Changes In Serum Uric Acid Research Articles

A cohort study on the correlation between serum uric acid trajectory and the progression of renal function in patients with Type 2 diabetes mellitus.

Diabetic kidney disease is one of the most serious complications of diabetes mellitus (DM), and it is a main cause for chronic kidney disease and end-stage kidney disease (ESRD). It is important to find out the factors that cause the progression of renal function. The study aims to explore the relationship between serum uric acid (SUA) trajectory and the progression of renal function in patients with Type 2 diabetes mellitus (T2DM). A total of 846 patients with T2DM, who were admitted to the Department of Nephrology and Endocrinology, the Third Xiangya Hospital of Central South University, from January 2009 to December 2021 and met the criteria of baseline estimated glomerular filtration rate (eGFR)≥60 mL/(min·1.73 m2), were selected as the research subjects. The SUA data of multiple measurements were collected and identified as different SUA trajectories by group-based trajectory modeling (GBTM). According to the SUA trajectories, the patients were divided into a low trajectory group (105 cases), a middle trajectory group (396 cases), a middle high trajectory group (278 cases), and a high trajectory group (67 cases). Cox regression analysis was used to examine the effect of SUA trajectory on the progression of renal function in patients with T2DM. Subgroup analysis was performed by sex, age, course of disease, body mass index (BMI) and hemoglobin A1c (HbA1c). The median follow-up was 4.8 years. At the end of follow-up, 158 patients had different degrees of decline in renal function. After adjusting for multiple confounding factors by Cox regression analysis, the risks of eGFR<60 mL/(min·1.73 m2), eGFR reduction rate≥50%, serum creatinine (Scr) doubling and composite endpoint (eGFR reduction rate≥50%, Scr doubling or ESRD) in the high trajectory group were significantly higher than those in the low trajectory group, with HR of 3.84 (95% CI 1.83 to 8.05), 6.90 (95% CI 2.27 to 20.96), 6.29 (95% CI 2.03 to 19.52), and 8.04 (95% CI 2.68 to 24.18), respectively. There was no significant difference in the risk of ESRD among the above 4 groups (all P>0.05). Subgroup analysis showed that: compared with the low trajectory group, the risks of eGFR<60 mL/(min·1.73 m2) in patients with high trajectory in the subgroup of male, female, age<65 years, course of disease<10 years, BMI≥24 kg/m2 and HbA1c≥7% were increased (all P<0.05). The SUA trajectory had no interaction with sex, age, course of disease, BMI and HbA1c (all interactive P>0.05). The high SUA trajectory increases the risk for progression of renal function in patients with T2DM. Long-term longitudinal changes of SUA should be paid attention to.

Effects of sodium-glucose cotransporter 2 inhibitors on renal risk factors in patients with abnormal glucose metabolism: a meta-analysis of randomized controlled trials.

Several trials have assessed the antihyperglycemic effects of sodium-glucose cotransporter 2 inhibitors (SGLT2Is) in patients with type 2 diabetes mellitus (T2DM). We conducted a quantitative analysis to assess the effects of SGLT2Is on renal risk factors in patients with abnormal glucose metabolism. Randomized controlled trials (RCTs) were identified by searching the PubMed, Embase, Scopus, and Web of Science databases published before September 30, 2022. The intervention group received SGLT2Is as monotherapy or add-on treatment, and the control group received placebos, standard care, or active control. Risk of bias assessment was performed using the Cochrane risk of bias assessment tool. Meta-analysis was performed on studies with abnormal glucose metabolism populations and studies using the weighted mean differences (WMDs) as the measure of the effect size. Clinical trials providing changes in serum uric acid (SUA) were included. The mean change of SUA, glycated hemoglobin (HbA1c), body mass index (BMI), and estimated glomerular filtration rate (eGFR) were calculated. After a literature search and detailed evaluation, a total of 11 RCTs were included for quantitative analysis to analyze the differences between the SGLT2I group and the control group. The results showed that SGLT2I significantly reduced SUA (MD = -0.56, 95% CI = -0.66 ~ -0.46, I2 = 0%, P < 0.00001), HbA1c (MD = -0.20, 95% CI = -0.26 ~ -0.13, I2 = 0%, P < 0.00001), and BMI (MD = -1.19, 95% CI = -1.84 ~ -0.55, I2 = 0%, P = 0.0003). There was no significant difference in the reduction of eGFR observed in the SGLT2I group (MD = -1.60, 95% CI = -3.82 ~ 0.63, I2 = 13%, P = 0.16). These results showed that the SGLT2I group caused greater reductions in SUA, HbA1c, and BMI but had no effect on eGFR. These data suggested that SGLT2Is may have numerous potentially beneficial clinical effects in patients with abnormal glucose metabolism. However, these results need to be consolidated by further studies.

