Decreased Serum Uric Acid Levels Research Articles

#2595 Evolution of hemoglobin and serum uric acid levels after SGLT2i initiation in patients with and without diabetic nephropathy

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are glucose-lowering drugs that inhibit glucose reabsorption in the proximal tubule, enhancing urinary glucose excretion. SGLT2i exhibit significant cardio- and renoprotective effects due to their capacity to increase diuresis and weight loss and reduce intraglomerular and blood pressure. Moreover, recent studies have described the potential of SGLT2i to improve additional cardiovascular risk factors, such as anemia or hyperuricemia. In this study, we aimed to describe the evolution of hemoglobin (Hb) and serum uric acid (SUA) levels in CKD patients with and without diabetic nephropathy before and after the initiation of SGLT2i therapy. Method CKD patients with and without diabetic nephropathy that were followed in the outpatient clinic of a tertiary referral academic hospital during January 2020 to September 2023 and that started SGLT2i therapy during that period were randomly recruited in the study. Patient characteristics, CKD staging, and levels of Hb and SUA before and after SGLT2i initiation were compared between groups. Hb and SUA levels were averaged considering all available laboratory controls during the last 12 months before treatment initiation and any available controls after treatment start. Results Demographic and clinical characteristics of enrolled patients are summarized in Fig. 1. Subjects with diabetic nephropathy were significantly older, more commonly hypertensive, presented worse kidney function, had received SGLT2i for a lengthier time and had lower hemoglobin values. We observed no change in hemoglobin levels after the initiation of SGLT2i in our sample, independently of diabetic nephropathy status or CKD stage (Fig. 2A, C). In contrast, SUA levels decreased significantly both in patients with and without diabetic nephropathy (Fig. 2B). This effect was observed across all the spectrum of CKD in our sample (Fig. 2D). Conclusion In our sample, SGLT2i initiation was associated with a significant decrease in SUA levels, both in patients with and without diabetic nephropathy and independently of CKD stage, which may help to explain its cardio- and nephroprotective effects. No change in Hb levels was observed, possibly due to a low prevalence of anaemia in our sample.

Nonlinear relationship between oxidative balance score and hyperuricemia: analyses of NHANES 2007–2018

BackgroundLimited data regarding the correlation between oxidative balance score (OBS) and hyperuricemia highlights the necessity for thorough investigations. This study aims to examine the link between OBS, which incorporates dietary and lifestyle factors, and the occurrence of hyperuricemia.MethodsWe conducted a cross-sectional study involving 13,636 participants from the 2007–2018 National Health and Nutrition Examination Survey (NHANES). The oxidative balance score (OBS) was determined based on four lifestyle factors and sixteen dietary nutrients. We assessed the levels of serum uric acid (SUA) and the occurrence of hyperuricemia as outcomes. Weighted logistic regression and linear models were used for statistical analysis, using Restricted Cubic Splines (RCS) to examine potential nonlinear associations. Subgroup analysis and sensitivity assessments were performed to identify any variations and ensure the robustness of the findings.ResultsHigher OBS was consistently correlated with decreased SUA levels and a reduced prevalence of hyperuricemia. RCS highlighted a significant negative nonlinear association, particularly in females. Subgroup analysis revealed gender-based differences and interactive correlation, providing additional insights regarding OBS and hyperuricemia relationship.ConclusionThis study underscores a robust negative correlation between OBS and SUA levels as well as the incidence of hyperuricemia, emphasizing the importance of dietary and lifestyle factors. Incorporating RCS, subgroup analysis, and sensitivity assessments enhances the depth of our findings, providing valuable insights for further research.

Bariatric Surgery and Its Metabolic Echo Effect on Serum Uric Acid Levels.

Bariatric surgery (BS) has been a significant means of reducing weight in obese individuals. The metabolic changes after bariatric surgery are crucial as they extend its advantages beyond weight loss. As its name implies, "metabolic surgery" also addresses obesity-related metabolic concerns. Bariatric surgery has always been associated with lessened serum uric acid (SUA) levels. In this review, we examined current studies to understand how surgical therapies impact serum uric acid levels. Strongly minded on the extent and timing of changes in the level of serum uric acid after bariatric surgeries. We conducted a comprehensive search for relevant current studies in PubMed, Google Scholar, JAMA, and the Cochrane Library until February 1, 2024. We aimed to analyze the metabolic advantages of bariatric surgery, focusing on its function in treating hyperuricemia and lowering the risk of associated disorders. Our review elaborates on factors contributing to decreased serum uric acid levels after bariatric surgery, such as alterations in renal function, insulin sensitivity, and inflammatory markers.

