lowering Therapy on Renal Function, Blood Pressure and Safety in Patients with Asymptomatic Hyperuricemia: A Systematic Review and Network Meta-Analysis.

Hyperuricemia is associated with increased cardiovascular risk. Because patients with asymptomatic hyperuricemia (AH) experience no immediate discomfort and there are possible side effects of urate-lowering drugs, treatment for AH is controversial. We aimed to perform a network meta-analysis (NMA) to investigate the effects of different urate-lowering therapies (ULTs) on serum uric acid level, renal function, blood pressure (BP), and safety in AH patients. This NMA focused on AH patients. The intervention group (patients receiving urate-lowering drugs) was compared with others using other types of drugs, placebo, or usual care. We undertook a NMA under the frequentist framework by R. Thirteen eligible trials were identified. The interventions included allopurinol, febuxostat, and benzbromarone, which are not approved in the United States. Benzbromarone and allopurinol had the best efficacy on lowering serum uric acid level in short-term and long-term follow-up (mean difference [MD] = -3.05; 95% CI, -5.19 to -0.91 vs MD = -3.17; 95% CI, -5.19 to -1.15). Patients using allopurinol had significantly higher eGFR than using placebo in both short-term and long-term follow-up (MD = 3.07; 95% CI, 0.18 to 5.95 vs MD = 4.10; 95% CI, 2.66 to 5.54). No difference in BP was found between groups, except for febuxostat to diastolic BP after long-term treatment (MD = -1.47; 95% CI, -2.91 to -0.04). No statistically increased odds of safety events were found with the use of ULT. Our result showed that in AH patients, allopurinol has a renoprotective effect. Febuxostat has a significant impact in lowering diastolic BP. ULT does not result in a higher risk of safety events.

A study to assess the relationship between donor uric acid levels and supernatant hemolysis in stored packed red blood cell units.

Most of the red blood cell (RBC) storage lesions can be attributed to oxidative stress encountered by the RBCs throughout the duration of their storage. Various donor variables at the time of donation may be responsible for the total antioxidant capacity of the supernatant and thus, the "storability" and the magnitude of development of these RBC storage lesions. It is known that uric acid (UA) is responsible for more than 60% of the TAC of the blood. This study aims to explore the relationship between donor UA levels and the difference in percentage hemolysis, an important RBC storage lesion, on day 1 and day 21, in stored packed RBCs (PRBCs) units. The serum UA of 100 healthy voluntary male blood donors was estimated at the time of blood donation. The percentage hemolysis in the supernatant of the leukoreduced citrate phosphate dextrose/saline-adenine-glucose-mannitol RBC units (n = 100) prepared from these donors was calculated on day 1 and day 21. The difference in percentage hemolysis between donors with high normal serum UA levels (>7 mg/dL) was compared to that of the donors with low normal serum UA levels (<5 mg/dL) to observe the effect of donor UA levels on the difference in percentage hemolysis. The mean of the differences in percentage hemolysis in the supernatant in low UA group (<5 mg/dL) was higher than the mean of the differences in percentage hemolysis in the supernatant in high UA group (>7 mg/dL) and this was statistically significant (P < 0.001). The donor serum UA level and difference in percentage hemolysis on day 21 and day 1 were found to be negatively co-related. Higher levels of serum UA of blood donors seem to have a protective effect on the stored PRBC units as shown in this study. Hence, the potential of UA as one of the constituents of RBC additive solutions might lead to the enhancement of the quality of stored PRBC units by decreasing the RBC storage lesions.