Change in Serum Uric Acid is a Useful Predictor of All-Cause Mortality among Community-Dwelling Persons.

There is limited research on the association between longitudinal variability in serum uric acid (SUA) and all-cause mortality in the general population, although recent studies have suggested that changes in SUA are associated with all-cause mortality in adults. This study aims to examine the association between percentage change in SUA (%dSUA = 100 × (cohort 2 SUA - cohort 1 SUA)/(time × cohort 1 SUA) and all-cause mortality. This study is based on 1,301 participants, of whom 543 were male (63 ± 11 years) and 758 were female (63 ± 9 years). We obtained adjusted relative risk estimates for all-cause mortality and used a Cox proportional hazards model, adjusted for possible confounders, to determine the hazard ratio (HR) and 95% confidence interval (CI) of %dSUA. Of all the participants, 79 (6.1%) were deceased, and of these, 45 were male (8.3%) and 34 were female (4.5%). The multivariable-adjusted HRs (95% CI) for all-cause mortality for the first, second to fourth (reference), and fifth %dSUA quintiles were 3.79 (1.67-8.48), 1.00, and 0.87 (0.29-2.61) for male participants and 4.00 (1.43-11.2), 1.00, and 1.19 (0.46-3.05) for female participants, respectively. Participants with a body mass index of <22 kg/m2 had a significantly higher HR, forming a U-shaped curve for the first (HR, 7.59; 95% CI, 2.13-27.0) and fifth quintiles (HR, 2.93; 95% CI, 1.05-8.18) relative to the reference. Percentage change in SUA is independently and significantly associated with future all-cause mortality among community-dwelling persons.

Changes of serum uric acid level during acute gout flare and related factors.

By studying the changes of serum uric acid (SUA) in acute stage and remission stage of gouty arthritis, we aimed to explore the relationship between the changes of SUA level and free glucocorticoids and inflammatory factors. A prospective, longitudinal study was conducted on 50 acute gout patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University. Blood and 24-hour urine samples were collected during the acute phase and two weeks after the initial visit. Patients with acute gouty arthritis were treated primarily with colchicine and nonsteroidal anti-inflammatory drugs. A total of 32 patients completed the two-week follow-up trial. SUA levels were significantly downregulated during the acute flare than after the flare (464.14 ± 90.97 vs. 527.36 ± 86.90 μmol/L, p < 0.001). The 24-hour fractional excretion of uric acid (24 h FEur) (5.54 ± 2.82% vs. 4.68 ± 2.83%, p < 0.001) and 24-hour urinary uric acid excretion (24 h Uur) (663.08 ± 249.48 μmol/L vs. 540.87 ± 263.18 μmol/L, p = 0.001) increased significantly in patients during the acute phase. The percent change in SUA was associated with those in 24 h FEur and C-reactive protein. Meanwhile, the percent change in 24 h Uur was associated with those in 24-hour urinary free cortisol, percent change in interleukin 1β and interleukin 6. Decreased SUA level during the acute gout flare was associated with increased excretion of urinary uric acid. Inflammatory factors and bioactive free glucocorticoids may play significant roles in this process.

Evaluation the effectiveness of the Jiangniaosuan formulation in the treatment of hyperuricemic nephropathy in patients with chronic kidney disease stages 3–4: Study protocol of a randomized controlled trial

BackgroundHyperuricemic nephropathy is a highly prevalent kidney disease induced by excessive accumulation and deposition of monosodium urate in kidney, which contributes to the loss of kidney function. The Jiangniaosuan formulation (JNSF) is a Chinese herbal medicine treatment. The aim of this study is to evaluate its efficacy and safety among patients with hyperuricemic nephropathy at chronic kidney disease (CKD) stages 3–4 and with obstruction of phlegm turbidity and blood stasis syndrome. MethodsOur research is designed as a single-centre, double-blinded, randomized, placebo-controlled trial for 118 patients diagnosed with hyperuricemic nephropathy at CKD stages 3–4 and with obstruction of phlegm turbidity and blood stasis syndrome in mainland China. Patients are to be randomized into two groups: either the intervention group which receives JNSF 20.4 g/day combined with febuxostat 20–40 mg/day, or the control group which receives JNSF placebo 20.4 g/day combined with febuxostat 20–40 mg/day. The intervention will be carried on for 24 weeks. The change in estimated glomerular filtration rate (eGFR) is set as the primary outcome. Secondary outcomes include changes in serum uric acid, serum nitric oxide, urinary albumin/creatinine ratio, urinary N-acetyl-β-D glucosaminidase, urinary β2 microglobulin, urinary retinol binding protein and TCM syndromes in 24 weeks. Statistical analysis will be formulated by SPSS 24.0. DiscussionThe trial will conduce to the comprehensive assessment in the efficacy and safety of JNSF among patients diagnosed with hyperuricemic nephropathy at CKD stages 3–4, and provide a clinical method available on systems of the combination of modern medicine and TCM.