Baseline and change in serum uric acid level over time and resolution of nonalcoholic fatty liver disease in young adults: The Kangbuk Samsung Health Study.

To determine the association between: (i) baseline serum uric acid (SUA) level and (ii) SUA changes over time, and nonalcoholic fatty liver disease (NAFLD) resolution. A retrospective cohort study, comprising 38 483 subjects aged <40 years with pre-existing NAFLD, was undertaken. The effects of SUA changes over time were studied in 25 266 subjects. Participants underwent a health examination between 2011 and 2019, and at least one follow-up liver ultrasonography scan up to December 2020. Exposures included baseline SUA level and SUA changes between baseline and subsequent visits, categorized into quintiles. The reference group was the third quintile (Q3) containing zero change. The primary endpoint was resolution of NAFLD. During a median follow-up of 4 years, low baseline SUA level and decreases in SUA levels over time were independently associated with NAFLD resolution (p for trend <0.001). Using SUA as a continuous variable, the likelihood of NAFLD resolution was increased by 10% and 13% in men and women, respectively, per 1-mg/dL decrease in SUA. In a time-dependent model with changes in SUA treated as a time-varying covariate, adjusted hazard ratios (95% confidence intervals) for NAFLD resolution comparing Q1 (highest decrease) and Q2 (slight decrease) to Q3 (reference) were 1.63 (1.49-1.78) and 1.23 (1.11-1.35) in men and 1.78 (1.49-2.12) and 1.18 (0.95-1.46) in women, respectively. Low baseline SUA levels and a decrease in SUA levels over time were both associated with NAFLD resolution in young adults.

The effects of short term citrulline malate supplementation on oxidative stress and muscle damage in trained soccer players

There is some evidence that citrulline malate (CM) limits the deleterious effect of oxidative stress in athletes, but its effect on team sports like soccer is not clear. Thus, the current research is designed to investigate the effect of short-term CM supplementation on oxidative stress and muscle damage markers in trained soccer players. In this randomized double-blind controlled trial, 28 healthy, highly-trained male soccer players were selected and randomly assigned into 2 groups to take 6 g/day CM or placebo for 7 days. Blood samples were then taken in a resting-state at baseline and 24 h after the 7-day supplement intervention; and serum malondialdehyde (MDA), total antioxidant capacity (TAC), catalase (CAT), glutathione (GSH), superoxide dismutase (SOD), lactate dehydrogenase (LDH), creatine kinase (CK), and uric acid levels were measured. Compared to the baseline, CM significantly decreased serum uric acid levels (P = 0.03) and significantly increased serum LDH concentrations (P = 0.002). However, there were no significant changes in serum levels of MDA, CAT, GSH, TAC, SOD, LDH CK, and uric acid compared to the placebo group (P > 0.05). It appears that short-term CM supplementation does not improve oxidative stress and muscle damage in soccer players. Further investigations should be conducted to fully understand the effects of CM on soccer players.

Correlation between serum uric acid and body fat distribution in patients with MAFLD

BackgroundMetabolic dysfunction associated with fatty liver disease (MAFLD) is often correlated with obesity and hyperuricemia. The present study aimed to determine the association between serum uric acid (SUA) and central fat distribution in patients with MAFLD.MethodsA total of 485 patients were classified into the following groups: (1) controls without MAFLD and hyperuricemia (HUA), (2) MAFLD with normal SUA, and (3) MAFLD with HUA. DUALSCAN HDS-2000 was used to measure visceral fat (VAT) and subcutaneous fat (SAT). Dual-energy X-ray absorptiometry (DEXA) was used to measure body fat distribution.ResultsMAFLD patients with HUA had remarkably higher BMI, fasting insulin, OGIRT AUC, ALT, AST, TG, VAT, SAT, Adipo-IR, trunk fat mass, android fat, and total body fat than MAFLD patients with normal SUA (all p < 0.05). The increase in VAT, SAT, CAP, Adipo-IR, upper limbs fat mass, trunk fat mass, and android fat, as well as the percentage of MAFLD, were significantly correlated with the increase in SUA. The percentage of MAFLD patients with HUA increased significantly with increasing VAT or SAT, as determined by the Cochran–Armitage trend test (all p < 0.05). Furthermore, VAT (OR = 1.01 CI: 1.00, 1.03; p < 0.05) and adipo-IR (OR = 1.09 CI: 1.00, 1.19; p < 0.05) were associated with circling SUA in MAFLD after adjusting for sex, age, TG, TC, HOMA-IR, and BMI.ConclusionAbdominal fat promotes the co-existence of HUA and MAFLD, while weight loss, especially, decreasing VAT, is of great importance to decrease SUA levels and manage MAFLD.