Association of serum uric acid and non-motor symptoms in Parkinson's disease: A cross-sectional study from a movement disorders clinic in Lagos, Nigeria

Background and Objective: The role of serum uric acid (SUA) as a biomarker in Parkinson's disease (PD) remains exploratory and has not been described in our population. The objective of this study was to explore the profile of SUA and its relationship to nonmotor symptoms (NMS) burden in PD. Methods: This cross-sectional study recruited 70 persons with PD and 140 matched healthy controls in Lagos, Nigeria. PD was diagnosed using the United Kingdom PD Society Brain Bank criteria. NMS were assessed with the NMS Questionnaire (NMS-Quest). SUA was measured using standard methods. Results: The mean ages of PD and controls were 63 ± 9.4 years and 62.9 ± 8.8 years, respectively (P = 0.65), with no difference when compared by sex. The median PD duration (interquartile range [IQR]) was 4 (4.25) years. Median Hoehn and Yahr stage (IQR) was 2.5 (1.0). The mean total unified Parkinson's disease rating scale score was 70.7 ± 23.7. The mean NMS-Quest score was 8.5 ± 3.8. Mean SUA level was significantly lower in PD compared to controls (2.42 ± 0.75 mg/dL vs. 3.73 ± 1.09 mg/dL [P = 0.000]). There was a nonsignificant inverse linear trend of association (r = −0.184; P = 0.126) between the total NMS-Quest score and SUA level in PD. Logistic regression analysis revealed hyposmia and memory impairment were significantly related to lower SUA levels (P = 0.02 and P = 0.04, respectively). Conclusion: Our study corroborates the potential of SUA as a serum biomarker in PD and a possible role in defining non-motor symptom burden. Further exploration to clarify the association and interrogate the impact of interventions is warranted.

Effect of Apium Graveolens (Celery) Seed Extract on Serum Uric Acid Level of Hyperuricemic Rats and its Comparison with Allopurinol

Background: Plant derived medicines are widely used in traditional culture all over the world. Objectives: To determine the effect of Celery Seed Extract (CSE) on uric acid levels in hyperuricemic rats and to compare the effect of allopurinol and CSE. Methods: It was an animal experimental research study. Group A served as negative control whereas Group B served as positive control. CSE was given orally to three groups of rats (C, D, and E). One hour prior to administration of CSE; potassium oxonate was injected intraperitoneally in all groups except negative control to induce hyperuricemia. Similarly, group F was given allopurinol one hour after injection of potassium oxonate. Blood samples were collected for uric acid estimation. Results: It was found that administration of both CSE (group C, D, E) and allopurinol (group F) significantly lowered serum uric acid levels (p&lt;0.001) as compared to positive control (group B). Serum uric acid lowering effect of both drugs CSE and allopurinol was found to be statistically significant on day 3rd and day 7th and was almost comparable. Conclusions: Celery seed extract significantly reduces serum uric acid levels in potassium oxonate-induced hyperuricemic rats and its uric acid lowering effect was comparable with that of allopurinol.

U-Shaped Association Between Serum Uric Acid Level and Hypertensive Heart Failure: A Genetic Matching Case-Control Study.

Background: Heart failure (HF) is a global pandemic and lays an added burden on public healthcare. Previous studies indicated that high and low serum uric acid levels are associated with worse outcomes in many diseases. Reduced serum uric acid may not result in a better outcome.Methods: A comparative, matched cross-sectional study design was implemented. The matching variables were age, sex, BMI, BP, and histories of CKD, CVD, diabetes mellitus, stroke, hyperlipidemia. We reviewed the electronic medical records to identify patients diagnosed with hypertension or hypertensive heart failure (HHF) admitted to Beijing Hospital's cardiology department.Results: The median age of the two groups after matching are 71. There are 55.6% males in the hypertension group and 53.8% in the heart failure group. Univariate logistic regression analysis showed that UA's quadratic term is significant (OR = 1.00, 95% CI 1.00 to 1.00; P = 0.03), which indicated a u-shaped relationship between hypertension and HHF. FBS (OR = 0.22, 95% CI 0.05 to 0.95, p = 0.07) and HDL (OR = 1.23, 95% CI 1.00 to 1.54, P = 0.05) were not significant but close.Conclusion: Our results supported that both low and high uric acid levels were predictive of hypertensive heart failure. Besides, high-density lipoprotein cholesterol and fasting blood sugar were also associated with hypertensive heart failure. Low-density lipoprotein cholesterol was not associated with hypertensive heart failure.