Abstract 13723: Uric Acid and Treatment With Empagliflozin in Heart Failure With Preserved Ejection Fraction: The EMPEROR-Preserved Trial

Background: The sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin reduces CV death and hospitalization for HF (HHF) in patients with HF with preserved ejection fraction (HFpEF). Empagliflozin reduces serum uric acid (SUA), but the relevance of this effect in HFpEF is unclear. Methods: This post-hoc analysis of the EMPEROR-Preserved trial assessed the association between SUA and the composite primary outcome of CV death or hospitalization for worsening HF, its components and all-cause mortality (ACM) in 5,924 patients with HFpEF (98.9% of study cohort). We investigated effects of empagliflozin on SUA levels and hyperuricemic events (acute gout, gouty arthritis or initiation of anti-gout therapy), and on outcomes in relation to baseline SUA and the change in SUA levels Results: Hyperuricemia was prevalent in 49% of patients (male: 42%, female: 57%). Elevated SUA (highest tertile, mean SUA 8.8±1.4mg/dL) was associated with severity of HF and higher risk of HHF (first HHF: HR 1.42 [95%CI 1.08-1.86], recurrent HHF: HR 1.69 [95%CI 1.23-2.32], in comparison with the lowest tertile within the placebo group, both p&lt;0.01). Elevated SUA was not associated with increased CV death and ACM. Empagliflozin reduced SUA at 4 weeks (vs. placebo: -1.0±0.03mg/dL, p&lt;0.0001) and SUA remained lower throughout follow up. Empagliflozin reduced events of clinically relevant hyperuricemia by 38% (HR 0.62 [95%CI 0.51-0.76], p&lt;0.0001). The benefit of empagliflozin on the primary endpoint was independent of baseline SUA (HR 0.79 [95%CI 0.69-0.90], p=0.0007) and absolute change in SUA at 4 weeks (HR 0.87 [95%CI 0.75-1.01, p=0.07] landmark analysis). The benefit of empagliflozin versus placebo on the rate of decline of eGFR and time to first renal composite outcome was consistent across SUA tertiles (p for interaction 0.92 and 0.89, respectively) Conclusion: Hyperuricemia is common in HFpEF and is an independent predictor of disease severity and increased risk of hospitalization. Empagliflozin induced a rapid, sustained reduction of SUA levels and clinical events related to hyperuricemia. The benefit of empagliflozin on the primary outcome in HFpEF was observed independently of SUA.

Change of serum uric acid and progression of cardiometabolic multimorbidity among middle aged and older adults: A prospective cohort study.

Hyperuricemia is prevalent and associated with individual cardiometabolic diseases, highlighting the potential role of serum uric acid (SUA) in the development and progression of cardiometabolic multimorbidity (CMM, the coexistence of diabetes, heart disease, or stroke). This study aimed to examine the role of SUA change in the progression of CMM. This prospective cohort study used data from the China Health and Retirement Longitudinal Study, included 4,820 participants aged 45 years or above with three complete surveys at 2011 (baseline), 2015, and 2018. SUA level at survey 2011 and 2015 was used to measure SUA change as keeping or rising to hyperuricemia, and keeping or declining to non-hyperuricemia. CMM progression was defined as the first report of CMM or additional report of cardiometabolic diseases during survey 2015 and 2018. We used logistic regression models to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) of SUA change on CMM progression. During the follow-up of around 7 years, 519 (10.8%) of the participants kept or rose to hyperuricemia from survey 2011 to 2015, and 311 (6.5%) experienced CMM progression from survey 2015 to 2018. Participants who kept or rose to hyperuricemia had 1.86 (95% CI, 1.29, 2.68) increased odds of CMM progression compared with those who kept or declined to non-hyperuricemia. Specifically, keeping or rising to hyperuricemia (vs. keeping or declining to non-hyperuricemia) was associated with 2.01 times higher odds (95% CI, 1.18, 3.43) of incident diabetes and 1.67 times higher odds (OR:1.67; 95% CI, 1.15, 2.43) of incident cardiovascular diseases following diabetes. Keeping or rising to hyperuricemia was associated with CMM progression, particularly with incident cardiovascular diseases following diabetes. These findings suggest that monitoring SUA change may provide innovative insights into the prevention of CMM, especially in the secondary prevention of CMM (i.e., preventing further progression to cardiovascular diseases among patients with diabetes).