Effects of febuxostat on markers of endothelial dysfunction and renal progression in patients with chronic kidney disease

Hyperuricemia relates to chronic kidney disease (CKD) progression and impaired endothelial function. Febuxostat is potent and effective for decreasing serum uric acid levels. Information for the effect of febuxostat treatment on markers of endothelial dysfunction and renal injury among patients with CKD remains limited. A total of 84 patients with CKD stages III-IV with asymptomatic hyperuricemia were randomly assigned to either the febuxostat (40 mg/day, N = 42) or the matching control (N = 42) group for 8 weeks. Serum asymmetric dimethylarginine (ADMA), estimated glomerular filtration rate (eGFR), urine albumin, high sensitivity C-reactive protein (hs-CRP), ankle brachial index (ABI) and serum uric acid were measured at baseline and at the end of study. Febuxostat administration significantly reduced the serum uric acid concentration among patients with CKD when compared with control [− 3.40 (95% CI − 4.19 to − 2.62) vs. − 0.35 (95% CI − 0.76 to 0.06) mg/dL; P < 0.001, respectively). No significant difference in the changes in serum ADMA, hs-CRP, eGFR and albuminuria was identified between the two groups. Subgroup analysis among patients with decreased serum uric acid after febuxostat, the estimated GFR change between the febuxostat and the control group showed significant difference at 8 weeks (2.01 (95% CI 0.31 to 3.7) vs. 0.04 (95% CI − 1.52 to 1.61) mL/min/1.73 m2; P = 0.030, respectively). Adverse events specific to febuxostat were not observed. Febuxostat effectively reduced serum uric acid in the CKD population without improving endothelial dysfunction. It was able to preserve renal function in the subgroup of patients with CKD and lower serum uric acid level after treatment.Trial registration: Thai Clinical Trials, TCTR20210224005: 24/022021 http://www.thaiclinicaltrials.org/show/TCTR20210224005.

Study on the mechanism of Orthosiphon aristatus (Blume) Miq. in the treatment of hyperuricemia by microbiome combined with metabonomics

Ethnopharmacological relevanceGrowing evidence indicates that hyperuricemia is closely associated with gut microbiota dysbiosis. Orthosiphon aristatus (Blume) Miq. (O. aristatus), as a traditional Chinese medicine, has been widely used to treat hyperuricemia in China. However, the mechanism by which O. aristatus treats hyperuricemia has not been clarified. Aim of the studyIn this study, we investigated whether the molecular mechanism underlying the anti-hyperuricemia effect of O. aristatus is related to the regulation of gut microbiota by 16S rDNA gene sequencing combined with widely targeted metabolomics. Materials and methodsHyperuricemia was induced in rats by administration of 10% fructose and 20% yeast, and the uricosuric effect was assessed by measuring the uric acid (UA) levels in serum and cecal contents. Intestinal morphology was observed by hematoxylin and eosin (HE) staining. To explore the effects of O. aristatus on the gut microbiota and its metabolites, we utilized 16S rDNA gene sequencing combined with widely targeted metabolomics. Furthermore, metabolic pathway enrichment analysis was performed on the screened differential metabolites. The real time quantitative polymerase chain reaction (RT-PCR) and western blotting (WB) were used to detect the expression of relevant proteins in the key pathway. ResultsOur results indicated that O. aristatus intervention decreased serum UA levels and increased the UA levels in cecal contents in hyperuricemic rats. Additionally, O. aristatus improved intestinal morphology and altered the composition of the gut microbiota and its metabolites. Specifically, 16S rDNA revealed that O. aristatus treatment significantly reduced the abundance of unidentified-Ruminococcaceae and Lachnospiraceae-NK4A136-group. Meanwhile, widely targeted metabolomics showed that 17 metabolites, including lactose, 4-oxopentanoate and butyrate, were elevated, while 55 metabolites, such as flavin adenine dinucleotide and xanthine, were reduced. Metabolic pathway enrichment analysis found that O. aristatus was mainly involved in purine metabolism. Moreover, RT-PCR and WB suggested that O. aristatus could significantly up-regulate the expression of UA excretion transporter ATP-binding cassette subfamily G member 2 (ABCG2) in the intestine. ConclusionO. aristatus exerts UA-lowering effect by regulating the gut microbiota and ABCG2 expression, indicating that this herb holds great promise in the treatment of hyperuricemia.