Melinjo seed extract stimulates intestinal ABCG2 expression to reduce serum uric acid levels in hyperuricemic rats

• We examined the association between ABCG2 and MjR in hyperuricemia rats. • ABCG2 upregulation by MjR may play an important role in decreasing serum uric acid. • Gnemonoside D was likely the main component that increases ABCG2 expression. • MjR could have potential in the treatment of hyperuricemia. Melinjo resveratrol (MjR) is a resveratrol derivative from the seed extract of melinjo ( Gnetum gnemon L.). Although it may reduce serum uric acid concentration in humans, the underlying mechanism remains unclear. Thus, we investigated the effect of MjR on the uric acid metabolism in the setting of hyperuricemia model rats induced by orally administered oxonic acid. MjR administered for three weeks significantly lowered serum uric acid levels in hyperuricemia rats. While urinary excretion of uric acid did not change, fecal excretion of uric acid significantly increased by MjR. The expression of ATP-binding cassette sub-family G member (ABCG2) was upregulated with MjR treatment in the ileum but not in the kidney. In a human epithelial colorectal cell line, Caco-2, uric acid and MjR additively stimulated ABCG2 expression. These data suggest that MjR could reduce serum uric acid by enhancing fecal excretion of uric acid in the ileum by upregulating ABCG2 protein expression.

Effects of sodium-glucose cotransporter 2 inhibitors on serum uric acid in patients with type 2 diabetes mellitus: A systematic review and network meta-analysis.

The present study aims to determine the effects of sodium-glucose cotransporter 2 (SGLT-2) inhibitors on the serum uric acid (SUA) levels of patients with type 2 diabetes mellitus (T2DM) in Asia. PubMed, CENTRAL, Embase and Cochrane Library databases were searched for randomized controlled trials of SGLT-2 inhibitors in patients with T2DM up to 15 July 2021, without language or date restrictions. In total, 19 high-quality studies (4218 participants) were included in the present network meta-analysis. All of the included SGLT-2 inhibitors (empagliflozin, dapagliflozin, canagliflozin, ipragliflozin, luseogliflozin and tofogliflozin) significantly decreased SUA levels compared with those of the control [total standard mean difference -0.965, 95% CI (-1.029, -0.901), p= .000, I2 = 98.7%] in patients with T2DM. Subgroup analysis and meta-regression showed that the combined analysis of different inhibitors might lead to heterogeneity of the results. Therefore, among the SGLT-2 inhibitors, the results of the subsequent network meta-analysis revealed that luseogliflozin and dapagliflozin ranked the highest in terms of lowering SUA levels among the SGLT-2 inhibitors. Moreover, the network meta-analysis declared that luseogliflozin (1 and 10mg) and dapagliflozin (5mg) led to a superior reduction in SUA in patients with T2DM. SGLT-2 inhibitors could significantly reduce SUA levels in patients with T2DM, particularly luseogliflozin (1 and 10mg) and dapagliflozin (5mg) possess the best effects. Therefore, SGLT-2 inhibitors look extremely promising as an antidiabetes treatment option in patients with T2DM with high SUA.

Association of Serum Uric Acid Levels in Meige's Syndrome.

Uric acid (URIC) is a natural antioxidant, and it has been shown that low levels of URIC could be a risk factor for the development of Parkinson’s disease. Our aim was to investigate whether URIC also plays a role in Meige’s syndrome (MS). We conducted a cohort study to compare serum URIC levels between patients with MS and healthy controls. In addition, we analyzed the impact of URIC on the risk of MS and symptom severity. Compared with normal subjects, URIC content was remarkably decreased in MS patients. In addition, URIC was regarded as a protective factor for MS, as verified by multivariate logistic regression models. We also found non-linear relationships between the levels of serum URIC and the incidence rate of MS and the Burke-Fahn-Marsden dystonia rating scale score. Our study is the first to show a connection between serum URIC levels and MS. Low serum URIC levels indicate an increased risk of MS incidence and more severe clinical symptoms. Our findings provide new insights into the prevention and treatment of MS.