The urate-lowering efficacy of febuxostat and its relationship with residual renal function in peritoneal dialysis patients with hyperuricemia

Objective: To investigate the urate-lowering efficacy of febuxostat in peritoneal dialysis (PD) patients with hyperuricemia (HUA) and its relationship with residual renal function. Methods: Patients with HUA who underwent PD in Ningbo First Hospital from January 2018 to October 2021 were enrolled and divided into experimental group and control group according to whether to use febuxostat. The clinical baseline data before treatment and clinical indicators during 1-12 months after treatment were collected in two groups, and the adverse reactions during the use of febuxostat were also recorded. The changes of serum uric acid, standard-reaching rate and residual renal function were compared between the two groups during the follow-up. Results: A total of 105 patients were included in the study. There were 55 patients in the experimental group [27 males and 28 females, with a mean age of (54.5±14.8) years] and 50 patients in the control group [32 males and 18 females, with a mean age of (53.8±15.2) years]. No statistically significant difference was detected in clinical baseline data between the two groups (all P>0.05). The serum uric acid of the experimental group [(479±77), (311±69), (286±61), (307±65), (312±57) μmol/L] and control group [(486±59), (454±71), (453±76), (463±70), (459±76) μmol/L] were lower than baseline values at 1, 3, 6 and 12 months after treatment and the differences of two groups were statistically significant (all P<0.05). The serum uric acid in experimental group was significantly lower than that of control group (P<0.05). At 1, 3, 6 and 12 months after treatment, the standard-reaching rate of serum uric acid in the experimental group was significantly higher than that of the control group (all P<0.05). The decrease of residual estimated glomerular filtration rate (eGFR) and residual renal urea clearance index (Kt/V) in the experimental group were significantly lower than those in the control group at 12 months after treatment (all P<0.05). During the follow-up, the incidence of adverse reactions in the experimental group was 9.09% (5/55). Conclusions: Febuxostat can effectively treat PD patients with hyperuricemia and has a high safety profile. Moreover, it may delay the loss of residual renal function.

A follow-up study to explore factors associated with rapid kidney function decline and new-onset kidney disease among Chinese elderly population.

To explore potential factors associated with rapid kidney function decline and new-onset kidney disease among a Chinese elderly population, and to examine the relationships between baseline serum uric acid (SUA), longitudinal change in SUA and rapid estimated glomerular filtration rate (eGFR) decline over 5 years for this Chinese elderly population. A 5-year follow-up study was conducted from 2016 to 2020 in Xiamen City, China; and 2436 elderly people with normal kidney function at baseline was included. The multivariable logistic regressions were used to explore risk factors for rapid eGFR decline and new-onset kidney disease. The median age of subjects was 65 years, and 38.5% were men. These elderly people experienced a median 5-year decrease in eGFR of 14.50 mL/min/1.73 m2 , and 11.2% of them had developed new-onset kidney disease after 5-year follow-up. Participants with elevated SUA change from the normal group to the hyperuricemia group witnessed the highest decrease of eGFR after a 5-year follow-up than other groups. Multivariate analysis found advanced age, female, elevated baseline SUA, elevated SUA change, hypertension and triglyceride-glucose index were risk factors for rapid eGFR decline and new-onset kidney disease. The Chinese elderly population was more likely to encounter rapid renal function decline and new-onset kidney disease. A regular test for kidney disease was strongly recommended for these elderly people who were female, with advanced age, with elevated baseline SUA and elevated SUA change; and had high levels of insulin resistance, and blood pressure. The derived findings can offer significant evidence for targeted prevention for the Chinese elderly population. Geriatr Gerontol Int 2022; 22: 968-975.