Serum Uric Acid Levels Are Related to Diabetic Peripheral Neuropathy, Especially for Motor Conduction Velocity of Tibial Nerve in Type 2 Diabetes Mellitus Patients.

Oxidative stress is one of the most critical factors that contribute to the pathogenesis of neuronal damage, including diabetic peripheral neuropathy (DPN). Uric acid is a kind of natural antioxidant that plays a major role in the antioxidant capacity against oxidative stress. Here, we aim to determine the role of serum uric acid (SUA) in the DPN of patients with type 2 diabetes mellitus (T2DM). Patients and Methods. 106 patients with T2DM were recruited and divided into the DPN group and the control group. Clinical parameters, especially for motor nerve fiber conduction velocity and sensory nerve fiber conduction velocity, were collected. Differences between T2DM patients with and without DPN were compared. Correlation and regression analyses were performed to explore the association between SUA and DPN. Compare with 57 patients with DPN, 49 patients without DPN showed lower HbA1c and elevated SUA levels. Additionally, SUA levels are negatively associated with the motor conduction velocity of tibial nerve with or without adjusting for HbA1c. Besides, it is suggested that decreased SUA levels may influence the motor conduction speed of the tibial nerve by multiple linear regression analysis. Moreover, we demonstrated that decreased SUA level is a risk factor for DPN in patients with T2DM by binary logistic regression analysis. Lower SUA is a risk factor for DPN in patients with T2DM. Additionally, decreased SUA may influence the damage of peripheral neuropathy, especially for motor conduction velocity of the tibial nerve.

Pyroglutamylproline purified from fermented barley extract increases ABCG2 expression in Caco-2 cells

Fermented barley extract P (FBEP) prepared from barley shochu distillation by-product has been reported to lower serum uric acid (UA) by increasing urinary excretion of UA. ATP-binding cassette subfamily G member 2 (ABCG2) is a transporter responsible for UA efflux from the intestinal tract and kidneys. This study aimed to identify, among the compounds isolated from FBEP using high-performance liquid chromatography, the components that promote ABCG2 expression in Caco-2 cells. Pyroglutamylproline (pEP) increased the expression of ABCG2 in Caco-2 cells at the gene and protein levels. These results suggest that the pEP contained in FBEP may decrease serum UA levels by increasing the expression of urate efflux transporters in the intestinal epithelium and promoting UA excretion.

Dietary patterns, uric acid levels, and hyperuricemia: a systematic review and meta-analysis.

Background: Studies investigating the effects of dietary intake on serum uric acid (SUA) and hyperuricemia have yielded inconsistent results. Therefore, we conducted a meta-analysis to assess the associations between various dietary patterns and SUA levels as well as hyperuricemia. Methods: We searched PubMed, Web of Science, and EMBASE databases for relevant articles examining the association between dietary intake and SUA levels and/or hyperuricemia published until March 2023. Dietary intake patterns were classified into plant-based, animal-based, and mixed dietary patterns based on predominant foods. The pooled effect sizes of eligible studies and their corresponding 95% confidence intervals (CIs) were estimated using random-effects models. Publication bias was assessed using Egger's test. Results: We included 41 studies, comprising 359 317 participants, that investigated the effects of dietary patterns on SUA levels (n = 25) and hyperuricemia (n = 19). Our findings suggested that a plant-based dietary pattern was associated with decreased SUA levels in both interventional (standard mean difference: -0.24 mg dL-1, 95% CI: -0.42, -0.06; I2 = 61.4%) and observational studies (odds ratio (OR): 0.92, 95% CI: 0.89, 0.95, I2 = 91.1%); this association was stronger in men (OR: 0.45, 95% CI: 0.35, 0.58; I2 = 0). We observed that plant- and animal-based dietary patterns were associated with a reduced risk (OR: 0.75; 95% CI: 0.67, 0.83, I2 = 93.3%) and an increased risk (OR: 1.38; 95% CI: 1.20, 1.59, I2 = 88.4%) of hyperuricemia, respectively. Conclusions: Collectively, a plant-based dietary pattern is negatively associated with SUA levels and hyperuricemia. Therefore, a plant-based dietary pattern should be recommended for the management of SUA levels and the prevention of hyperuricemia.

Decreased Serum Uric Acid Level as an Indicator of Altered Oxidative Balance in Patients With Migraine.