Подагра, кардиоваскулярные риски и сердечно-сосудистые заболевания: кристаллическая неразбериха

Согласно множеству проведенных исследований подагра ассоциирована с риском развития сердечно-сосудистых заболеваний и смерти, но патогенетическая связь между этими состояниями остается не до конца детерминирована. Снижение частоты возникновения кардиоваскулярных событий при соответствующем лечении подагры свидетельствует о причинной роли этой патологии при сердечно-сосудистых заболеваниях. В обзоре рассмотрены последние исследования, посвященные взаимосвязи подагры и патологии сердечно-сосудистой системы. Исследования противоречивы: некоторые утверждают, что снижение уровня мочевой кислоты в сыворотке приводит к уменьшению риска возникновения кардиоваскулярных событий, в то время как другие не демонстрируют таких преимуществ контроля гиперурикемии. Несоответствия в дизайне исследований могут способствовать этим вариациям в результатах. Кроме того, различные стратегии лечения подагры могут повлиять на возникновение и прогрессирование заболеваний сердечно-сосудистой системы. Несмотря на значительное количество исследовательских данных, полученных за последние 15 лет, остается неясным, есть ли польза для сердечно-сосудистой системы в применении гипоурикемической терапии при подагре. Кроме того, необходимы дальнейшие исследования, чтобы уточнить преимущества тех или иных препаратов, снижающих уровень уратов, в уменьшении сердечно-сосудистых рисков. Препараты, не влияющие на уровень мочевой кислоты, но применяющиеся у пациентов с подагрой, такие как колхицин и статины, также могут улучшать исходы кардиоваскулярной патологии в этой популяции пациентов.

Lower serum uric acid level predicts mortality in dialysis patients: Erratum.

Lower serum uric acid level predicts mortality in dialysis patients: Erratum.

Relationship of medication adherence, serum uric acid level and diet to recurrent attacks of gout

Aim of the workTo evaluate the relationship between medication adherence, serum uric acid (SUA) levels, and diet, with recurrent gout attacks. Patients and methodsThis study included 89 patients being followed up for gouty arthritis. A self-administered, structured questionnaire was used to collect socio-demographic data, gout attacks frequency, history of acute intake of purine rich foods prior to the gouty attack, and adherence to urate-lowering therapies (ULT). Results89 patients were studied, 84 males and 5 females with a mean age of 55.4 ± 13.7 years, disease duration 12.22 ± 9.2 years and body mass index 24.67 ± 5.01. 71.9% were Malays, 20.2% Chinese, 6.7% Indians and 1.1% others. 61.8% had at least one episode of gout flare in the past 6 months. Of the 86 taking ULT, 65 (75.6%) were adherent. There was no difference in clinical characteristics between those who had high versus low adherence. High adherence to ULT was not associated with lower SUA or not having recurrent gout attacks. Having a high SUA level [OR = 2.86 (95%CI:1.52–5.39)], acute intake of purine-rich foods [OR = 2.01 (95%CI:1.09–3.73)] and obesity [OR = 1.58 (95%CI:1.09–2.32)] were significantly associated with recurrent gout attacks. ConclusionsAlthough three-quarters of patients were adherent to their ULT, it was not associated with a reduction in recurrent gout attacks or lower SUA levels. Recurrent gout attacks were associated with a high SUA and an acute intake of purine-rich foods. To reduce the burden of recurrent gout attacks, ULT may need to be intensified even in adherent patients, as well as avoiding dietary indiscretions.