Associations of exposure to perfluoroalkyl substances with serum uric acid change and hyperuricemia among Chinese women: Results from a longitudinal study

BackgroundCross-sectional studies have reported associations of perfluorooctanoic acid (PFOA) with concurrent serum uric acid (UA) levels. However, the prospective associations of other commonly detected perfluoroalkyl substances (PFASs) with serum UA and hyperuricemia remain unclear. MethodsA total of 654 females from the Dongfeng-Tongji cohort, who were followed up from 2008 to 2018, were included in this study. We measured their baseline plasma concentrations of six PFASs [including perfluorooctane sulfonic acid (PFOS), PFOA, perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDA), and perfluoroheptanoic acid (PFHpA)], as well as their serum UA levels at both baseline and follow-up visits. General linear and logistic regression models were constructed to explore the associations of each PFAS with annual change of serum UA and incident hyperuricemia. Mixture effects of PFASs were further assessed by using the quantile g-computation approach. ResultsCompared to participants with low PFNA exposure (≤50th), those with high PFNA exposure (>75th) had significantly increased annual increment of serum UA [β(95%CI) = 2.58 (0.60, 4.55)]. No significant associations of PFOS, PFOA, PFDA, PFHxS, or PFHpA with serum UA change were observed. Besides, females with high PFOA or PFHpA (>75th) exposure had higher incident risk of hyperuricemia than those with low exposure (<50th) [OR (95%CI) = 1.94 (1.00, 3.76) and 1.86 (1.03, 3.36), respectively]. No significant associations of PFOS, PFNA, PFDA, and PFHxS with hyperuricemia risk were observed. Quantile g-computation approach didn't find significant effects of PFAS co-exposure on serum UA change or hyperuricemia incidence. ConclusionsOur findings suggested exposure to PFASs as a risk factor for hyperuricemia and shed light on hyperuricemia prevention for elderly females.

Sodium-Glucose Cotransporter-2 Inhibitors Could Help Delay Renal Impairment in Patients with Type 2 Diabetes: A Real-World Clinical Setting.

This study compared the renoprotective effects of sodium–glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes mellitus (T2DM). We performed a retrospective cohort study using electronic medical records of patients with T2DM. The primary outcome was the first occurrence of an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 after the index date. We analyzed changes in repeatedly measured laboratory data, such as eGFR and serum uric acid (SUA). We included 2396 patients (1198 patients in each group) in the present study. The rate of renal events was significantly lower in the SGLT2 inhibitors group than that in the DPP-4 inhibitors group (hazard ratio, 0.46; 95% CI, 0.29 to 0.72; p = 0.0007). The annual mean change in the eGFR was significantly smaller in the SGLT2 inhibitors group than that in the DPP-4 inhibitors group, with a between-group difference of 0.86 ± 0.18 mL/min/1.73 m2 per year (95% CI, 0.49 to 1.23; p < 0.0001). Moreover, the mean change in SUA was lower in the SGLT2 inhibitors group. Considering the lower incidence of renal impairment, the slower decline in eGFR, and reduced SUA, SGLT2 inhibitors could help delay renal impairment in patients with T2DM.

Moderate increase of serum uric acid within a normal range is associated with improved cognitive function in a non-normotensive population: A nationally representative cohort study.

BackgroundAssociations between serum uric acid (SUA) and changes in cognitive function are understudied in non-normotensive populations, and many previous studies only considered the baseline SUA at a single time point. We aimed to examine the effects of baseline SUA and 4-year changes in SUA on cognitive changes in the non-normotensive population.Materials and methodsIn the China Health and Retirement Longitudinal Study (CHARLS), cognitive function was measured based on executive function and episodic memory in four visits (years: 2011, 2013, 2015, and 2018). We identified two study cohorts from CHARLS. The first cohort included 3,905 non-normotensive participants. Group-based single-trajectory and multi-trajectory models were applied to identify 7-year cognitive trajectories. Adjusted ordinal logistics models were performed to assess the association between baseline SUA and 7-year cognitive trajectories, and subgroup analyses were conducted according to the presence of hyperuricemia or SUA levels. The second cohort included 2,077 eligible participants. Multiple linear regression was used to explore the effect of a 4-year change in SUA on cognitive change during the subsequent 3-year follow-up.ResultsFour distinct single-trajectories of global cognitive performance and four multi-trajectories of executive function and episodic memory were identified. Higher baseline SUA levels were significantly associated with more favorable cognitive single-trajectories (ORQ4 vs. Q1: 0.755; 95% CI: 0.643, 0.900) and multi-trajectories (ORQ4 vs. Q1: 0.784; 95% CI: 0.659, 0.933). Subgroup analyses revealed that the protective effect of SUA was significant in the non-hyperuricemia groups or the low-level SUA groups. Additionally, changes in SUA could influence future cognitive changes. Compared with non-hyperuricemia participants with elevated SUA, non-hyperuricemia participants with decreased SUA and patients with persistent hyperuricemia had a higher risk for cognitive decline. Furthermore, only the Q3 group of changes in SUA could enhance global cognitive function compared with the Q1 group (β: 0.449; 95% CI: 0.073, 0.826).ConclusionOur study indicates that the maintenance of normal SUA levels and a moderate increase of SUA were advantageous in improving cognitive function or trajectories in a non-normotensive population. Conversely, SUA may impair cognitive function in patients with persistent hyperuricemia.