Migraine is one of the most common neurological diseases. The pathophysiology of migraine has not yet been fully elucidated. There is increasing evidence supporting the relationship between oxidative stress and migraine. This is a retrospective, cross-sectional and observational study. The patients were divided into two groups, episodic migraine and chronic migraine. Episodic migraine patients were divided into two subgroups, migraine with aura and migraine without aura. Serum Albumin, total bilirubin, uric acid levels, and migraine clinical findings were obtained from medical records. A total of 181 participants, 88 patients and 93 controls, were included in the study. Serum albumin levels were lower in the patient group than in the control group, they did not reach statistical significance (p=0.082). There was no significant difference between the patient and control groups for total bilirubin levels (p=0.785). Serum uric acid levels in the patient group were found to be significantly lower than in the control group (p<0.001). Measured levels were similar in chronic and episodic migraine groups, and migraine with aura and migraine without aura subgroups. We thought this oxidative stress marker may be associated with the presence of migraine, but this is not significant for migraine subtypes and migraine progression.

Associations and pathways between residential greenness and hyperuricemia among adults in rural and urban China

BackgroundResidential greenness may decrease the risk for hyperuricemia in rural areas, but the urban-rural disparities in this association and underlying pathways have not been studied. ObjectivesTo investigate the associations and potential pathways between residential greenness and hyperuricemia in urban and rural areas. MethodsThe baseline survey of the China Multi-Ethnic Cohort (CMEC) was used. Hyperuricemia was defined as serum uric acid (SUA) > 417 μmol/L for men and >357 μmol/L for women. The satellite-based normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) were used to capture residential greenness. A propensity score inverse-probability weighting method was used to assess urban-rural differences in the associations between residential greenness and hyperuricemia, with possible mediation effects of physical activity (PA), body mass index (BMI), PM2.5, and NO2 examined by causal mediation analyses. ResultsA total of 72,372 participants were included. The increases in the EVI500m and NDVI500m residential greenness were associated with a decreased risk for hyperuricemia and the SUA level in both urban and rural areas. For example, each 0.1-unit increase in EVI500m was associated with a decreased hyperuricemia risk of 7% (OR = 0.93 [0.91, 0.96]) and a decreased SUA level of −1.77 μmol/L [-2.60, −0.93], respectively; such associations were stronger in urban areas for both the risk for hyperuricemia (OR = 0.84 [0.83, 0.86]) and SUA level (−7.18 μmol/L [-7.91, −6.46]). The subgroup analysis showed that the greenness-hyperuricemia/SUA association varied by age, sex, and annual household income. The percentage of the joint mediation effect of PA, BMI, PM2.5, and NO2 on the association between EVI500m and the risk for hyperuricemia was higher in urban (34.92%) than rural areas (15.40%). BMI, PM2.5, and PA showed significantly independently mediation effects for the greenness-hyperuricemia association in both rural and urban areas. ConclusionsExposure to residential greenness was associated with a decreased risk for hyperuricemia, partially through the pathways of PA, BMI, PM2.5, and NO2, which varied in urban and rural areas.

Comparative efficacy and safety of uricosuric agents in the treatment of gout or hyperuricemia: a systematic review and network meta-analysis.

The current world witnesses a greatly increased prevalence and incidence of hyperuricemia and gout with unfortunately the comparative efficacy and safety of present available uricosuric agents remaining uncertain. We herein aimed to investigate the most appropriate uricosuric agent for gout or hyperuricemia patients. PubMed, Embase, Cochrane Library databases, and ClinicalTrials.gov from inception to 2 July 2022 were searched to retrieve eligible studies assessing efficacy and safety of uricosuric drugs in hyperuricemia or gout patients. Network meta-analysis was carried out using the Stata 16.0 software. Twelve randomized controlled trials comprising 1851 patients were eventually included. Network meta-analysis showed that dotinurad 4mg once daily, verinurad, dotinurad 2mg once daily, dotinurad 1mg once daily, and benzbromarone were the top 5 effective treatments to achieve target serum uric acid. Furthermore, dotinurad 4mg once daily was more effective at achieving urate-lowering targets (RR of dotinurad 4mg once daily vs. probenecid: 1.68, 95% CI [1.13; 2.50]) and safer (RR of probenecid vs. dotinurad 4mg once daily: 1.77, 95% CI [0.69; 4.56]) than probenecid. This network meta-analysis demonstrated an important absolute benefit of dotinurad 4mg once daily to achieve target serum uric acid and low risk of adverse events for drug treatment of gout or hyperuricemia patients. Additionally, verinurad might be used as an alternative uricosuric therapeutic option to dotinurad. These findings provided further comprehensive insight into the treatment value of current uricosuric agents for gout or hyperuricemia. Key Points 1. This is the first systematic review and network meta-analysis examining the efficacy and safety of currently available uricosuric agents in gout or hyperuricemia patients. 2. Recommended doses of dotinurad 4mg once daily used for the treatment of gout or hyperuricemia patients can significantly decrease serum uric acid levels. 3. The present findings will provide further comprehensive insight into the treatment value of certain uricosuric agents for gout or hyperuricemia.