Uric acid-lowering effect of dotinurad, a novel selective urate reabsorption inhibitor, in hypertensive patients with gout or asymptomatic hyperuricemia: a pooled analysis of individual participant data in phase II and III trials

ABSTRACT Background: Hyperuricemia is a risk factor for the development of hypertension and is comorbid in many hypertensive patients. According to Japanese hypertension management guidelines published in 2019, a target serum uric acid level of ≤6.0 mg/dL is recommended in hypertensive patients with gout or asymptomatic hyperuricemia. Dotinurad is a novel uric acid-lowering drug classified as a selective urate reabsorption inhibitor. A pooled analysis was performed on the uric acid-lowering effect of dotinurad in 222 hypertensive patients with gout or asymptomatic hyperuricemia in four clinical trials (NCT02344862, NCT02416167, NCT03100318, NCT03372200). Moreover, we analyzed the long-term uric acid-lowering effect of dotinurad in 154 hypertensive patients with gout or asymptomatic hyperuricemia (NCT03006445). Results: In the pooled analysis, the percent change in the decrease of serum uric acid with the use of dotinurad was 42.17 ± 12.42% at a dose of 2 mg and 60.42 ± 8.03% at a dose of 4 mg; the percentage of patients who achieved a serum uric acid level of ≤6.0 mg/dL was 82.8% and 100.0%. The long-term uric acid-lowering effect of dotinurad showed almost the same results. In this study, the concomitant use of diuretics or angiotensin II receptor blockers affected the uric acid-lowering effect of dotinurad at only a dose of 2 mg in the pooled analysis. Conclusions: In the pooled analysis, dotinurad lowered serum uric acid levels. Dotinurad has an achievement rate of over 80% for serum uric acid level of ≤6.0 mg/dL in both analyses, and will be clinically useful for the management of hyperuricemic states in hypertensive patients.

Low serum uric acid levels are associated with the nonmotor symptoms and brain gray matter volume in Parkinson\u2019s disease

BackgroundUric acid (UA) plays a protective role in Parkinson’s disease (PD). To date, studies on the relationship between serum UA levels and nonmotor symptoms and brain gray matter volume in PD patients have been rare.MethodsAutomated enzymatic analysis was used to determine serum UA levels in 68 healthy controls and 88 PD patients, including those at the early (n = 56) and middle-late (n = 32) stages of the disease. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. Image acquisition was performed using a Siemens MAGNETOM Prisma 3 T MRI scanner.ResultsSerum UA levels in early stage PD patients were lower than those in healthy controls, and serum UA levels in the middle-late stage PD patients were lower than those in the early stage PD patients. Serum UA levels were significantly negatively correlated with the disease course, dysphagia, anxiety, depression, apathy, and cognitive dysfunction. ROC assessment confirmed that serum UA levels had good predictive accuracy for PD with dysphagia, anxiety, depression, apathy, and cognitive dysfunction. Furthermore, UA levels were significantly positively correlated with gray matter volume in whole brain.ConclusionsThis study shows that serum UA levels were correlated with the nonmotor symptoms of dysphagia, anxiety, depression, apathy, and cognitive dysfunction and the whole-brain gray matter volume. That is the first report examining the relationships between serum UA and clinical manifestations and imaging features in PD patients.