Temporal changes in serum uric acid and risk for metabolic syndrome: a longitudinal cohort study

BackgroundStudies suggested elevated serum uric acid (SUA) levels are associated with metabolic syndrome (MetS). However, it remains unclear whether baseline SUA and temporal changes predict MetS. The study aimed to investigate the association of baseline SUA and its temporal longitudinal changes with subsequent risk of MetS.MethodsWe conducted a retrospective longitudinal cohort study among 44,176 healthy participants aged 18 years and older without MetS at enrollment. The baseline levels and longitudinal changes of SUA were categorized by gender-specific quintiles. Participants were followed to identify newly developed MetS. We employed Cox model to investigate the relationship between SUA and MetS in men and women separately.ResultsDuring a median follow-up of 2.4 years, 5461 (12.36%) participants developed MetS. After adjustment of demographic, major clinical factors, a higher level of baseline SUA was associated with a significant higher risk of MetS. The corresponding HRs (95% CIs) comparing participants at extreme quintiles were 2.59 (2.32, 2.88) in men and 2.87 (2.41, 3.43) in women. Larger longitudinal absolute increase in SUA was also related to an increases risk of MetS (top vs bottom quintile, 1.70 [1.53, 1.89] in men and 1.94 [1.65, 2.28] in women), regardless the level of baseline SUA. Similarly, the HRs about SUA longitudinal percentage changes were 1.74 (1.56, 1.94) in men and 2.01 (1.69, 2.39) in women, respectively. Moreover, we observed the highest risk of MetS among participants with both higher baseline SUA and larger longitudinal increase in SUA.ConclusionHigher baseline SUA and larger temporal increase in SUA independently predicted risk of MetS, highlighting the importance of longitudinal SUA monitoring and management for primary prevention of MetS in the general population.

859-P: Effects of Ertugliflozin on Uric Acid and Gout-Related Outcomes: Post Hoc Analyses from VERTIS CV

The effect of ertugliflozin (ERTU) on serum uric acid (SUA) and gout-related outcomes in VERTIS CV (NCT01986881) was investigated. Patients with T2D and ASCVD were randomized to ERTU 5 mg (n=2752) , 15 mg (n=2747) (doses pooled for analyses) , placebo (PBO; n=2747) . Changes in SUA and composite of gout onset or initiation of anti-gout medication were assessed. LSM changes from baseline in SUA (mg/dL [95% CI]) at week 260 were −0. (−0.25, −0.13) and 0. (−0.02, 0.15) in the ERTU and PBO groups, respectively, nominal P&amp;lt;0.0 (Fig. 1) . The HR (95% CI) for the composite of gout-related outcomes was 0.76 (0.580, 1.002) , nominal P=0.052 (Fig. 2) . Treatment with ERTU was associated with reductions from baseline in SUA and a non-significant reduction in gout-related outcome events compared with PBO. Disclosure V.S.Sridhar: None. D.Cherney: Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research &amp; Development, LLC, Lilly, Maze, BMS, CSL-Behring, Merck, Otsuka, Novartis and Novo-Nordisk , Mitsubishi Tanabe Pharma Corporation, Sanofi, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. F.Cosentino: Advisory Panel; Merck Sharp &amp; Dohme Corp., Pfizer Inc., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Lilly, Merck Sharp &amp; Dohme Corp., Novo Nordisk. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck &amp; Co., Inc., Sanofi. R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck &amp; Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. R.Frederich: Employee; Pfizer Inc., Stock/Shareholder; Bristol-Myers Squibb Company, Pfizer Inc. M.N.Essex: Employee; Pfizer Inc., Stock/Shareholder; Pfizer Inc. M.Maldonado: Employee; Merck &amp; Co., Inc. C.Liu: Employee; Merck &amp; Co., Inc., Stock/Shareholder; Merck &amp; Co., Inc. J.P.Mancuso: Employee; Pfizer Inc., Stock/Shareholder; Pfizer Inc. Funding The VERTIS CV study and this analysis were sponsored by Merck Sharp &amp; Dohme Corp., a subsidiary of Merck &amp; Co., Inc., Kenilworth, NJ, USA, and Pfizer Inc., New York, NY, USA.