Efficacy and Safety of Qinpi Tongfeng Formula in the Treatment of Acute Gouty Arthritis: A Double-Blind, Double-Dummy, Multicenter, Randomized Controlled Trial.

Objective Traditional Chinese medicine (TCM) has certain curative effect against acute gouty arthritis (AGA), but it lacks high-quality evidence-based studies. In this randomized controlled trial, we try to evaluate the clinical efficacy and safety of Qinpi Tongfeng Formula (QPTFF) in the treatment of AGA. Methods One hundred and fourteen patients with AGA (damp heat accumulation syndrome) who met the inclusion and exclusion criteria were randomly divided into treatment group and control group in a ratio of 1 : 1. Patients in the treatment group were treated with QPTFF, and patients in the control group were treated with diclofenac sodium sustained-release tablets for 7 days. The primary outcome measure was the change in visual analog scale (VAS) score for pain from the baseline to day 8. The secondary outcome measures were joint symptom score, TCM syndrome score, total effective rate, pain cure rate, complete pain relief time, patient satisfaction score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum uric acid level. The safety outcome measures were routine blood test, urinalysis, liver function including alanine aminotransferase and aspartate aminotransferase, renal function including blood urea nitrogen and serum creatinine, and the rate of treatment-related adverse events (TRAEs). Results 105 patients with 53 in the treatment group and 52 in the control group completed the 7-day treatment. There was no significant difference between two groups in demographic characteristics, VAS score for pain, joint symptom score, TCM syndrome score, ESR, CRP, and serum uric acid level before enrollment at baseline (based on both the full analysis set (FAS) and per protocol set (PPS), P > 0.05). The 95% confidence interval of the difference between the eighth and first VAS score for pain of the two groups was (−0.57, 0.42) in FAS and (−0.48, 0.47) in PPS. The lower bound of both FAS and PPS is greater than the bound value of −0.7. On day 8, there was no significant difference between the two groups in joint symptom score, TCM syndrome score, total effective rate, pain cure rate, complete pain relief time, patient satisfaction score, ESR, and CRP (FAS and PPS, P > 0.05). The serum uric acid level and TRAEs in the treatment group were significantly lower than those in the control group (FAS and PPS, P < 0.05). Conclusions QPTFF could alleviate the symptoms of patients with AGA, which is not inferior to diclofenac sodium sustained-release tablets in analgesic. Moreover, QPTFF overmatches diclofenac sodium sustained-release tablets in decreasing serum uric acid level and TRAEs. Therefore, the results provide reliable foundation for QPTTF in the treatment of AGA. Trial Registration. This study protocol was registered in Chinese Clinical Trial Registry (registration number: ChiCTR2100050638).

Analysis of Correlation between Hyper-Uricemia and Renal Resistivity Index in Normoglycemic Normotensive Patients

Introduction: Hyperuricemia is associated strongly with the development of renal disease and progression. Medical therapy decreases serum uric acid levels by inhibiting the enzyme xanthine oxidase. Objective of the study: To evaluate correlation of mean uric acid level and Renal Resistive Index in normoglycemic and normotensive adult subjects. Material and methods: This descriptive cross-sectional study was conducted in THQ Hospital Fort Abbas during 31-10-2018 to 30-04-2019. One hundred (n=100) non-diabetic, non-hypertensive, recently diagnosed hyperuricemic otherwise healthy subjects irrespective of gender between age 20-40 years were included in the study. After complete history taking and full physical examination laboratory testing including: serum uric acid, serum creatinine to exclude renal decompensation patients, fasting blood sugar and 2 h post prandial were advised. Results: 55.0% (n=55) of patients were males with the mean age of 33.40 years ± 3.85 SD and 45.0% (n=45) of patients were females with mean age of 34.67 years ± 3.33 SD. Cumulative mean age was 33.97 years ± 3.66 SD. The mean value of the RI of the renal arterial vasculature was 0.765 ± 0.0155 SD. The maximum, minimum and range values of the RI were 0.79, 0.74, and 0.04 respectively. The mean serum uric acid value found to be 10.947±0.562 SD. The maximum, minimum and range values of the RI were 0.79, 0.74 and 0.05 respectively. Correlation between the serum uric acid and renal arterial RI prior to the medical therapy and 3 weeks after therapy. A positive correlation was found between both values with a Pearson’s correlation coefficient = 0.103 and p-value 0.308. Conclusions: It is concluded that that medical treatment of hyperuricemia results in lowering of serum uric acid which correlates with the decrease in renal resistive index.