Serum Uric Acid Level in Oral Cancer Patients -Original Study

Background Uric acid is a result of the metabolic breakdown of purine digestion. Serum uricacid ensures against carcinogenesis by means of its cell reinforcement properties and forestalls thedevelopment of oxygen extremists. High blood groupings of uric acid can prompt gout and are relatedwith diabetes and development of kidney stones. Serum uric acid fixation mirror the harmony betweenuric acid combination and discharge. Studies have indicated that high uric acid is a danger factorfor hypertension, diabetes and Cardio Vascular illness.Squamous cell carcinoma is characterized asthreatening epithelial neoplasm showing squamous separation as described by the development of keratinor the bury cell spans. It also includestheinitialpresenceofaprecancerous lesion.Moreover,specificmedicalconditionscancontributetotheoral potentially malignant disordersprevalenceOral squamous cellcarcinoma is the most well-known neoplasm speaking to over 80% of all oral malignancy cases. Serum uricacid has been proposed to be related with the danger of malignant growth and it was seen that raised degreesof serum uric acid was related with an expanded disease frequency contrasted with typical qualities.Aim and Objectives : The aim of this study is to evaluate the serum uric acid level in oral cancer patients,to find out the association between low serum uric acid level and risk of squamous cell carcinoma and tocompare the serum uric acid levels in oral cancer patients with normal individuals.Materials and Methods : This is a hospital based study to find out the uric acid level in oral cancer patients.The participants were selected from the out patients, Department of Oral Pathology and Microbiology. Thestudy included a total numbe of 28 persons. Out of the 28 persons 15 oral cancer patients were selected forthe experimental group. The remaining 13 subjects were in the normal group.Results : In this study, mean uric acid level in this stroke population with CAD is 6.37 mgs/dl and in thosewithout CAD is 5.00 mgs/dl and thus establishes a statistically significant relationship (‘p’0.0004). Whenmales and females are considered, males have a significant association with a ‘p’ value of 0.0003. The buccalmucosa of the oral cavity was the most common involved site followed by the vestibule.Conclusion : The studies showed that serum uric acid level was significantly lower in oral cancer patientscompared to the control group. Uric acid may prevent the formation of oxygen radicals and there by protectagainst carcinogenesis. In human’s uric acid is the most abundant antioxidant and is an important intracellular free radical scavenger. Early detection of oral cancer and Habit should be controlled to reducemortality rates and help to provide successful cancer treatment.

A Proposal for Practical Diagnosis of Renal Hypouricemia: Evidenced from Genetic Studies of Nonfunctional Variants of URAT1/SLC22A12 among 30,685 Japanese Individuals.

Background: Renal hypouricemia (RHUC) is characterized by a low serum uric acid (SUA) level and high fractional excretion of uric acid (FEUA). Further studies on FEUA in hypouricemic individuals are needed for a more accurate diagnosis of RHUC. Methods: In 30,685 Japanese health-examination participants, we genotyped the two most common nonfunctional variants of URAT1 (NFV-URAT1), W258X (rs121907892) and R90H (rs121907896), in 1040 hypouricemic individuals (SUA ≤ 3.0 mg/dL) and 2240 individuals with FEUA data. The effects of NFV-URAT1 on FEUA and SUA were also investigated using linear and multiple regression analyses. Results: Frequency of hypouricemic individuals (SUA ≤ 3.0 mg/dL) was 0.97% (male) and 6.94% (female) among 30,685 participants. High frequencies of those having at least one allele of NFV-URAT1 were observed in 1040 hypouricemic individuals. Furthermore, NFV-URAT1 significantly increased FEUA and decreased SUA, enabling FEUA and SUA levels to be estimated. Conversely, FEUA and SUA data of hypouricemic individuals are revealed to be useful to predict the number of NFV-URAT1. Conclusions: Our findings reveal that specific patterns of FEUA and SUA data assist with predicting the number of nonfunctional variants of causative genes for RHUC, and can also be useful for practical diagnosis of RHUC even before genetic tests.

Comparative study of a novel selective urate reabsorption inhibitor \u201cdotinurad\u201d among patient groups with different stages of renal dysfunction

BackgroundDotinurad is a selective urate reabsorption inhibitor (SURI), which selectively inhibits URAT1 to lower serum uric acid levels in patients with hyperuricemia. Herein, the effects of dotinurad were compared among patient groups with different stages of renal dysfunction.MethodsPatient data from four clinical trials were pooled and divided into four groups according to the stage of renal dysfunction to compare the effects of dotinurad at different stages. The grouping (stages G1–G3b) was based on the estimated glomerular filtration rate (eGFR) of the patients. In addition, patient data from a long-term study (34 or 58 weeks) were evaluated in the same manner.ResultsIn the pooled analysis, the percentage of patients achieving a serum uric acid level of ≤ 6.0 mg/dL was 64.7–100.0% at a dose of 2 or 4 mg. In the long-term analysis, the percentage of patients achieving a serum uric acid level of ≤ 6.0 mg/dL was 60.0–100.0% at a dose of 2 or 4 mg. Although the outcomes in stage G3b were worse due to higher baseline serum uric acid levels, satisfactory outcomes were observed in all stages. Even in stages G3a and G3b, when renal function declined, the eGFR remained constant throughout the dose period.ConclusionThe efficacy of dotinurad was confirmed in hyperuricemic patients with normal renal function (stage G1) and mild to moderate renal dysfunction (stage G2–G3b). Dotinurad was found to be effective in the treatment of hyperuricemia in patients with mild to moderate renal dysfunction.