The Effects of Beta Blocker (Metoprolol) &amp; Calcium Channel Blockers (Amlodipine) on Serum Uric Acid Levels in the Patients of Hypertension

Hypertension is one of the leading health hazards which increases cardiovascular mortality and morbidity all over the world. Hyperuricemia associated with hypertension can cause the development of gout, especially in the female gender. Different antihypertensive drugs have different effects on serum uric acid levels. Aims &amp; Objective: To compare the effects of beta blockers (metoprolol) and calcium channel blocker (amlodipine) on serum uric acid level I the patients of hypertension. Methodology: This study was conducted at the Medical OPD of Bhittai Dental &amp; Medical College Mirpurkhas from July 2021 to December 2021. A total of 100 hypertensive patients were selected under inclusion and exclusion criteria and divided into two groups with equal numbers of patients. Group A patients used beta blockers (metoprolol) and group B patients used calcium channel blockers (amlodipine) for the treatment of hypertension for three months' duration. Serum uric acid was measured by the PAP uricase method before the start of treatment and after completion of the treatment research phase. Statistical analysis was done by SPSS version 22. Results: The mean serum uric acid level of male patients in group A was 7.4± 0.4 mg/dl and that of female patients in group A was 6.2± 0.1 mg/dl before the start of research. After three months of complete treatment phase, the mean serum uric acid level of male patients in group A was 7.1± 0.35 mg/dl and that of female patients in group A was 6.0 ± 0.31 mg/dl. The mean serum uric acid level of male patients in group B was 7.2± 0.38 mg/dl and that of female patients in group B was 6.1± 0.28 mg/dl before the start of research. After three months of the complete treatment phase, the mean serum uric acid level of male patients in group B was 7.0± 0.22 mg/dl and that of female patients in group B was 5.91± 0.27 mg/dl. There was no significant change in serum uric acid observed in either group under study. Conclusion: This study concluded that metoprolol (beta blocker) or amlodipine (calcium channel blocker) have no significant effect on serum uric acid levels in hypertensive patients. Keywords: Hypertension. Serum Uric Acid , Beta blockers, Calcium Channel blockers,

The Association between Baseline, Changes in Uric Acid, and Renal Failure in the Elderly Chinese Individuals: A Prospective Study with a 3-Year Follow-Up.

Objective The objective is to find whether serum uric acid (SUA) levels are associated with the progression of chronic kidney disease (CKD) remains uncertain, and follow-up data among the elderly population are relatively lacking, especially in China. The aim of the present study was to reveal the association between baseline SUA levels, changes in SUA levels, and renal failure in Chinese elderly adults. Methods In this retrospective cohort study, 425 subjects (age range 71–100 years) were analyzed and divided into quartiles based on baseline SUA levels (Q1: <4.8; Q2: <5.7; Q3: <6.5; and Q4: ≥6.5 mg/dl). CKD was defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. We used multiple linear and logistic regressions to compare the risk of renal dysfunction among the different SUA level groups. Results The prevalence of hyperuricemia was 24.24% in the elderly subjects. In the multivariable analysis, the odds ratio (OR) for the development of CKD increased with the increase in SUA quartiles at baseline (1.00 vs. 1.79 (95% CI, 1.00–3.22), 3.4 (95% CI, 1.79–6.47), and 6.79 (95% CI, 3.45–13.75), respectively; P for linear trend <0.001), and a per unit increase in baseline SUA levels gave an OR of 1.76 (95% CI, 1.45–2.14) for renal failure. At the same time, a change in SUA levels had a stronger inverse correlation with a change in eGFR in females (r = −0.318, P < 0.001) than in males (r = −0.187, P < 0.01). In a linear regression analysis, a 1 mg/dl increase in SUA levels was associated with an additional 1.25 (95% CI, −1.83 to −0.67) ml/min/1.73 m2 decrease in eGFR over a 3-year period. Conclusion Elevated baseline SUA levels and changes in SUA levels were associated with a decline in eGFR and an increased risk of CKD in an elderly Chinese population.

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]).

Changes of serum uric acid and its clinical correlation in children with dilated cardiomyopathy.