Effects of secukinumab and adalimumab on serum uric acid level in patients with plaque psoriasis.

Background:Psoriasis is a chronic systemic inflammatory disease, and hyperuricemia is a common comorbidity in patients with psoriasis. However, there are limited reports on the relationship between serum uric acid levels and biological treatment efficacy. The purposes of this study were to compare the differences in serum uric acid levels between patients with psoriasis and healthy controls and analyze the risk of hyperuricemia.Methods:A total of 196 patients with psoriasis and 191 age- and sex-matched healthy controls were enrolled in this retrospective cohort study. One hundred and twenty-seven patients with severe psoriasis were treated with biologics. Sixty-eight patients received adalimumab, and 59 patients received secukinumab. Serum uric acid levels were measured at baseline, week 24, and week 48 of treatment.Results:Patients with psoriasis had higher serum uric acid levels than healthy controls (6.4 ± 1.7 mg/dL vs. 5.7 ± 1.5 mg/dL, P < 0.001). Hyperuricemia was found in 33.7% (66/196) of patients with psoriasis, which was significantly higher than that in healthy controls (13.1% [25/191], P < 0.001). Serum uric acid levels and hyperuricemia were not related to the severity of psoriasis (P > 0.05). No significant changes in serum uric acid levels and hyperuricemia were observed following adalimumab treatment (P > 0.05). The serum uric acid level in patients treated with secukinumab was 6.7 ± 1.6 mg/dL at week 24, which was not statistically different from that at baseline (6.6 ± 1.4 mg/dL, P = 0.885). Serum uric acid levels were significantly decreased at week 48 (6.3 ± 1.5 mg/dL vs. 6.6 ± 1.4 mg/dL, P = 0.007) in patients treated with secukinumab. Secukinumab had no significant effect on hyperuricemia either (P > 0.05).Conclusions:The serum uric acid levels and prevalence of hyperuricemia in patients with psoriasis were significantly higher than those in healthy controls. Secukinumab treatment for 48 weeks successfully decreased serum uric acid levels in patients with psoriasis, whereas adalimumab had no significant effect on serum uric acid levels.

An integrated study of Shenling Baizhu San against hyperuricemia: Efficacy evaluation, core target identification and active component discovery

Ethnopharmacological relevanceShenling Baizhu San (SLBZ) is a famous Traditional Chinese Medicine (TCM) formula that strengthens the spleen for replenishing qi, removing dampness, and inducing diuresis to relieve diarrhea. Combining the TCM interpretation that dampness is a vital pathogenesis factor in hyperuricemia occurrence and development, SLBZ has excellent potential against hyperuricemia from the perspective of TCM theories. Aim of the studyThis study aimed to investigate the efficacy of SLBZ against hyperuricemia and its possible mechanism with emphasis on the active components and the core targets. Materials and methodsIn the present study, we employed meta-analysis and a hyperuricemia quail model to evaluate the uric acid-lowering effect of SLBZ. Bodyweight, serum uric acid, and excreta uric acid levels in quails were assessed. Subsequently, we analyzed the potential active components and core targets of SLBZ against hyperuricemia by network pharmacology and calculated their interaction using molecular docking. Furthermore, the hyperuricemia rats treated with interfering agents of core targets were established to determine the central role of selected targets in hyperuricemia progression. Besides, we isolated and characterized the primary renal tubular epithelial cells of quails to verify the active components and core targets of SLBZ against hyperuricemia. Western blotting was used to observe the expression of core targets treated with active components under the stimulation of interfering agents. ResultsData from meta-analysis and animal experiments showed that SLBZ could work effectively against hyperuricemia. Hyperuricemia quails treated with SLBZ displayed significantly reduced serum uric acid levels accompanied by increased excretion of uric acid. According to network pharmacology and molecular docking results, 34 potential active components and the core target peroxisome proliferator-activated receptor gamma (PPARγ) for SLBZ against hyperuricemia were identified. The decreased serum uric acid levels in hyperuricemia rats treated with rosiglitazone, an agonist of PPARγ, confirms the essential role of PPARγ in the pathological process of hyperuricemia. Moreover, we first successfully isolated and characterized the primary renal tubular epithelial cells of quails and observed enhanced phosphorylation of PPARγ at Ser273 in cells handled with high-level uric acid. Whereas, the enhanced expression of p-PPARγ Ser273 could be down-regulated by luteolin and naringenin, two active components of SLBZ against hyperuricemia. ConclusionIn summary, SLBZ is a promising anti-hyperuricemia agent, and luteolin and naringenin are the active components for SLBZ against hyperuricemia by down-regulating phosphorylation of PPARγ at Ser273.