Serum Uric Acid and Coronary Arterial Disease in Predialysis Chronic Kidney Disease Patients

Background–Aim: Uric acid is considered a marker of high cardiovascular risk. We investigated the association between serum uric acid and coronary arterial disease (CAD) in pre-dialysis chronic kidney disease (CKD) patients. Methods: We enrolled 110 subjects on mean age 69.02 ± 14.3 years old. The participants were categorized for both estimated glomerular filtration rate (eGFR) and albuminuria according to criteria 2012 of the Kidney Disease Improving Global Outcomes. Estimated pulse wave velocity (ePWV) was calculated using an equation including the age and mean blood pressure. The CAD prevalence rate was recorded. Results: The patients were divided in two groups according to uric acid cutoff point value related to high ePWV. The patients with higher uric acid were older and they had significantly higher systolic blood pressure, pulse pressure, and parathyroid hormone, but significantly lower eGFR and 1,25(OH)2 Vit D3 levels. The association between high uric acid and both high ePWV and CAD occurrence was found to be significant ( x2 = 6.7, P = .008 and x2 = 4.1, P = .03, respectively), although the relationship with albuminuria was found to be nonsignificant. In a built multifactorial model, the low serum uric acid rather than the high was found to be an independent predictor for CAD demonstration entering traditional and specific confounders. Conclusion: The low serum uric acid levels were proved to be a significant predictor for CAD accounting potential covariates, even though the high uric acid per se was found to be connected with cardiovascular disease characteristics including arterial stiffness in predialysis CKD patients.

Genetic epidemiological analysis of hypouricaemia from 4993 Japanese on non-functional variants of URAT1/SLC22A12 gene.

ObjectivesUp to 0.3% of Japanese have hypouricaemia. Most cases appear to result from a hereditary disease, renal hypouricaemia (RHUC), which causes exercise-induced acute kidney injury and urolithiasis. However, to what extent RHUC accounts for hypouricaemia is not known. We therefore investigated its frequency and evaluated its risks by genotyping a general Japanese population.MethodsA cohort of 4993 Japanese was examined by genotyping the non-functional variants R90H (rs121907896) and W258X (rs121907892) of URAT1/SLC22A12, the two most common causative variants of RHUC in Japanese.ResultsParticipants’ fractional excretion of uric acid and risk allele frequencies markedly increased at lower serum uric acid (SUA) levels. Ten participants (0.200%) had an SUA level ≤2.0 mg/dl and nine had R90H or W258X and were likely to have RHUC. Logistic regression analysis revealed these URAT1 variants to be significantly and independently associated with the risk of hypouricaemia and mild hypouricaemia (SUA ≤3.0 mg/dl) as well as sex, age and BMI, but these URAT1 variants were the only risks in the hypouricaemia population (SUA ≤2.0 mg/dl). W258X was only a risk in males with SUA ≤3.0 mg/dl.ConclusionOur study accurately reveals the prevalence of RHUC and provides genetic evidence for its definition (SUA ≤2.0 mg/dl). We also show that individuals with SUA ≤3.0 mg/dl, especially males, are prone to RHUC. Our findings will help to promote a better epidemiological understanding of RHUC as well as more accurate diagnosis, especially in males with mild hypouricaemia.