BackgroundDilated cardiomyopathy (DCM) is the most common type of childhood cardiomyopathy and uric acid (UA) is considered closely associated with cardiovascular disease. There are few reports about the relationship between serum UA level and DCM in children, and the present study aimed to analyze the changes and clinical correlation of the two.MethodsThe clinical data of 49 children under 16 years old and who were hospitalized with DCM, and 44 healthy children who underwent physical examination in the same period at Tianjin Children’s Hospital from June 2015 to November 2019 were analyzed retrospectively.ResultsThe 49 children in the case group included 17 males and 32 females, aged from 2 to 172 months. The case group were divided into New York Heart Association (NYHA) functional class I (n=2), class II (n=17), class III (n=11), and class IV (n=19). The 44 healthy children selected as the control group included 20 males and 24 females aged from 2 to 161 months. The serum UA level was detected, and an ultrasonic cardiogram was conducted in each child. The serum UA level, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and left atrial diameter (LAD) of the case group were higher than that of the control group, while the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower than that of the control group, and significant statistical differences were seen between the two groups (P<0.01). The serum UA level, LVEDD, LVESD, and LAD of NYHAIII–IV class patients were higher than that of the NYHAI–II class, but LVEF and LVFS were lower than that of the NYHA I–II class, and there were significant statistical differences between the two groups (P<0.01). Statistical correlations were seen between the serum UA level and NYHA functional class, LVEDD, LVESD, LAD, LVEF, and LVFS (rs=0.599, 0.567, 0.579, 0.475, −0.333, −0.341, respectively, P<0.05).ConclusionsElevated serum UA levels exist in children with DCM and correlate with NYHA functional class and ultrasonic values. Change in serum UA levels may be used as a biomarker reflecting the severity of DCM in children.

Serum uric acid change in relation to antihypertensive therapy with the dihydropyridine calcium channel blockers

Purpose We investigated serum uric acid changes in relation to the achieved clinic and ambulatory blood pressure after 8 weeks of antihypertensive therapy with two dihydropyridine calcium channel blockers. Materials and methods The study participants were patients with clinic and ambulatory hypertension, enrolled in a randomised controlled trial that compared amlodipine (5–10 mg, n = 215) and nifedipine gastrointestinal therapeutic system (GITS, 30–60 mg, n = 203). Hyperuricaemia was defined as a serum uric acid concentration of ≥420 µmol/L in men and ≥360 µmol/L in women. Analysis of covariance and multiple regression analyses were performed to study the associations between serum uric acid changes and the achieved clinic and ambulatory blood pressure during follow-up. Results At baseline, 67 (16.0%) of the 418 patients had hyperuricaemia. Antihypertensive treatment reduced clinic and 24-h daytime and night-time systolic/diastolic blood pressure by a mean (±standard error [SE]) change of −17.4 ± 0.6/−8.6 ± 0.4 mm Hg and −13.7 ± 0.5/−8.3 ± 0.3 mm Hg, −13.8 ± 0.6/−8.4 ± 0.4 mm Hg, and −12.7 ± 0.7/−8.0 ± 0.4 mm Hg, respectively. Antihypertensive treatment reduced serum uric acid by a mean (±SE) change of −9.3 ± 2.8 μmol/L. The serum uric acid changes differed according to the achieved clinic and ambulatory blood pressure, and were statistically significant (mean ± SE −20.6 ± 6.6 to −10.7 ± 2.9 μmol/L, p ≤ 0.04) at the systolic/diastolic ranges of 130–139/≥90 mm Hg in clinic pressure, and <130/75–84 mm Hg, <145/80–84 mm Hg and <120/65–69 mm Hg in 24-h, daytime and night-time ambulatory pressure. Conclusion Our study showed that antihypertensive therapy with a dihydropyridine calcium channel blocker was associated with reduced serum uric acid, especially when 24-h ambulatory systolic blood pressure was controlled.

Serum Uric Acid Levels and Their Changes and Risk of Stroke: A 7-Year Prospective Cohort Study in Northwest China

Introduction: It is not clear whether serum uric acid (SUA) levels and their changes over time are associated with the risk of stroke. A 7-year prospective cohort study in northwest China was conducted to analyze effects of SUA and their changes on the risk of stroke. Methods: A total of 23,262 individuals without cardiovascular disease in the Jinchang cohort were followed up for an average of 5.26 years. The Cox proportional hazard model was used to estimate the hazard ratios (HRs) and 95% confidence interval (95% CI) of stroke incidence to SUA and relative changes in SUA. Sensitivity analysis was performed after controlling the effect of renal insufficiency. Results: Baseline SUA and relative changes in SUA were positively correlated with the incidence of stroke in both males and females (p for overall association <0.0001). Stroke risk increased by 4.6% per 10% increase in the relative change of SUA (HR = 1.046, 95% CI, 1.007–1.086). The fully adjusted regression analysis demonstrated that only the large gain (>30%) in SUA was associated with an increased risk of stroke by 36.5% (95% CI, 1.8–83.0%), compared with the reference group (participants within ±10% changes in SUA). The same trend was observed in people with normal baseline SUA. In the unadjusted model, the risk of stroke associated with elevated SUA was significantly higher in the hyperuricemia group than in the normal SUA group. Conclusion: High initial SUA concentration and an increase in SUA concentration over time would increase the risk of stroke, and this means that there is no safe increase in SUA.