Dietary 5-aminolevulinic acid supplementation improves growth performance, nutrient utilisation, iron status and antioxidant capacity of broilers

This study aimed to investigate the effects of dietary supplementation with 5-aminolevulinic acid (5-ALA) on growth performance, blood parameters, iron status, nutrient digestibility, and antioxidant capacity in broilers. A total of 600 one-day-old Arbour Acres broilers were distributed into 5 groups with 6 replicates of 20 birds by a completely randomised design. The birds in the 5 groups were fed the basal diets with 0, 15, 30, 45, and 60 mg/kg 5-ALA, respectively. Dietary supplementation with 60 mg/kg 5-ALA significantly reduced the feed to gain ratio during days 1–21 and days 22–42. Moreover, compared with the control group, dietary supplementation with 30 mg/kg 5-ALA elevated haemoglobin concentrations during days 1–21. Furthermore, dietary supplementation with 45 and 60 mg/kg 5-ALA increased the digestibility of crude protein and decreased serum uric acid levels. At 21 days of age, dietary supplementation with 45 and 60 mg/kg 5-ALA increased liver catalase activity and decreased liver malondialdehyde concentrations, and upregulated the liver mRNA expression of ferritin light chain and nuclear factor erythroid 2-related 2. In addition, the liver mRNA expression of haem oxygenase-1 and divalent metal transporter were upregulated in the 60 mg/kg 5-ALA supplementation group, while the liver mRNA expression of Kelch-like ECH-associated protein 1 was decreased in the 5-ALA supplementation groups. In conclusion, dietary supplementation with 60 mg/kg 5-ALA improved the growth performance, nutrient digestibility, iron status and antioxidant capacity of 21-d-old broilers. Highlights Addition of 60 mg/kg 5-ALA to broiler diets reduced the feed to gain ratio. Addition of 45 and 60 mg/kg 5-ALA to broiler diets improved crude protein digestibility and decreased serum uric acid levels. 5-ALA exhibited antioxidant properties by enhancing the Nrf2 and HO-1 expression

Impacts of Sodium/Glucose Cotransporter-2 Inhibitors on Circulating Uric Acid Concentrations: A Systematic Review and Meta-Analysis

Background Several trials have assessed the antihyperglycemic effects of sodium/glucose cotransporter-2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM). We conducted a quantitative analysis to assess the impact of SGLT2is on serum uric acid (SUA) in patients with T2DM. Methods Placebo-controlled trials published before 13 August 2021 were identified by searching PubMed, Embase, Web of Science, and Scopus. The intervention group received SGLT2i as monotherapy or add-on treatment, and the control group received a placebo that was replaced with SGLT2i. Clinical trials providing changes in SUA were included. The mean change of SUA, glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and body weight were calculated (PROSPERO CRD42021287019). Results After screening of 1172 papers, 59 papers were included in the systematic review. A total of 55 trials (122 groups) of 7 types of SGLT2i on patients with T2DM were eligible for meta-analysis. All SGLT2is significantly decreased SUA levels compared with the placebo groups: empagliflozin mean difference (MD) = −40.98 μmol/L, 95% CI [-47.63, -34.32], dapagliflozin MD = −35.17 μmol/L, 95% CI [-39.68, -30.66], canagliflozin MD = −36.27 μmol/L, 95% CI [−41.62, −30.93], luseogliflozin MD = −24.269 μmol/L, 95% CI [-33.31, -15.22], tofogliflozin MD = −19.47 μmol/L, 95% CI [−27.40, −11.55], and ipragliflozin MD = −18.85 μmol/L, 95% CI [−27.20, −10.49]. SGLT2i also decreased FPG, body weight, and HbA1c levels. SUA reduction persisted during long-term treatment with SGLT2i (except for empagliflozin), while the SUA reduction was affected by the duration of diabetes. Conclusions SGLT2i can be a valid therapeutic strategy for patients with T2DM and comorbid hyperuricemia. Besides reducing FPG, body weight, and HbA1c, SGLT2i can significantly decrease SUA levels compared to placebo (Total MD = −34.07 μmol/L, 95% CI [-37.00, -31.14]).